Angelman Foundation Honors 4 for Their Research, Advocacy Efforts – Angelman Syndrome News

The Angelman Syndrome Foundation (ASF) recently honored four individuals for their exceptional contributions to the Angelman syndrome community and to advancing research.

Awards were presented to a special education specialist, researcher, former executive director of the foundation, and geneticist, during the 2019 ASF Scientific Symposium and Family Conference, an event that brought together families, educators, care providers, physicians, scientists, and other stakeholders to learn and discuss the latest on Angelman syndrome (AS).

Erin Sheldon was given the Harry & Audrey Angelman Award for Meritorious Service, an honor bestowed to those who demonstrate a strong commitment to enhancing disease awareness and understanding in their respective community, the ASF announced.

The mother of a daughter with Angelman, Sheldon has long supported AS families, advocating for inclusive schools and communities. Angelman is a complex neurological disorder that causes intellectual disabilities and issues with speech, among other symptoms. For her masters degree in education, Sheldon focused on the learning needs of students with complex disabilities.

The Dr. Claudia Benton Award for Scientific Research was presented to Stormy Chamberlain, PhD, a widely published researcher in AS and UBE3A, the protein coding gene associated with Angelman. She is an ASF board member who has made many presentations on the topic.

Chamberlain established a lab at the University of Connecticut, where shes an assistant professor in the genetics and developmental biology department, and assistant director of the graduate program in genetics and developmental biology. In her research, sheused induced pluripotent stem cells (IPSCs) to model and study genetic imprinting implicated in Angelman and other disorders.

Of note, IPSCs are derived from either skin or blood cells that have been reprogrammed back into a stem cell-like state, which allows for the development of an unlimited source of any type of human cell thats needed for therapeutic purposes. Genetic imprinting is a phenomenon that occurs when only one of the two copies of a given gene (one copy is inherited from each parent) is turned on, depending on the parent it originated from.

Receiving the ASFs Lifetime Achievement Award was Eileen Braun, who had been the foundations executive director from 2004 until this past spring. This award has now been renamed in her honor. The graduate of the Mayo Clinic School of Health Sciences, Braun has worked as a registered respiratory therapist at several medical centers, including the Mayo Clinic. She has four children, one of whom has Angelman, and currently serves as the ASFs director of operations.

During her time as ASF executive director, Braun started the ASF Walk fundraiser and organized the foundations first research roadmap (a plan that prioritized research investment toward improved patient care), and boosted research investment from $275,000 to more than $10 million. Braun also oversaw development of 12 international AS clinics and the worlds largest AS registry, and hosted 19 conferences and symposiums.

The first Eileen Braun Lifetime Achievement Award was given to Arthur Beaudet, MD, for his decades-long contribution to the fields of mammalian genetics and Angelman. A Yale University graduate and chair of molecular and human genetics at the Baylor College of Medicine, Beaudet and other scientists in 1997 identified the Angelman gene UBE3A. In 2015, his lab collaboratively showed that oligonucleotides could be used to activate the paternal copy of Angelman in mice, a promising step toward AS treatment.

A former National Institutes of Health research associate, Beaudet is a prolific author who served as president of the American Society of Human Genetics, and was elected to the National Academy of Medicine and National Academy of Sciences.

The board and staff of the Angelman Syndrome Foundation, as well as the entire community of families, teachers and scientists are grateful to these four individuals for their dedication and hard work, the organization said.

The ASF works to advance the awareness and treatment of AS through education, research, and patient and family support. Angelman syndrome occurs in about 1 in 15,000 live births.

Mary M. Chapman began her professional career at United Press International, running both print and broadcast desks. She then became a Michigan correspondent for what is now Bloomberg BNA, where she mainly covered the automotive industry plus legal, tax and regulatory issues. A member of the Automotive Press Association and one of a relatively small number of women on the car beat, Chapman has discussed the automotive industry multiple times of National Public Radio, and in 2014 was selected as an honorary judge at the prestigious Cobble Beach Concours dElegance. She has written for numerous national outlets including Time, People, Al-Jazeera America, Fortune, Daily Beast, MSN.com, Newsweek, The Detroit News and Detroit Free Press. The winner of the Society of Professional Journalists award for outstanding reporting, Chapman has had dozens of articles in The New York Times, including two on the coveted front page. She has completed a manuscript about centenarian car enthusiast Margaret Dunning, titled Belle of the Concours.

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Angelman Foundation Honors 4 for Their Research, Advocacy Efforts - Angelman Syndrome News

Fate Therapeutics raises $173 million in offering – The San Diego Union-Tribune

San Diegos Fate Therapeutics has raised $173 million in gross proceeds in a stock offering, the developer of immune cell therapies for cancer said Wednesday.

Fate sold 9.89 million shares at $17.50 each, including 1.29 million to underwriters under an option to buy more shares.

Net proceeds will be used to fund clinical trials and nonclinical studies, clinical manufacturing and other research and general corporate purposes.

Shares of Fate closed Wednesday at $17.61, up 62 cents for the day.

Fate is clinically testing a variety of immune cell therapies for cancer, using cells derived from donors and from artificially created stem cells called induced pluripotent stem cells. These forms of natural killer cells are being tested in solid tumors, ovarian and blood cancers.

On Sept. 3, Fate said the FDA had cleared an application to begin testing its most complicated immune cell therapy yet. Called FT596, it consists of natural killer cells genetically engineered to seek and destroy cells with certain tumor-associated proteins.

The genetic engineering technology has been used extensively in another type of immune cell called a T cell. These are equipped with what is known as Chimeric Antigen Receptors to create CAR T cells. These cells have produced a major advance in cancer therapy, rescuing patients close to death.

Natural killer cells seek abnormal cells with a more generalized mechanism. By equipping them with the CAR technology, Fate is trying to create more versatile cells with the properties of both.

Fate said it plans to test FT596 alone and in combination therapy for B-cell lymphoma and chronic lymphocytic leukemia.

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Fate Therapeutics raises $173 million in offering - The San Diego Union-Tribune

Induced Pluripotent Stem Cells Market is expected to reach US$ 2299.5 Mn by the end of the forecast period in 2026 – Zebvo

The healthcare industry has been focusing on excessive research and development in the last couple of decades to ensure that the need to address issues related to the availability of drugs and treatments for certain chronic diseases is effectively met. Healthcare researchers and scientists at the Li Ka Shing Faculty of Medicine of the Hong Kong University have successfully demonstrated the utilization of human induced pluripotent stem cells or hiPSCs from the skin cells of the patient for testing therapeutic drugs.

The success of this research suggests that scientists have crossed one more hurdle towards using stem cells in precision medicine for the treatment of patients suffering from sporadic hereditary diseases. iPSCs are the new generation approach towards the prevention and treatment of diseases that takes into account patients on an individual basis considering their genetic makeup, lifestyle, and environment. Along with the capacity to transform into different body cell types and same genetic composition of the donors, hiPSCs have surfaced as a promising cell source to screen and test drugs.

In the present research, hiPSC was synthesized from patients suffering from a rare form of hereditary cardiomyopathy owing to the mutations in Lamin A/C related cardiomyopathy in their distinct families. The affected individuals suffer from sudden death, stroke, and heart failure at a very young age. As on date, there is no exact treatment available for this condition. This team in Hong Kong tested a drug named PTC124 to suppress specific genetic mutations in other genetic diseases into the iPSC transformed heart muscle cells. While this technology is being considered as a breakthrough in clinical stem cell research, the team at Hong Kong University is collaborating with drug companies regarding its clinical application.

The unique properties of iPS cells provides extensive potential to several biopharmaceutical applications. iPSCs are also used in toxicology testing, high throughput, disease modeling, and target identification. This type of stem cell has the potential to transform drug discovery by offering physiologically relevant cells for tool discovery, compound identification, and target validation. A new report by Persistence Market Research (PMR) states that the globalinduced pluripotent stem or iPS cell marketis expected to witness a strong CAGR of 7.0% from 2018 to 2026. In 2017, the market was worth US$ 1,254.0 Mn and is expected to reach US$ 2,299.5 Mn by the end of the forecast period in 2026.

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Customization to be the Key Focus of Market Players

Due to the evolving needs of the research community, the demand for specialized cell lines have increased to a certain point where most vendors offering these products cannot depend solely on sales from catalog products. The quality of the products and lead time can determine the choices while requesting custom solutions at the same time. Companies usually focus on establishing a strong distribution network for enabling products to reach customers from the manufacturing units in a short time period.

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Entry of Multiple Small Players to be Witnessed in the Coming Years

Several leading players have their presence in the global market; however, many specialized products and services are provided by small and regional vendors. By targeting their marketing strategies towards research institutes and small biotechnology companies, these new players have swiftly established their presence in the market.

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Induced Pluripotent Stem Cells Market is expected to reach US$ 2299.5 Mn by the end of the forecast period in 2026 - Zebvo

induced pluripotent stem cells (iPSCs) market reached $2.1 billion in 2016 The market should reach $3.6 billion in 2021 – ScoopJunction

posted on September 18, 2019

The global market for induced pluripotent stem cells (iPSCs) reached $2.1 billion in 2016. The market should reach $3.6 billion in 2021, increasing at a compound annual growth rate (CAGR) of 11.6% from 2016 through 2021.

Report Scope:

This study is focused on the market side of iPSCs rather than its technical side. Different market segments for this emerging market are covered. For example, application-based market segments include academic research, drug development and toxicity testing, and regenerative medicine; product function-based market segments include molecular and cellular engineering, cellular reprogramming, cell culture, cell differentiation and cell analysis; iPSC-derived cell-type-based market segments include cardiomyocytes, hepatocytes, neurons, endothelia cells and other cell types; geography-based market segments include the U.S., Europe, Asia-Pacific and Rest of World. Research and market trends are also analyzed by studying the funding, patent publications and research publications in the field.

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Report Includes:

An overview of the global market for induced pluripotent stem cells. Analyses of global market trends with data from 2015 and 2016, and projections of compound annual growth rates (CAGRs) through 2021. Information on induced pluripotent stem cell research products, defined as all research tools including but not limited to: induced pluripotent stem cells and various differentiated cells derived from induced pluripotent stem cells; various related assays and kits, culture media and medium components, such as serum, growth factors and inhibitors, antibodies, enzymes, and many others that can be applied for the specific purpose of executing induced pluripotent stem cell research. Discussion of important manufacturers, technologies, and factors influencing market demand, such as the driving forces and limiting factors of induced pluripotent stem cell market growth. Profiles of major players in the industry.

Report Summary

Its been over 10 years since the discovery of induced pluripotent stem cell (iPSC) technology. The market has gradually become an important part of the life sciences industry during recent years. Particularly for the past five years, the global market for iPSCs has experienced a rapid growth. The market was estimated at $1.7 billion in 2015 and over $2 billion in 2016, with an average 18% growth. The overall iPSC market is forecast to continue its relatively rapid growth and reach over $3.6 billion in 2021, with an estimated compound annual growth rate (CAGR) of 11.6% from 2016 through 2021.

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Key Drivers for Market Growth

This report has identified several key drivers for the rapidly growing market: iPSC shold promising hope for therapeutic solutions for diseases without ethical issues. A series of technical breakthroughs were made in recent years for improving cellular reprogramming, differentiation and large-scale production of GMP- grade iPSCs derived cells toward clinical usability. The pharmaceutical industry needs better cell sources such as iPSC-derived functional cells for drug toxicity testing and drug screening. The U.S. government has been encouraging the marketing of stem cells, including iPSCs. The U.S. Food and Drug Administration (FDA) has been authorized to provide orphan drug designations for many of the therapies developed for rare diseases such as Parkinsons and Huntingtons using stem cells. The provisions of grants from organizations, such as the National Institutes of Health (NIH) and the California Institute for Regenerative Medicine (CIRM) have been encouraging for the research institutes to venture into iPSC research. Rapidly growing medical tourism and contract research outsourcing drives the Asia-Pacific stem cell market. Cellular reprogramming, including iPSC technology, was awarded the 2012 Nobel Prize. The first human iPSC clinical trial started in August 2014, and the recent report of the first macular degeneration patient treated with the sheets of retinal pigmented epithelial cells made from iPSCs was encouraging. iPSC technology is developing into a platform for precision and personalized medicine, which is experiencing rapid growth globally. New biotechnologies such as genome editing technology are advancing iPSCs into more and better uses.

This report identifies key revenue segments for the iPSC market from various aspects. The applicationbased segments include the research, drug development and clinical markets; the product functionbased segments include molecular and cellular engineering, cellular reprogramming, cell culture, cell differentiation and cell analysis. The current major revenue segment is the drug development and toxicity testing sector, but the market for regenerative medicine is the fastest growing one. The marketfor clinical applications is not fully established, but the market for the translational medicine research of iPSC is also growing very quickly.

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induced pluripotent stem cells (iPSCs) market reached $2.1 billion in 2016 The market should reach $3.6 billion in 2021 - ScoopJunction

Common Prostate Drug May Slow Progression of Parkinson, Researchers Say – AJMC.com Managed Markets Network

Terazosin, a drug used to treat enlarged prostate, may also be able to slow the progression of Parkinson disease.

The finding is the result of a collaboration involving researchers in China and at the University of Iowa (UI), combining observations from animal experiments with information from clinical databases regarding men taking the drug.

Lei Liu, PhD, at Capital Medical University in Beijing, China, found that terazosin could block cell death. Using toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, the drug increased brain adenosine triphosphate levels and slowed or prevented neuron loss if it was given before the onset of cell death. In addition, the drug could slow or stop neurodegeneration, even if treatment was delayed until after neurodegeneration had started to develop. Liu's team discovered that the cell-protective activity was due to terazosin's ability to activate phosphoglycerate kinase 1 (PGK1), an enzyme critical for cellular energy production.

Researchers then probed databases looking at patients who took terazosin and found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses.

This suggests that in patients taking terazosin and related drugs, enhanced PGK1 activity and increased glycolysis may slow neurodegeneration in PD.

"When we tested the drug in various different animal models of PD, they all got better. Both the molecular changes in the brain associated with cell death and the motor coordination in the animals improved," said Liu, a professor in the Beijing Institute for Brain Disorders, in a statement.

Nandakumar Narayanan, MD, PhD, a UI neurologist, and Jordan Schultz, PharmD, UI assistant professor of psychiatry, examined the Parkinson's Progression Markers Initiative database, which is sponsored by The Michael J. Fox Foundation for Parkinson's Research. The data showed that men with PD who were taking terazosin had reduced rates of progressive motor disability compared to men with PD who were taking a different drug, tamsulosin, for enlarged prostate.

While tamsulosin is also used to treat benign prostatic hyperplasia, unlike terazosin, it does not have any effect on the PGK1 enzyme, making ita good control.

Only 13 men were identified who were taking terazosin or 1 of 2 similar drugs that also activate the PGK1 enzyme, compared with 293 men with PD who were either taking tamsulosin or were not taking any of these drugs. While the differences in motor decline between the 2 groups were statistically significant, the team looked to confirm the findings using the larger IBM Watson/Truven Health Analytics MarketScan Database, which includes de-identified records of more than 250 million people.

From there, researchers identified 2880 Parkinson's patients taking 1 of the 3 drugs that target PGK1 (terazosin, doxazosin, or alfusin) and a comparison group of 15,409 PD patients taking tamsulosin. Using medical codes to track PD-related diagnoses and hospital or clinic visits for all the patients, the data suggested that under real world conditions, terazosin and related drugs reduce the signs, symptoms, and complications of PD. Relative to patients with PD taking tamsulosin, those on terazosin or the 2 other drugs had reduced clinic and hospital visits for motor symptoms (relative risk [RR] 0.77; 95% CI, 0.700.84), nonmotor symptoms (RR 0.78; 95% CI, 0.730.83), and PD complications (RR 0.76; 95% CI, 0.710.82).

Patients using terazosin also had a reduced risk of a PD diagnosis, the researchers said.

Reference

Cai R, Zhang Y, Simmering JE, et al. Enhancing glycolysis attenuates Parkinsons disease progression in models and clinical databases [published online September 16, 2019].J Clin Invest. doi: 10.1172/JCI129987.

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Common Prostate Drug May Slow Progression of Parkinson, Researchers Say - AJMC.com Managed Markets Network

Stem Cell-Derived Cells Market to Record an Exponential CAGR by 2025 – NewsVarsity

Stem cell-derived cells are ready-made human induced pluripotent stem cells (iPS) and iPS-derived cell lines that are extracted ethically and have been characterized as per highest industry standards. Stem cell-derived cells iPS cells are derived from the skin fibroblasts from variety of healthy human donors of varying age and gender. These stem cell-derived cells are then commercialized for use with the consent obtained from cell donors. These stem cell-derived cells are then developed using a complete culture system that is an easy-to-use system used for defined iPS-derived cell expansion. Majority of the key players in stem cell-derived cells market are focused on generating high-end quality cardiomyocytes as well as hepatocytes that enables end use facilities to easily obtain ready-made iPSC-derived cells. As the stem cell-derived cells market registers a robust growth due to rapid adoption in stem cellderived cells therapy products, there is a relative need for regulatory guidelines that need to be maintained to assist designing of scientifically comprehensive preclinical studies. The stem cell-derived cells obtained from human induced pluripotent stem cells (iPS) are initially dissociated into a single-cell suspension and later frozen in vials. The commercially available stem cell-derived cell kits contain a vial of stem cell-derived cells, a bottle of thawing base and culture base.

The increasing approval for new stem cell-derived cells by the FDA across the globe is projected to propel stem cell-derived cells market revenue growth over the forecast years. With low entry barriers, a rise in number of companies has been registered that specializes in offering high end quality human tissue for research purpose to obtain human induced pluripotent stem cells (iPS) derived cells. The increase in product commercialization activities for stem cell-derived cells by leading manufacturers such as Takara Bio Inc. With the increasing rise in development of stem cell based therapies, the number of stem cell-derived cells under development or due for FDA approval is anticipated to increase, thereby estimating to be the most prominent factor driving the growth of stem cell-derived cells market. However, high costs associated with the development of stem cell-derived cells using complete culture systems is restraining the revenue growth in stem cell-derived cells market.

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The global Stem cell-derived cells market is segmented on basis of product type, material type, application type, end user and geographic region:

Segmentation by Product Type Stem Cell-Derived Cell Kits Stem Cell-Derived Definitive Endoderm Cell Kits Stem Cell-Derived Beta Cell Kits Stem Cell-Derived Hepatocytes Kits Stem Cell-Derived Cardiomyocytes Kits Accessories

Segmentation by End User Hospitals Research and Academic Institutions Biotechnology and Pharmaceutical Companies Contract Research Organizations/ Contract Manufacturing Organizations

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The stem cell-derived cells market is categorized based on product type and end user. Based on product type, the stem cell-derived cells are classified into two major types stem cell-derived cell kits and accessories. Among these stem cell-derived cell kits, stem cell-derived hepatocytes kits are the most preferred stem cell-derived cells product type. On the basis of product type, stem cell-derived cardiomyocytes kits segment is projected to expand its growth at a significant CAGR over the forecast years on the account of more demand from the end use segments. However, the stem cell-derived definitive endoderm cell kits segment is projected to remain the second most lucrative revenue share segment in stem cell-derived cells market. Biotechnology and pharmaceutical companies followed by research and academic institutions is expected to register substantial revenue growth rate during the forecast period.

North America and Europe cumulatively are projected to remain most lucrative regions and register significant market revenue share in global stem cell-derived cells market due to the increased patient pool in the regions with increasing adoption for stem cell based therapies. The launch of new stem cell-derived cells kits and accessories on FDA approval for the U.S. market allows North America to capture significant revenue share in stem cell-derived cells market. Asian countries due to strong funding in research and development are entirely focused on production of stem cell-derived cells thereby aiding South Asian and East Asian countries to grow at a robust CAGR over the forecast period.

Some of the major key manufacturers involved in global stem cell-derived cells market are Takara Bio Inc., Viacyte, Inc. and others.

The report covers exhaustive analysis on: Stem cell-derived cells Market Segments Stem cell-derived cells Market Dynamics Historical Actual Market Size, 2014 2018 Stem cell-derived cells Market Size & Forecast 2019 to 2029 Stem cell-derived cells Market Current Trends/Issues/Challenges Competition & Companies involved Stem cell-derived cells Market Drivers and Restraints

Regional analysis includes North America Latin America Europe East Asia South Asia Oceania The Middle East & Africa

Report Highlights: Shifting Industry dynamics In-depth market segmentation Historical, current and projected industry size Recent industry trends Key Competition landscape Strategies of key players and product offerings Potential and niche segments/regions exhibiting promising growth A neutral perspective towards market performance

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Stem Cell-Derived Cells Market to Record an Exponential CAGR by 2025 - NewsVarsity

Automated Large-Scale Production of Retinal Organoids – Advanced Science News

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The retina is the innermost layer in the eye and is responsible for converting light energy to electrical signals which are transmitted to the brain and are processed into an image. It consists of six major cell types which are organized in a specific laminated manner to allow it to function properly.

Non-treatable visual impairment caused by the degeneration of the retina is increasingly affecting millions of people worldwide. However, there are currently no adequate in vivo or in vitro models that would allow the study of human retinal development and pathological processes in a disease state. Additionally, most of drug screening is currently performed on model animals that do not recapitulate human physiology and retinal function.

The advent of human induced pluripotent stem cells and an increased understanding of human retinal development has allowed scientists to develop a method for generating retinal organoids, which are miniature synthetic counterparts to human retina.

In a recent study published in Current Protocols in Stem Cell Biology, Professor Majlinda Lako and co-workers describe a method for large-scale production of retinal organoids that contain all major retinal cell types.

The study offers an organoid-based system, which is relevant to human physiology and has a wide range of applications, including drug testing, disease modelling, cell therapy, and in the study of human retina development.

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Automated Large-Scale Production of Retinal Organoids - Advanced Science News

How a Centuries-Old Sculpting Method Is Helping 3D Print Organs With Blood Vessels – Singularity Hub

Blood vessels are the lifeline of any organ.

The dense web of channels, spread across tissues like a spider web, allow oxygen and nutrients to reach the deepest cores of our hearts, brains, and lungs. Without a viable blood supply, tissues rot from the inside. For any attempt at 3D printing viable organs, scientists have to tackle the problem of embedding millions of delicate blood vessels throughout their creation.

Its a hideously hard problem. Although blood vessels generally resemble tree-like branches, their distribution, quantity, size, and specific structure vastly differs between people. So far, the easiest approach is to wash out cells from donated organs and repopulate the structure with recipient cellsa method that lowers immunorejection after transplant. Unfortunately, this approach still requires donor organs, and with 20 people in the US dying every day waiting for an organ transplant, its not a great solution.

This week, a team from Harvard University took a stab at the impossible. Rather than printing an entire organ, they took a Lego-block-like approach, making organ building blocks (OBBs) with remarkably high density of patient cells, and assembled the blocks into a living environment. From there, they injected a sacrificial ink into the proto-tissue. Similar to pottery clay, the ink hardens upon curingleaving a dense, interconnected 3D network of channels for blood to run through.

As a proof of concept, the team printed heart tissue using the strategy. Once the block fused, the lab-made chunk of heart could beat in synchrony and remained healthy for at least a week.

The technology, SWIFT (an eyebrow-raising backcronym of sacrificial writing into functional tissue), is a creative push into a new generation of 3D biofabrication. Although OBBs have been around, the team explained, little attention was previously paid to putting the Lego pieces together with blood vessels.

This is an entirely new paradigm for tissue fabrication, said study author Dr. Mark Skylar-Scott. The focus is on vessels, which will support 3D printed living tissue that may eventually be used to repair damaged parts of a natural body, or even replace entire human organs with lab-grown versions, he added.

[Its] beautiful work, commented tissue engineer Dr. Jordan Miller at Rice University, who was not involved in the study.

SWIFT straddles two wildly diverse fields across centuries: organoids and 15th-century lost-wax sculpturing.

Youve heard of organoids. Often dubbed mini-organs, these lentil-sized blobs of tissue remarkably mimic particular aspects of entire organsbrain organoids, for example, show the characteristic nerve cell types of firings of a preemie baby. The cellular inhabitants that make up organoids are what especially caught the teams attention: most are grown from induced pluripotent stem cells (iPSCs), which are often skin cells de-aged in a way that they can develop into almost any cell type with a little chemical prodding.

Because organoids are built from a patients own cells, theyre completely compatible with the host for an immune standpoint. That particular strength caught the teams attention: organoids, they reasoned, make the ideal OBBor Lego piecesto biomanufacture patient- and organ-specific tissues with all the desired properties.

For example, the team explained, organoids are packed with a high density of cells, which is usually hard to achieve with traditional 3D tissue printing. Under the right conditions, they also develop similarly to real organs in terms of cellular composition and microarchitecture to support functionfor about a year. Without a blood vessel network, all organoids die.

Heres where lost-wax technique comes in.

First, a very brief explainer. Throughout the Renaissance, the majority of Italian sculptors used the technique to fabricate bronze statues. In the simplest method, a statuette is first modeled in beeswax and covered in potters clay. Once dried, the assembly is heatedthe clay is fired into ceramics, and the wax melts and flows away (hence, lost). Once cooled, the entire project is now a hollow ceramic mold, through which the artist can pour in molten metal.

Now, replace beeswax with sacrificial bio-ink, and thats pretty much how SWIFT carves out its intricate tunnels of blood vessels.

The entire fabrication process is two main steps. The team first grew hundreds of thousands of proto-organoids inside culture dishes. These tiny blobs are so small they dont yet need to be churned inside a bioreactor, but theyre mightily packed with roughly 200 million cells every milliliterabout the bottom bit of a teaspoon. These make up the techniques building blocks, or OBBs.

Next, roughly 400,000 OBBs are mixed with a dense, gel-like liquid with the consistency of mayonnaise at a low temperature. The liquid is filled with collagen, a protein that keeps our skin elastic, and other synthetic versions. The OBBs are now somewhat suspended inside the gel-like matrix, which is ideally suited for creating vascular channels, the team said. Altogether, the organoids and gel are compacted into a density similar to human tissue, making up the raw material for further sculpting.

Now the fun second step. Using a 3D printer, the team moved a tiny nozzle containing both harmless red ink and gelatin into the mixture, depositing both in a pre-programmed manner. In this way, the team was able to draw intricate branch-like patterns into the organoid-gel mixture. Similar to squeezing frosting out of a bag, the team was able to adjust the diameter of the gelatin ink by nearly two-fold, mimicking the usual structure of blood vesselsthick main channels that increasingly become tinier.

Once the network was fully printed, they then gently heated the mixture to body temperature. The matrix stiffens, and the gelatin inkacting like Jello left under the sun for too longmelts and is washed away. What remains is a network of OBBS, or organoids, linked with a vascular structure that can now be filled with blood.

As a proof of concept, the team went straight for the heartcardiac tissue, that is. They repeated the steps using heart-derived cells, and kept the resulting chunk of heart, a little bigger than half an inch inside a chamber, filled with a nutritious, oxygen-rich bath.

Within a week, individual organoids embedded inside the gel fused together into a collective: the tissue was able to contract almost 50 percent better than immediately after printing, and the beating rhythm synchronized, suggesting that the lab-grown tissue had further matured.

The tissue even reacted similarly to a normal heart. When the team infused a drug that increases heart rate into those printed vessels, the tissue doubled in its heartbeat. Similarly, drugs that normally decrease heart muscle contraction also worked on the mini-heart. As a final proof of concept demo, the team printed a chunk of heart tissue with a branch of the coronary arterya main blood vessel branch that normally wraps the heart.

The new study is hardly the first try at printing organs with blood vessels. Miller, for example, biomanufactured a hydrogel that mimicked a lung air sac earlier this May. Layer by layer, the precise anatomy of the lung-mimicking structure is constructed with liquid hydrogel, and solidified using light.

The new study stands out in its sheer creativity. By combining organoids with an ancient sculpture technique, the team was able to pack far more cells into the resulting structure, while tapping into the natural mini-organization that stems from organoids. The results arent just promising for printing larger, more intricate human organs with a blood supplythey could also help inform organoid research, which has struggled to keep the pseudo-organs alive.

The team is planning to transplant their SWIFT tissue into animals to further examine their function and health. But to the team, the main goal is to finally bring 3D-printed organs to people desperately on the transplant waiting list.

Our method opens new avenues for creating personalized organ-specific tissues with embedded vascular channels for therapeutic applications, they said.

Image Credit: Wyss Institute at Harvard University / CC BY-NC-ND 4.0

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How a Centuries-Old Sculpting Method Is Helping 3D Print Organs With Blood Vessels - Singularity Hub

BIOLIFE4D Successfully 3D Bioprints a Miniature Human HeartOne Step Closer to Bioprinting Transplantable Organs – BioSpace

Bioprinting is a type of 3D printing to manufacture biological. So far, the process has been used to develop organs or organoidssmaller versions of organs that are at least partially functionaland can be used as models for research. Ultimately researchers hope they can bioprint organs that can be used for transplants.

Chicago-based BIOLIFE4D recently bioprinted a 3D miniature human heart, which they say is a big step toward producing a full-sized human heart that could be used for transplant. The company has research facilities at JLABS in Houston.

The miniature heart had all the structures of a full-sized heart, with four internal chambers. The company says it is as close as anyone has gotten to a fully functioning heart via 3D bioprinting.

We are extremely proud of what we have accomplished, from the ability to 3D bioprint human cardiac tissue last summer to a mini heart with full structure now, said Ravi Birla, the companys chief science officer. These milestones are a testament to the hard work of our team and the proprietary process we have developed that enables this type of scientific achievement. We believe we are at the forefront of whole heart bioengineering, a field that has matured quickly over the last year, and well positioned to continue our rapid scientific advancement. Today is an exciting day, but we continue forward earnestly toward the end goal of 3D bioprinting whole human hearts.

3D printing is sometimes called additive manufacturing. It is a way of making three-dimensional solid objects from a digital file. In many ways, the only limitations are the limits on the complexity of the design. 3D printing used in industrial applications typically use carbon fiber as a source material. But bioprinting uses a variety of biological materials, such as single cell suspensions, as the source materials.

In the case of BIOLIFE4Ds heart, they developed a proprietary bioink with a unique composition of different extracellular matrix compounds. These compounds are very similar to the properties of a mammalian heart. The company also developed a novel bioprinting algorithm made up of printing parameters optimized for the whole heart, which it coupled with patient-derived cardiomyocytes. Although the heart is small in size, it has many of the features of a human heart.

BIOLIFE4D isnt the only company working in this specific area. In April, researchers at Tel Aviv University successfully printed the first 3D human heart. The research team used the patients own cells and various biological materials such as collagen and glycoprotein. Their work was published in the journal Advanced Science.

This heart is made from human cells and patient-specific biological materials, stated Tal Dvir, lead researcher. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models. People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future.

Dvir and his team began by taking biopsies of fatty tissues from the omentum, a fold of visceral peritoneum that hangs from the stomach, in the abdomen of humans and pigs. They then separated the cellular materials from extraneous materials and reprogrammed the cellular materials to become pluripotent stem cells. From these, they were able to develop all three body layers that had the potential to produce any cell or tissue in the body.

They then built an extracellular matrix from collagen and glycoproteins into a hydrogel using the bioprinter. They mixed the cells with the hydrogel, which were then differentiated into cardiac or endothelial cells. This created what theyre calling patient-specific, immune-compatible cardiac patches complete with blood vessels.

From that point, they then created an entirebut smallbioengineered and bioprinted human heart.

Last year, Poietis, a Pessac, France-based company, along with Prometheus, a division of Skeletal Tissue Engineering at Leuven, Belgium, announced they had entered into a two-year Collaborative Research Agreement to develop high-precision 3D Bioprinting of tissue engineered Advanced Therapeutic Medicinal Products (ATMPs) for skeletal regeneration.

Prometheus focuses on tissue-engineered ATMPs with a focus on skeletal regeneration. Poietis is interested in using 3D bioprinting of single cell suspensions into large, patterned tissue structures, especially the laser-assisted bioprinting of multicellular micro-aggregates embedded in bioinks for the formation of layered cellular structures.

What this comes down to is a collaboration to print bone that can be used in transplants or other orthopedic, musculoskeletal or spine-related applications.

Poietis already has a product on the market, Poieskin, a human full thickness skin model produced entirely by 3D bioprinting. It is made up of a dermal compartment composed of primary human fibroblasts embedded in a collagen I matrix overlaid by a stratified epidermis derived from primary human keratinocytes.

In May, researchers with Rice University developed a new approach resulting in exquisitely entangled vascular networks that mimic the bodys natural passageways for blood, air, lymph and other vital fluids. The research was published in the journal Science.

One of the biggest roadblocks to generating functional tissue replacements has been our inability to print the complex vasculature that can supply nutrients to densely populated tissues, stated Jordan Miller of Rice University. Further, our organs actually contain independent vascular networkslike the airways and blood vessels of the lung or the bile ducts and blood vessels in the liver. These interpenetrating networks are physically and biochemically entangled, and the architecture itself is intimately related to tissue function. Ours is the first bioprinting technology that addresses the challenge of multivascularization in a direct and comprehensive way.

Also in May, San Diego-based Organovo entered a collaboration agreement with Melissa Little at the Murdoch Childrens Research Institute (MCRI), The Royal Childrens Hospital, in Melbourne, Australia, and Ton Rabelink at Universiteit Leiden (LUMC), Leiden, Netherlands. The collaboration will focus on expanding the use of 3D bioprinted stem cell-based therapeutic tissues. The goal is to develop treatments for end-stage renal disease.

The collaboration will utilize Organovos bioprinting platform, MCRIs advanced stem cell differentiation technology, and LUMCs cell lines and clinical expertise. The partnership is funded by Stem Cells Australia and CSL Limited.

And in 2018, United Therapeutics and Lung Biotechnology made a collaboration pact with Israeli 3D bioprinting company CollPlant. United paid CollPlant $5 million up front with up to $15 million in milestones to supply bioink to Lung Biotechnology. CollPlants recombinant human collagen (rhCollagen) is grown from tobacco plants engineered with five human genes. The purified collagen can be used as a scaffold for 3D bioprinting solid organs.

BIOLIFE4D has had several breakthroughs in this area. Earlier this year it successfully 3D bioprinted individual heart components, and in June 2018 it successfully 3D bioprinted a cardiac patch out of human cardiac tissue.

The companys 3D bioprinting process gives the researchers the opportunity to reprogram a patients own white blood cells to induced pluripotent stem (iPS) cells, then to force the iPS cells to differentiate into different types of cardiac cells to be used as individual cardiac components and eventually, into a human heart that could be used for transplant.

This is an incredibly exciting time for BIOLIFE4D, and we are so proud of Dr. Birla and the team for this tremendous accomplishment, said Steven Morris, the companys chief executive officer. We began this journey with an end goal of developing a technology that has the potential to save lives, and we are a step closer to that today. We will continue our work until we are able to 3D bioprint full-sized hearts for viable transplant, and change the way heart disease is treated forever.

Read more:
BIOLIFE4D Successfully 3D Bioprints a Miniature Human HeartOne Step Closer to Bioprinting Transplantable Organs - BioSpace