Ethical Considerations in Stem Cell Research and Therapy – PharmiWeb.com

Stem cell therapy is a rapidly developing field in modern medicine that holds great promise for the treatment of various diseases and injuries. Stem cells are unique cells that have the ability to develop into many different cell types in the body. They are also capable of renewing themselves through cell division, making them a valuable tool for repairing damaged tissues and organs.

Stem cell therapy involves the use of stem cells to treat or prevent diseases or conditions. These cells can be obtained from a variety of sources, including embryonic tissues, fetal tissues, and adult tissues. Once harvested, the stem cells can be manipulated in the laboratory to differentiate into specific cell types or tissues, depending on the needs of the patient.

According to The Insight Partners the stem cell therapy market is expected to grow from US$ 2,278.49 million in 2022 to US$ 6,206.89 million by 2028; it is estimated to grow at a CAGR of 18.2% from 2022 to 2028.

Applications of Stem Cell Therapy

Stem cell therapy has the potential to revolutionize the treatment of a wide range of diseases and injuries. Some of the most promising applications of stem cell therapy include:

Heart disease: Stem cell therapy has been shown to be effective in repairing damaged heart tissue in patients with heart disease. Stem cells can be used to regenerate heart muscle cells, improve blood flow to the heart, and reduce the risk of heart failure.

Parkinson's disease: Stem cell therapy may offer a promising treatment option for patients with Parkinson's disease. Stem cells can be used to generate dopamine-producing neurons, which are essential for the control of movement and coordination.

Spinal cord injury: Stem cell therapy has the potential to repair damaged spinal cord tissue and restore function to paralyzed limbs. Stem cells can be used to replace lost nerve cells and promote the growth of new connections between the brain and the body.

Diabetes: Stem cell therapy may offer a cure for type 1 diabetes by generating insulin-producing cells that can replace those that have been destroyed by the disease.

Arthritis: Stem cell therapy may offer a new approach to the treatment of arthritis by regenerating damaged cartilage tissue and reducing inflammation.

Challenges and Controversies

Despite the promising potential of stem cell therapy, there are also significant challenges and controversies associated with its use. One of the most significant challenges is the ethical considerations surrounding the use of embryonic stem cells. Embryonic stem cells are derived from embryos that are a few days old and are often obtained from in vitro fertilization clinics. Some people object to the use of embryonic stem cells because it involves the destruction of the embryo.

Another challenge is the risk of tumor formation. Stem cells have the potential to differentiate into many different cell types, including cancer cells. If stem cells are not properly controlled and regulated, they can form tumors in the patient's body.

There are also concerns about the safety and effectiveness of stem cell therapies. Many stem cell therapies are still experimental and have not been fully tested in clinical trials. Some stem cell clinics offer unproven therapies that have not been adequately tested for safety or efficacy.

Regulatory agencies such as the U.S. Food and Drug Administration (FDA) have taken steps to regulate stem cell therapies and ensure that they are safe and effective. The FDA has approved a limited number of stem cell therapies for specific indications, such as the use of bone marrow stem cells to treat certain types of cancer.

Trends in Stem Cell Therapy Industry

The field of stem cell therapy is rapidly evolving, and new developments are constantly emerging. Stem cell therapy has the potential to transform the treatment of a wide range of diseases and injuries, and as such, it is a rapidly growing industry. Here are some of the top trends in the stem cell therapy industry today:

Increased Focus on Personalized Medicine

One of the most significant trends in the stem cell therapy industry is the shift toward personalized medicine. Stem cell therapy has the potential to be tailored to the unique needs of each patient, based on their medical history, genetics, and other factors. As a result, many companies are now offering personalized stem cell therapies that are specifically designed for each individual patient.

Advancements in Stem Cell Manufacturing

Another trend in the stem cell therapy industry is the development of new manufacturing technologies that enable the production of large quantities of high-quality stem cells. Traditional methods of stem cell production, such as culturing cells in a laboratory dish, can be time-consuming and expensive. Newer methods, such as 3D printing and microfluidic devices, offer more efficient and cost-effective ways of producing stem cells.

Expansion of Stem Cell Therapy Applications

As research in stem cell therapy continues to advance, there are increasing numbers of potential applications for this technology. For example, stem cells are being explored for the treatment of conditions such as Alzheimer's disease, multiple sclerosis, and liver disease. The expansion of stem cell therapy applications is leading to increased investment in research and development, as well as greater commercialization of stem cell therapies.

Regulation and Standardization

With the increasing commercialization of stem cell therapies, there is growing concern about the need for regulation and standardization. Regulators and industry leaders are working to establish guidelines for the production, testing, and distribution of stem cell therapies. This will help to ensure that these therapies are safe, effective, and consistent.

Partnership and Collaboration

Collaboration between industry, academia, and government is crucial for the development and advancement of stem cell therapies. Many companies are forming partnerships with academic institutions and research organizations to advance the science of stem cell therapy. These collaborations are leading to greater innovation and faster progress in the field.

Gene Editing and Stem Cell Therapy

The emergence of gene editing technology, such as CRISPR-Cas9, is opening up new possibilities for the use of stem cell therapy. Gene editing allows researchers to modify the DNA of stem cells, potentially improving their safety and efficacy. This technology is also being explored for the development of new stem cell therapies that target specific genetic mutations that cause disease.

Conclusion

Stem cell therapy has the potential to revolutionize the treatment of many diseases and injuries, offering new hope to patients who have exhausted other treatment options. While there are still many challenges and controversies associated with the use of stem cells, ongoing research and clinical trials are helping to address these issues and move the field forward.

It is important for patients to be cautious when considering stem cell therapy and to consult with qualified medical professionals before undergoing any treatment. By working together, researchers, clinicians, and regulatory agencies can continue to develop and refine stem cell therapies and bring them to the patients who need them most.

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Ethical Considerations in Stem Cell Research and Therapy - PharmiWeb.com

April 2023: Intramural Papers of the Month – Environmental Factor Newsletter

IntramuralBy Janelle Weaver

A protein called double homeobox 4 (DUX4) is not only responsible for a rare muscular disease but also kills the precursors of the human nose, according to NIEHS researchers and their collaborators.

Mutations in the SMCHD1 gene can cause an extremely uncommon condition known as congenital arhinia the absence of the nose at birth. In separate sets of patients, SMCHD1 mutations sometimes lead to a late-onset neuromuscular disorder called facioscapulohumeral muscular dystrophy type 2 (FSHD2). Yet it has not been entirely clear how mutations in the same gene can result in these two highly distinct disorders.

Using human embryonic stem cells, the researchers showed that SMCHD1 mutations destroy cranial placode cells evolutionarily ancient cells that give rise to the sensory organs of the head. Specifically, SMCHD1 mutations unleash DUX4 toxicity, leading to placode cell death. Additional results revealed that induced pluripotent stem cells derived from arhinia and FSHD2 patients produce DUX4 when converting to placode cells.

Moreover, the study implicates herpesviruses, which can cause sexually transmitted diseases, as potential environmental modifiers that may exacerbate DUX4 toxicity in cranial placode cells of the developing fetus. According to the authors, more research is needed to determine why arhinia patients, but not FSHD2 patients, are characterized by abnormalities affecting the face or head.

Citation:Inoue K, Bostan H, Browne MR, Bevis OF, Bortner CD, Moore SA, Stence AA, Martin NP, Chen SH, Burkholder AB, Li JL, Shaw ND. 2023. DUX4 double whammy: the transcription factor that causes a rare muscular dystrophy also kills the precursors of the human nose. Sci Adv 9(7):eabq7744.

A cholesterol derivative called 25-hydroxycholesterol (25HC) plays dual roles in damaged lungs, according to NIEHS researchers and their collaborators.

25HC is involved in immune responses and is produced through a chemical reaction called oxidation by the enzyme cholesterol-25-hydroxylase (CH25H). Although levels of CH25H are highest in the lungs, its function in lung biology has been unclear.

Using mice with severely injured lungs, the researchers discovered that 25HC and CH25H exacerbated blood-vessel leakage and inflammation a complex biological response triggered by tissue damage. In patients with acute respiratory distress syndrome, 25HC and CH25H in lung cell and fluid samples were associated with markers of microvascular leak, inflammation, and clinical severity.

Taken together with past findings, the new results suggest that the impact of CH25H-derived 25HC depends on the extent of lung damage, with healing effects during mild inflammation but harmful effects during severe inflammation. These dual roles indicate that pharmacologic targeting of CH25H in human disease is likely to prove challenging. According to the authors, future studies are warranted to better define the functions of CH25H in the lung, and to explore whether manipulating this molecule may offer some therapeutic benefit.

Citation:Madenspacher JH, Morrell ED, McDonald JG, Thompson BM, Li Y, Birukov KG, Birukova AA, Stapleton RD, Alejo A, Karmaus PW, Meacham JM, Rai P, Mikacenic C, Wurfel MM, Fessler MB. 2023. 25-hydroxycholesterol exacerbates vascular leak during acute lung injury. JCI Insight e155448.

A protein called GLI-Similar 3 (GLIS3) coordinates with three other proteins to synthesize thyroid hormone, according to NIEHS researchers and their collaborators.

Congenital hypothyroidism is thyroid-hormone deficiency present at birth. Severe forms of the disease can lead to growth failure and permanent intellectual disability. In both humans and mice, congenital hypothyroidism is triggered by loss of GLIS3 function because this protein plays a critical role in the production of thyroid hormone. Yet it has not been clear how GLIS3 teams up with other proteins called transcription factors to regulate the expression of thyroid genes.

Using rodent thyroid glands and cells, the researchers showed that GLIS3 works in conjunction with three protein partners paired box 8 (PAX8), NK2 homeobox 1 (NKX2.1), and forkhead box E1 (FOXE1). All of these proteins control the transcription of genes involved in thyroid hormone synthesis by binding within the same regulatory hub in these genes.

But GLIS3 does not affect the binding of PAX8 or NKX2.1 to thyroid genes. In addition, GLIS3 does not appear to alter transcription by causing major changes in the structure of chromatin a DNA-protein complex that forms chromosomes. According to the authors, future studies could establish whether GLIS3 has any effect on chromatin structure, or how the protein might otherwise activate thyroid genes.

Citation:Kang HS, Grimm SA, Jothi R, Santisteban P, Jetten AM. 2023. GLIS3 regulates transcription of thyroid hormone biosynthetic genes in coordination with other thyroid transcription factors. Cell Biosci 13(1):32.

Exposure to nicotine protects the mouse brain from developing certain signs of infection and disease related to severe acute respiratory syndrome coronavirus 2 (SARSCoV2), according to NIEHS researchers and their collaborators. These results suggest the biological targets of nicotine could be harnessed to help individuals avoid long COVID.

SARS-CoV-2 is the virus that causes coronavirus disease 2019 (COVID-19), which has killed more than six million people worldwide. Individuals infected with SARS-CoV-2 are at risk of developing a neurological disorder known as long COVID. Symptoms of the disease include cognitive dysfunction, loss of smell, sleep disturbances, headaches, dizziness, fatigue, muscle pain, anxiety, and depression.

Even mild cases can change the structure of the brain, but knowledge of the mechanisms and risk factors that enable SARS-CoV-2 to affect the central nervous system is lacking. Disputed epidemiological data suggest that nicotine may reduce the severity of infection. Yet the possible therapeutic effects of nicotine have not been clear.

To address this knowledge gap, the researchers inoculated mice with SARS-CoV-2 and then provided some of them with a nicotine solution instead of drinking water. Nicotine intake did not alter death rates, but it decreased viral RNA and signs of disease in the brains of a subset of infected mice. According to the authors, the findings could be leveraged to prevent or mitigate neurological-related disorders caused by SARS-CoV-2.

Citation:Letsinger AC, Ward JM, Fannin RD, Mahapatra D, Bridge MF, Sills RC, Gerrish KE, Yakel JL. 2023. Nicotine exposure decreases likelihood of SARS-CoV-2 RNA expression and neuropathology in the hACE2 mouse brain but not moribundity. Sci Rep 13(1):2042.

The herbicide glyphosate does not appear to pose a hazard to human DNA, according to researchers from the NIEHS Division of Translational Toxicology.

Over the past 30years, glyphosate has become the most commonly used herbicide in the United States and throughout the world. Past research has suggested that glyphosate and glyphosate-based formulations (GBFs) may damage DNA (i.e., cause genotoxicity), raising concern about their potential health risks, including cancer. But few of these studies directly compared glyphosate to GBFs or effects among GBFs. Chemicals and other substances are routinely tested for genotoxicity because damage to DNA increases the risk of cells becoming cancer cells.

To address this knowledge gap, the researchers tested how human cells are affected by exposure to glyphosate, a microbial metabolite of glyphosate called (aminomethyl)phosphonic acid (AMPA), various GBFs, and additional herbicides. Neither glyphosate nor AMPA appeared to be toxic, even at high concentrations. By contrast, all GBFs and herbicides other than glyphosate injured the cells, and some of these chemicals damaged DNA. Additional analyses suggested that glyphosate is of low toxicological concern for humans.

The observation that glyphosate is not genotoxic in human cells aligns with the National Toxicology Programs previous findings, published in 1992, that glyphosate was not genotoxic to mice exposed up to 50,000 ppm glyphosate in their food for three months.

Taken together, these results demonstrate that glyphosate does not produce DNA damage in the form of gene mutations, chromosome breaks, or changes in chromosome number, and that cytotoxicity (i.e., cell death) associated with GBFs may be related to other components of these formulations. For example, ingredients such as surfactants and detergents may compromise cell membranes or otherwise lead to cell death.

Citation:Smith-Roe SL, Swartz CD, Rashid A, Christy NC, Sly JE, Chang X, Sipes NS, Shockley KR, Harris SF, McBride SJ, Larson GJ, Collins BJ, Mutlu E, Witt KL. 2023. Evaluation of the herbicide glyphosate, (aminomethyl)phosphonic acid, and glyphosate-based formulations for genotoxic activity using in vitro assays. Environ Mol Mutagen; doi: 10.1002/em.22534 [Online 7 March 2023].

(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)

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April 2023: Intramural Papers of the Month - Environmental Factor Newsletter

Brain molecule could reverse damage in multiple sclerosis, U of A … – The Gateway Online

Multiple sclerosis (MS) is a chronic neurodegenerative disease in which demyelination occurs. Demyelination is where the myelin or fatty lining of a neuron erodes, leading to damage in the central nervous system.

Over 90,000Canadians are affected by MS. It can cause bodily impairment ranging from blurred vision, to complete lack of muscle coordination and paralysis. Anastassia Voronova, an assistant professor at the University of Alberta and Canada research chair in Neural Stem Cell Biology, has done research on how to reverse demyelination.

In her research, published in Stem Cell, Voronova has discovered a way to target remyelination. This involves direct infusion of the brain molecule, fractalkine, which triggers the production of myelin.

She dietarily induced demyelination in the brains of mice to mimic the brain damage apparent in MS patients. She then injected fractalkine directly into their brains. The molecule consequently enhanced remyelination in the white and gray matter areas of the brain, despite experiencing damage from MS.

Fractalkine triggers progenitor cells descendants of stem cells which can create specialized cell types in the brain to make new oligodendrocytes, which are the only brain cells that produce myelin. It also lessens neuroinflammation common in MS.

Both of these events are necessary for the enhancement of remyelination by fractalkine, which Voronova said is predicted to halt the disease progression, and maybe even reverse some of the neurological symptoms that are associated with MS.

Voronova described the existing progenitor cells as lazy. They should know how to regenerate oligodendrocytes for remyelination, but are inefficient especially in MS patients.

Myelin deficiencies are detected in a variety of neurological disorders, such as Huntingtons, Parkinsons, and Alzheimers disease. Myelin deficiencies can also be found in neurodevelopmental disorders, including autism, schizophrenia, epilepsy, and traumatic brain injuries.

What we are also excited about is whether we can test the ability of fractalkine to promote brain regeneration in mouse models of other neurological disorders. Maybe this could be translated to a variety of different conditions, and not just something specific for MS, Voronova said.

Voronova and her research team are searching for ways to deliver fractalkine to the brain, such as a nasal spray.

Fractalkine is the molecule of interest in her recent study. But, Voronovas research program aims to discover new molecules that can trigger progenitor cells to cause brain regeneration.

Stem cells are set aside during embryonic brain development. But, they do not have a fixed function and are otherwise dormant throughout adulthood. The question of whether it is possible to resurrect embryonic cues in adult stem cells for use in neural regeneration drives Voronovas research.

This was actually a serendipitous discovery I started my journey in science by asking how do stem cells behave during brain development?

Voronova wanted to understand how neural stem cells communicate with neurons in close proximity within the developing brain.

I discovered that these neurons were secreting so many different molecules including fractalkine that then instructed the neural stem cells to make oligodendrocytes in the developing brain, she said.

Now my research program is built on translating this developmental discovery to engage the adult neural stem cells for brain regeneration.

The process of reactivating these embryonic cues remains unknown, but Voronova is making progress with her research.

I think it was 30 years ago it was realized that we have adult neural stem cells. We didnt know what they were doing there. And now, I think we definitely understand their promise. But, we dont necessarily understand how to harness the promise, Voronova said.

Its learning the signalling molecules and signalling pathways that were once important in the embryonic [stages] of brain development and then seeing whether I can reactivate those same signalling pathways in the adult brain, as well.

Every year,The Gatewaypublishes hundreds of articles like the one you just read that are free for everyone to access. ButThe Gatewayneeds your support to continue publishing its award-winning journalism. Please consider donating today, even a small amount can help the University of Albertas only newspaper continue serving the campus community. Thank you.

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Brain molecule could reverse damage in multiple sclerosis, U of A ... - The Gateway Online

INTERNATIONAL STEM CELL CORP MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) – Marketscreener.com

The following discussion of our financial condition and results of operationsshould be read in conjunction with our audited consolidated financial statementsand related notes and other financial information included elsewhere in thisAnnual Report on Form 10-K. The discussion contains forward-looking statements,such as our plans, expectations and intentions (including those related toclinical trials and business and expense trends), that are based upon currentexpectations and that involve risks and uncertainties. Our actual results maydiffer significantly from management's expectations. The factors that couldaffect these forward-looking statements are in Item 1A of Part I of this report.This discussion should not be construed to imply that the results discussedherein will necessarily continue into the future, or that any expectationsexpressed herein will necessarily be indicative of actual operating results inthe future. Such discussion represents only the best present assessment by ourmanagement.

Business Overview

We have generated aggregate product revenues from our two commercial businessesof $8.2 million and $7.2 million for the years ended December 31, 2022 and 2021,respectively. We currently have no revenue generated from our principaloperations in therapeutic and clinical product development.

Our products are based on multi-decade experience with human cell culture and aproprietary type of pluripotent stem cells, human parthenogenetic stem cells("hpSCs"). Our hpSCs are comparable to human embryonic stem cells ("hESCs") inthat they have the potential to be differentiated into many different cells inthe human body. However, the derivation of hpSCs does not require the use offertilized eggs or the destruction of viable human embryos and also offers thepotential for the creation of immune-matched cells and tissues that are lesslikely to be rejected following transplantation. Our collection of hpSCs, knownas UniStemCell, currently consists of 15 stem cell lines. We have facilitiesand manufacturing protocols that comply with the requirements of GoodManufacturing Practice (GMP) standards as promulgated by the U.S. Code ofFederal Regulations and enforced by the United States Food and DrugAdministration ("FDA").

COVID-19 Pandemic

The impact of the COVID-19 pandemic has been and will likely continue to beextensive in many aspects of society, which has resulted in and will likelycontinue to result in significant disruptions to the global economy, as well asbusinesses and capital markets around the world. Impacts to our business haveincluded a reduction in sales volume primarily from media sales in ourbiomedical market segment and professional channel sales in our anti-agingmarket segment, temporary or reduced occupancy of portions of our manufacturingfacilities, and disruptions or restrictions on our employee's ability to travelto such manufacturing facilities which caused minor delays in manufacturing. Wehave taken precautionary measures to better ensure the health and safety of ourworkers.

The scope and duration of these delays and disruptions, and the ultimate impactsof COVID-19 on our operations, are currently unknown. We are continuing toactively monitor the situation and may take further precautionary and preemptiveactions as may be required by federal, state or local authorities or that wedetermine are in the best interests of public health and safety. We cannotpredict the effects that such actions, or the impact of COVID-19 on globalbusiness operations and economic conditions, may continue to have on ourbusiness, strategy, collaborations, or financial and operating results.

Market Opportunity and Growth Strategy

Therapeutic Market - Clinical Applications of hpSCs for Disease Treatments

We believe that the most promising potential clinical applications of ourtechnology are Parkinson's disease ("PD"), traumatic brain injury ("TBI"), andstroke. Using our proprietary technologies and know-how, we are creating neuralstem cells from hpSCs as a potential treatment of PD, TBI, and stroke.

PD: Our most advanced project is the neural stem cell program for the treatmentof Parkinson's disease. In 2013, we published in Nature Scientific Reports thebasis for our patent on a new method of manufacturing neural stem cells, whichis used to produce the clinical-grade cells necessary for future clinicalstudies and commercialization. In 2014, we completed the majority of thepreclinical research, establishing the safety profile of NSC in various animalspecies, including non-human primates. In June 2016, we published the results ofa 12-month pre-clinical non-human primate study, which demonstrated the safety,efficacy and mechanism of action of the ISC- hpNSC. In 2017, we dosed fourpatients in our Phase I trial of ISC-hpNSC, human parthenogenetic stemcell-derived neural stem cells for the treatment of Parkinson's disease. Wereported 12-month results from the first cohort and 6-month interim results ofthe second cohort at the Society for Neuroscience annual meeting (Neuroscience2018) in November 2018. In April 2019, we announced

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the completion of subject enrollment, with the 12th subject receiving atransplantation of the highest dose of cells. There have been no safety signalsor serious adverse effects seen to date as related to the transplantedISC-hpNSC cells.

We announced a successful completion of the dose escalating phase 1 clinicaltrial in June 2021. In terms of preliminary efficacy, where scores are comparedagainst baseline before transplantation, we observed a potential dose-dependentresponse with an apparent peak effectiveness at our middle dose. The % OFF-Time,which is the time during the day when levodopa medication is not performingoptimally and PD symptoms return, decreased an average 47% from the baseline at12 months post transplantation in cohort 2. This trend continued through 24months where the % OFF-Time in the second cohort dropped by 55% from the initialreading. The same was true for % ON-Time without dyskinesia, which is the timeduring the day when levodopa medication is performing optimally withoutdyskinesia. The % ON-Time increased an average of 42% above the initialevaluation at 12 months post-transplantation in the second cohort.

Stroke: In August 2014, we announced the launch of a stroke program, evaluatingthe use of ISC-hpNSC transplantation for the treatment of ischemic stroke usinga rodent model of the disease. The Company has a considerable amount of safetydata on ISC-hpNSC from the Parkinson's disease program and, as there isevidence that transplantation of ISC-hpNSC may improve patient outcomes as anadjunctive therapeutic strategy in stroke, having a second program that can usethis safety dataset is therefore a logical extension. In 2015, the Companytogether with Tulane University demonstrated that NSC can significantly reduceneurological dysfunction after a stroke in animal models.

TBI: In October 2016, we announced the results of the pre-clinical rodent study,evaluating the use of ISC-hpNSC transplantation for the treatment of TBI. Thestudy was conducted at the University of South Florida Morsani College ofMedicine. We demonstrated that animals receiving injections of ISC-hpNSCdisplayed the highest levels of improvements in cognitive performance and motorcoordination compared to vehicle control treated animals. In February 2019, wepublished the results of the pre-clinical study in Theranostics, a prestigiouspeer-reviewed medical journal. The publication titled, "Human parthenogeneticneural stem cell grafts promote multiple regenerative processes in a traumaticbrain injury model," demonstrated that the clinical-grade neural stem cells usedin our Parkinson's disease clinical trial, ISC-hpNSC, significantly improvedTBI-associated motor, neurological, and cognitive deficits without any safetyissues.

Anti-Aging Cosmetic Market - Skin Care Products

Our wholly owned subsidiary Lifeline Skin Care, Inc. ("LSC") develops,manufactures, and sells anti-aging skin care products based on two coretechnologies: encapsulated extract derived from hpSC and specially selectedtargeted small molecules. LSC's products include:

ProPlus Advanced Defense Complex

ProPlus Advanced Recovery Complex

ProPlus Advanced Aqueous Treatment

ProPlus Collagen Booster (Advanced Molecular Serum)

LSC's products are regulated as cosmetics. LSC's products are sold domesticallythrough a branded website, Amazon, and ecommerce partners.

Biomedical Market - Primary Human Cell Research Products

Our wholly-owned subsidiary LCT develops, manufactures and commercializesapproximately 200 human cell culture products, including frozen human "primary"cells and the reagents (called "media") needed to grow, maintain anddifferentiate the cells. LCT's scientists have used a standardized, methodical,scientific approach to basal medium optimization to systematically produceoptimized products designed to culture specific human cell types and to elicitspecific cellular behaviors. These techniques can also be used to produceproducts that do not contain non-human animal proteins, a feature desirable tothe research and therapeutic markets. Each LCT cell product is quality testedfor the expression of specific markers (to assure the cells are the correcttype), proliferation rate, viability, morphology and absence of pathogens. Eachcell system also contains associated donor information and all informed consent

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requirements are strictly followed. LCT's research products are marketed andsold by its internal sales force, OEM partners and LCT brand distributors inEurope and Asia.

Results of Operations

Comparison of the Years Ended December 31, 2022 and 2021

General and administrative 3,357 4,084 (727 ) -18 %Selling and marketing 1,245 1,383 (138 ) -10 %Research and development 492 695 (203 ) -29 %Other income (expense), net (148 ) 1,022 (1,170 ) -114 %Net loss

Product sales revenue for the year ended December 31, 2022 was $8,180 thousand,compared to $7,176 thousand for the year ended December 31, 2021. The increasewas primarily attributable to a $1,195 thousand increase in sales in ourbiomedical market segment, largely offset by a $191 thousand decrease in salesin our anti-aging market during 2022 compared to 2021.

Our biomedical product sales continue to recover from the impacts of COVID-19 aspurchasing activity from our original equipment manufacturer customers accountfor approximately 86% of the increase in this market segment.

Our professional line of anti-aging products was discontinued starting in 2022resulting in only one product line and less demand. The products that werelargely marketed to medical professionals and spas that offered walk-up retail,experienced a significant decline in customer demand due to COVID-19 and therelated restrictions during the year ended December 31, 2021. The impact ofshutting down to one line has been partially mitigated by our expanded offeringof professional skin care products through our ecommerce channel. Anti-agingproduct sales through our ecommerce channel decreased slightly year-over-year.

Cost of Sales

Cost of sales for the year ended December 31, 2022 was $3,269 thousand, comparedto $2,935 thousand for the year ended December 31, 2021. There was an increasein cost of sales as a result of the increase in product sales in our biomedicalmarket segment of $589 thousand; however, this was offset by significantfavorable manufacturing variances due to the increased sales volumes resultingin a net increase of $172 thousand year over year. There also was an increase incost of goods sold in our anti-aging market of approximately $162 thousand, netprimarily attributable to large amounts of expired product reserves booked as aresult of the change in sales channel and lines of business from 2021 to 2022.In response to previous material scarcities primarily in plastics, we haveincreased our supply of raw materials on hand and have, where possible, sourcedmaterials from alternative vendors.

Cost of sales consists primarily of salaries and benefits associated withemployee efforts expended directly on the production of the Company's products,as well as related direct materials, general laboratory supplies and anallocation of overhead. We aim to continue refining our manufacturing processesand supply chain management to improve the cost of sales as a percentage ofrevenue for both LCT and LSC.

General and Administrative Expenses

General and administrative expenses for the year ended December 31, 2022 was$3,357 thousand, compared to $4,084 thousand for the year ended December 31,2021. The decrease was primarily attributable to a decrease in personnel-relatedcosts including stock-based compensation, human resources, workers compensationand relocation expenses of $385 thousand, a $250 thousand decrease in patentimpairment charges, $124 thousand decrease in building expenses, $49 thousanddecrease in computer and amortization expenses,

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and $60 thousand in legal and directors and officers insurance fees decreases,partially offset by $134 thousand increase primarily in consulting and servicingfees.

Our general and administrative expenses consist primarily of employee-relatedexpenses including salaries, bonuses, benefits and share-based compensation.Other significant costs include facility costs not otherwise included in orallocated to other departments, legal fees not relating to patents and corporatematters, and fees for accounting and consulting services.

Selling and Marketing Expenses

Selling and marketing expenses for the year ended December 31, 2022 was $1,245thousand, compared to $1,383 thousand for the year ended December 31, 2021. Thedecrease was primarily attributable to a $69 thousand decrease inpersonnel-related costs, sales commissions, stock-based compensation andconsultant costs, primarily as a result of headcount reductions and changes inour anti-aging segment year over year. There was a decrease of approximately $16thousand from dues and subscriptions, licensing and other merchant fees, andapproximately $35 thousand decrease in building and other expenses. The decreasewas partially offset by an increase of $61 thousand in marketing materials andwebsite and search engine maximization advertising expense.

Our sales and marketing expenses consist primarily of employee-related expensesincluding salaries, bonuses, benefits, and share-based compensation for ourBiomedical and Anti-aging cosmetic businesses. Other significant costs includefacility costs not otherwise included in or allocated to other departments aswell as marketing material costs, permits and licenses for ecommerce, and otheradvertising type expenses.

Research and Development Expenses

Research and development expenses for the year ended December 31, 2022 was $492thousand, compared to $695 thousand for the year ended December 31, 2021. Thedecrease was primarily attributable to $168 thousand decrease in buildingrelated expenses, $73 thousand decrease in consulting services, $54 thousanddecrease in material, supplies and licensing related expenses partially offsetby $50 thousand in personnel-related costs and stock-based compensation as aresult of increased salaries in Research and Development after salary raisefreezes during the pandemic and $42 thousand decrease in our Australian researchand development tax credit related to qualifiable expenditures from our researchand development activities of our Australian subsidiary, Cyto Therapeutics.

Our research and development efforts are primarily focused on the development oftreatments for Parkinson's disease, traumatic brain injury, liver diseases,stroke, and the creation of new GMP grade human parthenogenetic stem cell lines.These projects are long-term investments that involve developing both new stemcell lines and new differentiation techniques that can provide higher puritypopulations of functional cells. Research and development expenses are expensedas incurred and are accounted for on a project-by-project basis. However, muchof our research has potential applicability to each of our projects.

Other Income (Expense), Net

Other income, net, for the year ended December 31, 2022 was a loss of $148thousand, compared to other income, net, of $1,022 thousand for the year endedDecember 31, 2021. The decrease was primarily attributable to the gainrecognized on the forgiveness of debt related to our First and Second Draw Loanunder the PPP, collectively totaling $1,137 thousand in 2021. The remainder ofthe difference relates to accrued interest on outstanding debt.

Liquidity and Capital Resources

The Company enters into contracts in the normal course of business with variousthird-party consultants and contract research organizations ("CRO") forpreclinical research, clinical trials and manufacturing activities. Thesecontracts generally provide for termination upon notice. Actual expensesassociated with these arrangements may be higher or lower due to variousreasons, including but not limited to, progress of our development products,enrollment in clinical trials, and product and personnel delays due to COVID.Other short-term and long terms commitments that would affect liquidity includelease obligations as well as related party debt repayments.

As of December 31, 2022, we had an accumulated deficit of approximately $110.3million and have, on an annual basis, incurred net losses and negative operatingcash flows since inception. Substantially all of our operating losses haveresulted from the funding of our research and development programs and generaland administrative expenses associated with our operations. We incurred netlosses of $331 thousand and $899 thousand for years ended December 31, 2022 and2021, respectively. As of December 31, 2022, we had cash of $742 thousand,compared to $171 thousand as of December 31, 2021.

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Licensed Patents

The Company had a minimum annual license fee of $75 thousand payable in twoinstallments per year to Astellas Pharma pursuant to the amended UMass IPlicense agreement. The patents, along with the license agreement, expired at theend of July 2022. These patents were fully impaired in prior years and thereforethe expiration did not result in any additional impairment for the year endedDecember 31, 2022. The Company does not anticipate any short-term liquidityeffects from this obligation as we will no longer be liable for the annuallicensing fee.

Cash Flows

Comparison of the Years Ended December 31, 2022 and 2021

The following table provides information regarding our cash flows for the yearsended December 31, 2022 and 2021 (in thousands):

Net cash provided by (used in) operating activities $ 332 $ (1,297 )Net cash used in investing activities

Operating Cash Flows

For the year ended December 31, 2022, net cash provided by operating activitieswas $332 thousand, resulting primarily from our net loss of $331 thousand, andnet changes in operating assets and liabilities of $226 thousand, consistingprimarily of an increase in accrued liabilities of $104 thousand, inventory,net, of $114 thousand, and decrease in accounts payable of $186 thousand andoperating lease liabilities of $179 thousand. The decrease in cash is offset bynet recurring non-cash adjustments of $890 thousand, including depreciation andamortization, stock-based compensation, operating lease expense, and interestexpense. For the year ended December 31, 2021, net cash used in operatingactivities was $1,297 thousand, resulting primarily from our net loss of $899thousand and gain on forgiveness of debt of $1,137 thousand, offset by non-cashadjustments of stock-based compensation expense of $644 thousand, operatinglease expense of $289 thousand, and depreciation and amortization of $262thousand, coupled with net changes in operating assets and liabilities of $823thousand.

Investing Cash Flows

Net cash used in investing activities for the year ended December 31, 2022 was$11 thousand, compared to $45 thousand for the year ended December 31, 2021. Thedecrease was attributable to a decrease in payments for patent licenses of $12thousand and net decrease in the purchases of property and equipment of $22thousand year-over-year.

Financing Cash Flows

Net cash provided by financing activities for year ended December 31, 2022 was$250 thousand, compared to $824 thousand for the year ended December 31, 2021.For the year ended December 31, 2022, net cash provided by financing activitiesconsisted of $250 thousand in proceeds from a note payable from a related party.For the year ended December 31, 2021, net cash provided by financing activitiesconsisted of $474 thousand in proceeds from our second draw loan under thePaycheck Protection Program, coupled with proceeds from a note payable from arelated party of $350 thousand.

Liquidity and Going Concern

Management continues to evaluate various financing sources and options to raiseworking capital to help fund our current research and development programs andoperations. We will need to obtain significant additional capital from sourcesincluding exercise of outstanding warrants, equity and/or debt financings,license arrangements, grants and/or collaborative research arrangements tosustain our operations and develop products. Unless we obtain additionalfinancing, we do not have sufficient cash on hand to sustain our operations atleast through one year after the issuance date. The timing and degree of anyfuture capital requirements will depend on many factors, including:

the accuracy of the assumptions underlying the estimates for capital needs in2023 and beyond;

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the extent that revenues from sales of LSC and LCT products cover the relatedcosts and provide capital;

scientific progress in our research and development programs;

the magnitude and scope of our research and development programs and our abilityto establish, enforce and maintain strategic arrangements for research,development, clinical testing, manufacturing and marketing;

our progress with pre-clinical development and clinical trials;

the extent to which third party interest in Company's research and commercialproducts can be realized through effective partnerships;

the time and costs involved in obtaining regulatory approvals;

the costs involved in preparing, filing, prosecuting, maintaining, defending andenforcing patent claims;

the number and type of product candidates that we pursue; and

the development of major public health concerns, including the novel coronavirusoutbreak or other pandemics arising globally, and the current and future impactof it and COVID-19 on our business operations and funding requirements.

Our failure to raise capital or enter into applicable arrangements when neededwould have a negative impact on our financial condition. Additional debtfinancing may be expensive and require us to pledge all or a substantial portionof its assets. Further, if additional funds are obtained through arrangementswith collaborative partners, these arrangements may require us to relinquishrights to some of its technologies, product candidates or products that we wouldotherwise seek to develop and commercialize on its own. If sufficient capital isnot available, we may be required to delay, reduce the scope of or eliminate oneor more of its product initiatives.

We currently have no revenue generated from our principal operations intherapeutic and clinical product development through research and developmentefforts. There can be no assurance that we will be successful in maintaining ournormal operating cash flow and obtaining additional funds and that the timing ofour capital raising or future financing will result in cash flow sufficient tosustain our operations at least through one year after the issuance date.

Based on the factors above, there is substantial doubt about our ability tocontinue as a going concern. The consolidated financial statements were preparedassuming that we will continue to operate as a going concern. The consolidatedfinancial statements do not include any adjustments to reflect the possiblefuture effects on the recoverability and classification of assets or the amountsand classification of liabilities that may result from the outcome of thisuncertainty. Management's plans in regard to these matters are focused onmanaging our cash flow, the proper timing of our capital expenditures, andraising additional capital or financing in the future.

Critical Accounting Estimates

Our discussion and analysis of our financial condition and results of operationsis based upon our consolidated financial statements, which have been prepared inaccordance with accounting principles generally accepted in the United States.The preparation of these financial statements requires us to make estimates andassumptions that affect the reported amounts of assets, liabilities, revenues,expenses and related disclosures. On an on-going basis, we evaluate ourestimates and assumptions and we base our estimates on historical experience andon various other assumptions that are believed to be reasonable under thecircumstances, the results of which form the basis for making judgments aboutthe carrying values of assets and liabilities that are not readily apparent fromother sources. Actual results may differ from these estimates under differentassumptions and conditions.

Our significant accounting policies are more fully described in Note 1 to ourconsolidated financial statements included elsewhere in this Annual Report onForm 10-K. Our most critical accounting estimates include current andnon-current inventory, intangible assets, and stock-based compensation. Wereview our estimates and assumptions periodically and reflect the effects ofrevisions in the period in which they are deemed to be necessary. We believethat the following accounting policies are critical to the judgments andestimates used in preparation of our consolidated financial statements.

Allowance for Excess and Obsolete Inventory

Our inventory, particularly within our biomedical market, consists of certainproducts that have a long or, when frozen, indefinite shelf life. In addition,future demand for our products is uncertain. Accordingly, at each reportingperiod, we estimate a reserve for allowance for excess and obsolete inventory.This estimate is computed using historical sales data and inventory turnoverrates, which are subjective in nature and fluctuate between periods. Theestablishment of a reserve for excess and obsolete inventory establishes a newcost basis in the inventory with a corresponding adjustment to cost of sales. Ifwe are able to sell such inventory, any related reserves

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Originally posted here:
INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com

Artificial Wombs Will Change Abortion Rights Forever – WIRED

One day, human wombs may no longer be necessary for bearing children. In 2016, a research team in Cambridge, England, grew human embryos in ectogenesisthe process of human or animal gestation in an artificial environmentfor up to 13 days after fertilization. A further breakthrough came the next year, when researchers at the Childrens Hospital of Philadelphia announced that they had developed a basic artificial uterus named the Biobag. The Biobag sustained lamb fetuses, equivalent in size and development to a human fetus at roughly 22 weeks gestation, to full term successfully. Then, in August of 2022, researchers at the Weizmann Institute of Science in Israel created the worlds first synthetic embryos from mice stem cells. In the same month, scientists at the University of Cambridge used stem cells to create a synthetic embryo with a brain and a beating heart.

Ectogenesis has the potential to transform reproductive labor and reduce risks associated with reproduction. It could enable people with wombs to reproduce as easily as cisgender men do: without risks to their physical health, their economic safety, or their bodily autonomy. By removing natural gestation from the process of having children, ectogenesis could offer an equal starting point for people of all sexes and genders, particularly for queer people who wish to have children without having to rely on the morally ambiguous option of surrogacy.

If safe and effective ectogenesis were made accessibleas opposed to being privatized, which risks further entrenching social and economic inequalitiesthe technology could result in a more prosperous and more equal society. Yet development of ectogenesis could also wreak havoc on the hard-fought right of women and people with wombs to access safe and legal abortion, and could significantly weaken abortion policies worldwide.

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Current philosophical literature and legislation on abortion revolve around three debates: the moral status of the fetus, womens bodily autonomy, and the fetuss viability. Ectogenesis means that fetuses at all stages will be viable, so the technologys development will impact all three of these debates.

Antiabortion advocates tend to argue that the fetus is human at conception and that killing an innocent person by abortion is immoral. Pro-choice defendants of abortion rights, meanwhile, emphasize bodily autonomy and draw on arguments such as those made by philosopher Judith Thomson in her highly influential 1971 essayA Defense of Abortion.Thomson argues that even if a fetus is a person at the moment of conception, a womans bodily autonomyher right to decide what can happen in and to her bodymeans that it is morally acceptableto remove the fetus from her body. The ensuing death of the fetus is an inevitable consequence of ending the pregnancy, rather than the womans intention. This means that abortion is more an act of self-defense on the womans part than an intentional killing.

Meanwhile, in an effort to strike a balance between womens bodily autonomy and the fetuss moral status, abortion legislation in many countries uses fetal viabilitya fetuss ability to survive outside the womb, including when assisted by medical devicesas a measure to determine the moral acceptability of abortion. Under law in many places where abortion is permitted, the fetuss right to life transcends a womans bodily autonomy at the point when the fetus becomes viable. Abortion law in the United Kingdom, for example, allows abortion only before 24 weeks of fetal development, the earliest development stage from which a fetus can survive with the help of medical devices.

Successful ectogenesis would render the fetus viable at a very early stage, possibly even from conception.If ectogenesiseven partial ectogenesisbecomes available, it would then be possible for an unwanted fetus to be transferred into an artificial womb to continue developing without harming a womans bodily autonomy, depending on how the fetus is removed. In this way, women would be able to end their pregnancy without resorting to traditional abortion. Given this option, if a woman chooses traditional abortion regardless, the abortion will appear more like an intentional killing.

As a result, if abortion jurisprudence continues using fetal viability as its central criterion for whether abortion should be allowed, abortion in the ectogenesis era risks becoming less morally and socially acceptable than it is today.

There is a real risk that future legislation, especially in conservative communities, states, and countries, will fully prohibit abortion once ectogenesis becomes available. Though ectogenesis would make it possible to avoid pregnancy without ending the fetuss life, such an outcome is not necessarily a positive from a feminist point of view. The reality is that some women who choose abortion do so not only to end the pregnancypreserving bodily autonomybut also to avoid becoming a biological mother. Ectogenesis would still make hera biological mother against her will, and using it as an alternative to traditional abortion could therefore violate her reproductive autonomy.

Another possible scenario is one in which a woman wants to abort, but her partner wishes her not to. In the absence of the bodily autonomy argument, the fetuss viability and supposed right to develop, combined with the partners wishes, could result in a situation that pressures women to transfer the fetus to an artificial womb.

As ectogenesis develops further, activists and legislators will need to address the question: At what point is it justifiable for a woman to choose traditional abortion when there is another option that guarantees both the ending of the pregnancy and the fetuss ongoing chance at life? At what point should the desires of women not to become biological mothers outweigh a fetuss purported right to existence?

In exploring this question, it is useful to consider why some women might resist becoming biological mothers, even if they wouldnt need to shoulder the burden of raising a child that could be adopted after being transferred and fully developed in an artificial uterus. Some hesitation would likely be caused by social attitudes and pressures related to biological parenthood. Even if a legal system has absolved a biological mother of legal obligations toward her biological child, she might still feel a sense of obligation toward the child or guilt toward herself, for not enshrining the self-sacrificing qualities often idealized and associated with motherhood. Living with these emotions could cause the biological mother psychological harm, and she might also be at risk of encountering related social stigma.

Granted, there still remains the question of whether the desire to avoid possible social stigma or psychological distress is enough to outweigh a fetuss purported right to life. We believe that this question is highly debatable, depending on both the extent of the social stigma and the developmental stage of the fetus. Still, if social pressures and stigma are enough that a woman who uses ectogenesis would suffer, the desire of such a woman not to become a mother deserves to be respected, especially in the early stages of a fetuss development.

Legislation surrounding ectogenesis will also have to take bodily autonomy into account by ensuring that women have the right to decide which surgeries they allow to be performed on their bodies. Although it is unclear what form the procedure of transferring a fetus to an artificial uterus will take, it will almost certainly be invasive, likely similar to a cesarean section, at least for later-stage pregnancies. Women should have the right to reject ectogenetic surgery on the grounds of bodily autonomy; otherwise,as Canadian philosopher Christine Overall has pointed out, a forced transfer procedure would be akin to deliberately stealing human organs, which is deeply unethical.

Ectogenesis complicates abortion ethics, and forcing women to undergo ectogenetic surgery impinges on both their reproductive autonomy and their bodily freedom. Allowing early abortion in a world where ectogenesis exists could be a good compromise that reduces complications and ensures womens rights. However, for womens reproductive rights to be assured, abortion must remain an available option, even after ectogenesis becomes reality.

Future legislation will need to guarantee that ectogenesis is a choice rather than a new form of coercion. The right to abortion will need to be recentered in law around the value of reproductive autonomy and the right not to become a biological parent against ones will, as opposed to fetus viability. As this legal debate gains the attention of politicians, legislators, community leaders, and the wider public, how much people and societies respect womens right to choose will become more apparent than ever.

Read more:
Artificial Wombs Will Change Abortion Rights Forever - WIRED

Current Trends of iPSC Manufacturing and Clinical Applications – An … – geneonline

Expanding on previous feature articles and conference highlights, GeneOnline is honored to have Dr. Xianmin Zeng, the Founder and CEO of RxCell, a Bay Area-based biotechnology company, and Visiting Professor at the National University of Singapore Yong Loo Lin School of Medicine and, for an interview as part of the latest article on the Cell and Gene Therapy Special Series. During the interview, she covered important issues such as the latest trends in the induced pluripotent stem cells (iPSC) industry, the development of iPSC technology, and the clinical benefits of iPSC therapy.

Dr. Zeng began by describing her journey into the field of stem cell research. After receiving her Ph.D. from the Technical University of Denmark in 2000, she moved to the U.S. and joined the National Institutes of Health (NIH) as a postdoctoral researcher, working in the field of neuroscience and using the then-emerging embryonic stem cell technology to create dopaminergic neurons that could be used to develop potential cell replacement therapy in Parkinson's disease. In 2005, she moved to California to join the Buck Institute for Age Research, where she set up a stem cell research program. Following the advent of iPSC technology in 2006, her team started using iPSC as a cell source for developing new therapies, as well as for disease modeling and drug screening.

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Current Trends of iPSC Manufacturing and Clinical Applications - An ... - geneonline