Category Archives: Stell Cell Research


Scientists Grew ‘Mini Brains’ From Stem Cells. Then, The Brains Sort-of Developed Eyes. – ScienceAlert

Mini brains grown in a lab from stem cells spontaneously developed rudimentary eye structures, scientists reported in a fascinating paper in 2021.

On tiny, human-derived brain organoids grown in dishes, two bilaterally symmetrical optic cups were seen to grow, mirroring the development of eye structures in human embryos.

This incredible result will help us to better understand the process of eye differentiation and development, as well as eye diseases.

"Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell types similar to those found in the body," said neuroscientist Jay Gopalakrishnan of University Hospital Dusseldorf in Germany.

"These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies."

Brain organoids are not true brains, as you might be thinking of them. They are small, three-dimensional structures grown from induced pluripotent stem cells - cells harvested from adult humans and reverse engineered into stem cells, that have the potential to grow into many different types of tissue.

In this case, these stem cells are coaxed to grow into blobs of brain tissue, without anything resembling thoughts, emotions, or consciousness.

Such 'mini brains' are used for research purposes where using actual living brains would be impossible, or at the very least, ethically tricky - testing drug responses, for example, or observing cell development under certain adverse conditions.

This time, Gopalakrishnan and his colleagues were seeking to observe eye development.

In previous research, other scientists had used embryonic stem cells to grow optic cups, the structures that develop into almost the entire globe of the eye during embryonic development. And other research had developed optic cup-like structures from induced pluripotent stem cells.

Rather than grow these structures directly, Gopalakrishnan's team wanted to see if they could be grown as an integrated part of brain organoids. This would add the benefit of seeing how the two types of tissue can grow together, rather than just growing optic structures in isolation.

"Eye development is a complex process, and understanding it could allow underpinning the molecular basis of early retinal diseases," the researchers wrote in their paper.

"Thus, it is crucial to study optic vesicles that are the primordium of the eye whose proximal end is attached to the forebrain, essential for proper eye formation."

Previous work in the development of organoids showed evidence of retinal cells, but these did not develop optic structures, so the team changed their protocols. They didn't attempt to force the development of purely neural cells at the early stages of neural differentiation, and added retinol acetate to the culture medium as an aid to eye development.

Their carefully tended mini brains formed optic cups as early as 30 days into development, with the structures clearly visible at 50 days. This is consistent with the timing of eye development in the human embryo, which means these organoids could be useful for studying the intricacies of this process.

There are other implications, too. The optic cups contained different retinal cell types, which organized into neural networks that responded to light, and even contained lens and corneal tissue. Finally, the structures displayed retinal connectivity to regions of the brain tissue.

"In the mammalian brain, nerve fibers of retinal ganglion cells reach out to connect with their brain targets, an aspect that has never before been shown in an in vitro system," Gopalakrishnan said.

And it's reproducible. Of the 314 brain organoids the team grew, 73 percent developed optic cups. The team hopes to develop strategies for keeping these structures viable on longer time-scales for performing more in-depth research with huge potential, the researchers said.

"Optic vesicle-containing brain organoids displaying highly specialized neuronal cell types can be developed, paving the way to generate personalized organoids and retinal pigment epithelial sheets for transplantation," they wrote in their paper.

"We believe that [these] are next-generation organoids helping to model retinopathies that emerge from early neurodevelopmental disorders."

The research has been published in Cell Stem Cell.

A version of this article was first published in August 2021.

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Scientists Grew 'Mini Brains' From Stem Cells. Then, The Brains Sort-of Developed Eyes. - ScienceAlert

Mitophagy in human health, ageing and disease – Nature.com

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Mitophagy in human health, ageing and disease - Nature.com

From immunology to artificial intelligence: revolutionizing latent … – Military Medical Research

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From immunology to artificial intelligence: revolutionizing latent ... - Military Medical Research

Investing in healthcare where are the opportunities? – Hargreaves Lansdown

Key takeaways

The healthcare sector covers the huge range of activities needed to deliver medical care globally. Things like diagnostic tools and the wide selection of pharmaceuticals and medical devices used to treat patients.

Then there are research organisations and insurers. This universe also includes privately-run care facilities, as well as medical distributors and pharmacies.

Past performance isnt a guide to the future. Source: Refinitiv Eikon, 26 November 2023.

The pandemic has been hugely disruptive for the healthcare sector. It caused significant delays in clinical trials pipelines and an unprecedented backlog in patient care. Made even worse by difficulties in the supply chain.

So maybe its no surprise that the sector underperformed at the peak of the pandemic. But it also let certain players demonstrate excellence in science innovation. They led the world's response to the crisis through the development of new treatments, and most importantly the rollout of vaccines in record time.

In 2022 this let the sector keep generating positive returns, while the wider market retreated as the global economy saw high inflation and rising interest rates.

More recently though, those companies that saw a boost from tackling COVID-19, have struggled to replace the revenue from falling sales of these same products. That's seen a lot of the initial outperformance reverse in 2023.

One of the biggest stories coming from the healthcare industry is the boom in next-generation medicines for combating obesity and diabetes. These have the potential to become the biggest category of pharmaceuticals in medical history.

For now, this space is dominated by a handful of trailblazers, but theres a swarm of competitors waiting in the wings. This reflects the growing burden of chronic diseases. Tackling these conditions makes commercial sense and potentially creates long-term revenue streams.

We also see an opportunity in the evolution of new treatment mechanisms that can help or potentially cure serious diseases. Despite huge advances in the standard of care, cancer is still responsible for nearly one in six deaths worldwide and is by far still the busiest area for pharmaceutical research.

Immunotherapy, where the body's own immune system is honed to fight cancerous cells has been a key driver of improved survival rates. But there's room to improve its efficacy and increase the number of people and cancers it can be used on.

Gene therapy and stem cell treatments are other breakthroughs keeping the white coats busy, and they could also have use cases in other disease areas.

But it's not all about new products.

Pursuing approvals in new territories, patient populations, and conditions for medicines that already exist in the market makes perfect sense. This is a concept thats become known as a pipeline in a product.

Information and communication technology could also have a transformational effect on healthcare delivery.

The adoption of telemedicine was accelerated by the need for social distancing during the pandemic. It's now relatively common to have a consultation by video call, and we expect this will stay integral to health services going forward.

Healthcare hasn't escaped the hype around artificial intelligence either. There are opportunities in drug discovery, diagnostics and the delivery of patient care, but this is still early days.

Drug development is lengthy and expensive, with a low success rate. Companies that focus on these need to spend a lot of cash, with no guarantee of a return.

And it's important to keep refilling the hopper as eventually the exclusivity you get for taking the initial risk lapses. This paves the way for generic competitors to enter the market. And there's always the chance competitors will develop more effective treatments.

In the near term, pressure on government finances could keep a lid on the level of expenditure committed to the healthcare sector.

The sector is dependent on the availability of highly-skilled doctors, nurses and research scientists. This can hamper the development and delivery of products and services as well as push up costs.

Healthcare is highly regulated and a crucial political battleground. There's growing pressure to bring down prices. Consolidation in the industry is attracting the eye of the competition authorities. And there arent guarantees that certain medicines will be reimbursed by state or private health insurers.

Safety of clinical trials and marketed medicines is another risk to watch. It can take years after a product launch for side effects to become apparent, and this leaves the sector open to legal claims which can be expensive.

While COVID-19 seems to be well managed for now, we can't rule out the emergence of aggressive or vaccine-resistant strains, which could bring huge disruption to the sector.

The healthcare sector has an impressive long-term growth record. A number of drivers are likely to prolong this trend, not least being population growth and increasing life expectancy.

Meanwhile, there's a need to improve patient access and bridge the gap in healthcare coverage between developed and developing nations.

It's also a sector that has significant barriers to entry, which we see as a key attraction for investors.

In recent years, many of the major breakthroughs in medicine have been made by smaller biotech companies. The winners among them have proved very rewarding for investors. But the challenging economic environment has seen the falling appetites to fund these riskier businesses.

We favour companies with good cash flows and strong balance sheets. This lets them build more diverse development pipelines. And also create the infrastructure needed to commercialise their science, meaning they get more of the profits.

It also allows them to take advantage of the funding gap for smaller industry participants, by cherry-picking companies and assets in spaces they think are attractive.

It's certainly an exciting space to be in, but also a complex one. Its important to make sure you understand what youre investing in before diving in and remember, there are no guarantees.

Investments and any income from them can fall as well as rise in value, so you could get back less than you invest. This isnt personal advice if youre not sure whats right for you, seek advice.

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Investing in healthcare where are the opportunities? - Hargreaves Lansdown

MetroHealth, Case Western Reserve University Cancer … – Newsroom MetroHealth

Dr. Wang Headshot

MetroHealth and Case Western Reserve University (CWRU) cancer researchers have solved a mystery surrounding a receptor protein that can suppress cancer or make it grow and spread. Their findings, detailing how and why the EphA2 receptor plays the roles of both cancer hero and villain, will be published in the journal Science November 16.

The team of researchers was led by Bingcheng Wang, PhD, Director of the MetroHealth Division of Cancer Biology and MetroHealth Research Institute Director of Basic Sciences.

Discoveries like this make it possible to treat cancer, said Dr. Wang, who also is the John A. and Josephine B. Wootton Endowed Chair of Research and professor at the Case Western Reserve School of Medicine and a member of the Case Comprehensive Cancer Center. As a cancer researcher, there is no greater accomplishment. Being asked to share this work with the scientific community through the prestigious journal Science is an honor. But the greatest reward is to know that we are making strides that will have a real impact on our own patients and others throughout world.

Dr. Wang, who has been studying the EphA2 receptor for 25 years, is recognized as a pioneer in the field. His lab has made several key discoveries around the receptor, which is overexpressed in solid tumors like prostate, breast, colon and lung cancers as well as the aggressive brain tumor glioblastoma.

In two landmark studies published in Nature Cell Biology in 2000 and 2001, Dr. Wangs lab was the first to make the groundbreaking discoveries that the EphA2 can suppress malignant behaviors of cancer cells. In 2009, his team reported in Cancer Cell that the same receptor also can have the opposite function after being modified by tumor-promoting proteins. The modified EphA2 causes cancer cells to proliferate, maintain stem cell properties and metastasize to other parts of the body.

Now, after years of investigation, the researchers have figured out how EphA2 plays these dual, opposing roles in cancer. Using a cutting-edge spectroscopic platform (PIE-FCCS) that allows molecular analysis on live cells, they saw that EphA2 is automatically assembled into small clusters on live cells through two different types of interactions among adjacent EphA2 molecules that glue them together. One interaction contributes to the hero role and the other triggers the villain side of the molecule.

The first author of the paper is Dr. Xiaojun (Roger) Shi, a postdoctoral scholar at the CWRU School of Medicine and a current trainee with the Cancer Biology Training Program of the National Cancer Institute. Roger made the discovery by combining his expertise in molecular imaging during doctoral thesis work and mastery of experimental cancer biology gained in the Wang lab.

As the lead contact author, Dr. Wang shares the findings in the Science article Time-Resolved Live Cell Spectroscopy Reveals EphA2 Multimeric Assembly. A large multidisciplinary team contributed to the work. Dimitar B. Nikolov, of Memorial Sloan Kettering Cancer Center, and Adam W. Smith, of Texas Tech University, are co-corresponding authors of the paper. Khalid Sossey-Alaoui, of MetroHealth and CWRU; Matthias Buck, of CWRU; Ben Brown and Jens Meiler, of Vanderbilt University; and Dolores Hambardzumyan, of Icahn School of Medicine at Mount Sinai, are among the co-authors who contributed to the work. The paper will be published online by the journal Science on Thursday, November 16.

As the inaugural Director of the Division of Cancer Biology in the Department of Medicine, Dr. Wang has played a significant role in MetroHealths strategic vision for research, successfully recruiting several nationally recognized cancer researchers. In 2021, he led the formation of a new Cancer Research Team, funded through millions of dollars in support and grants, to focus on ending the racial, ethnic, social and economic inequities that impact cancer diagnosis and treatment.

We know that many types of cancer disproportionately affect people of color, said MetroHealth President & CEO Airica Steed, Ed.D, RN, MBA, FACHE. This is why we are hyperfocused on eradicating health disparities and will continue to support the cutting-edge research that leads to these discoveries, so eventually all patients who face a diagnosis of cancer can hope for a long life, regardless of their cultural background, where they live or how much money they make.

John Chae, MD, MetroHealth Senior Vice President, Chief Academic Officer, said Dr. Wangs discoveries and other pivotal research being done at MetroHealth are reinforcing the Systems reputation as a world-class research institution.

This is the sort of foundational research that life-saving therapies are built upon, said Dr. Chae, who also is Senior Associate Dean for Medical Affairs at the CWRU School of Medicine. We are fortunate to have internationally respected researchers like Dr. Wang and the incredible team he has assembled. We will go on supporting this research and proving that some of the very best science in the world is being done in Cleveland at The MetroHealth System.

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MetroHealth, Case Western Reserve University Cancer ... - Newsroom MetroHealth

3D Cell Culture Market to grow by USD 1.28 billion from 2021 to … – PR Newswire

NEW YORK, Nov. 13, 2023 /PRNewswire/ -- The3D cell culture market size is expected to grow by USD 1.28 billion from 2021 to 2026. In addition, the momentum of the market will be progressing at a CAGR of15.69% during the forecast period, according to Technavio Research.The market is segmented by application (Cancer and stem cell research, Drug discovery and toxicology testing, and Tissue engineering and regenerative medicine) and geography (North America, Europe, Asia, and Rest of World (ROW)).The 3D cell culture market share growth by cancer and stem cell research segment will be significant during the forecast period.The rising prevalence of cancer and significant funding for cancer research are significant factors that are anticipated to drive the growth of the segment in focus during the forecast period.This report offers an up-to-date analysis of the current market scenario, the latest trends and drivers, and the overall market environment. Read FREE PDF Sample Report

Company Profile:

3D Biotek LLC, BICO Group AB, CN Bio Innovations Ltd., Corning Inc., Elveflow, Emulate Inc., Greiner Bio-One International GmbH, Hamilton Bonaduz AG, InSphero AG, Lonza Group Ltd., Merck KGaA, PromoCell GmbH, QGel SA, REPROCELL Inc., Synthecon Inc., SynVivoInc., Tecan Group Ltd., Thermo Fisher Scientific Inc., TissUse GmbH, and MIMETAS BV

3D Biotek LLC -The company offers 3D Cell Culture products such as 3D cell culture devices.

To gain access to more vendor profiles available withTechnavio, buy the report

Learn about the contribution of each segment summarized in conciseinfographics and thorough descriptions. View a FREE PDF Sample Report

3D Cell Culture Market: Geographical Analysis

North Americais estimated toaccount for41%of the global market duringthe forecast period. The primary markets for 3D cell culture in North America are the US and Canada. In this region, market growth is expected to outpace that in Europe and the Rest of the World (ROW). This accelerated growth can be attributed to substantial investments in new manufacturing facilities made by major companies like Becton, Dickinson, and Company, Corning Incorporated, and Thermo Fisher Scientific Inc. Such investments are set to drive the expansion of the 3D cell culture market in North America during the forecast period.

3D Cell Culture Market: Driver & Trend:

The increase in infectious diseases is notably driving the market growth.

Identify key trends, drivers, and challenges in the market. Download FREE sample to gain access to this information.

What are the key data covered in this 3D cell culture market report?

Related Reports:

The GlobalCell Culture Marketsize is estimated togrowat aCAGR of 11.3%between 2022 and 2027. The size of the market is forecasted to increase byUSD 17.74 billion.

The cell culture consumables market size is estimated togrowat a CAGR of 22.3%between 2022 and 2027. The size of the cell culture market is forecast to increase byUSD 23,729.7 million.

ToC:

Executive Summary

Market Landscape

Market Sizing

Historic Market Sizes

Five Forces Analysis

Market Segmentation by Application

Market Segmentation by Geography

Customer Landscape

Geographic Landscape

Drivers,Challenges, &Trends

Company Landscape

Company Analysis

Appendix

About Technavio

Technavio is a leading global technology research and advisory company. Their research and analysis focus on emerging market trends and provide actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions.With over 500 specialized analysts, Technavio's report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning across 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavio's comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios.

Contacts

Technavio Research Jesse Maida Media & Marketing Executive US: +1 844 364 1100 UK: +44 203 893 3200 Email:[emailprotected] Website:www.technavio.com

SOURCE Technavio

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3D Cell Culture Market to grow by USD 1.28 billion from 2021 to ... - PR Newswire

New study reveals the critical role of microglia in human brain … – EurekAlert

image:

Super-resolution image of human stem cell-derived Microglia cells with labeled mitochondria (yellow), nucleus (magenta), and actin filaments (cyan). These Microglia cells help in the maturation of neurons in human brain organoid models. Photo credit: A*STAR's SIgN

Credit: A*STAR's SIgN

An international team of scientists has uncovered the vital role of microglia, the immune cells in the brain that acts as its dedicated defense team, in early human brain development. By incorporating microglia into lab-grown brain organoids, scientists were able mimic the complex environment within the developing human brain to understand how microglia influence brain cell growth and development. This research represents a significant leap forward in the development of human brain organoids and has the potential to significantly impact our understanding of brain development and disorders. The study, iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer was published in Nature on 1 November 2023.

To investigate microglia's crucial role in early human brain development, scientists from A*STAR's Singapore Immunology Network (SIgN) led by Professor Florent Ginhoux, utilised cutting-edge technology to create brain-like structures called organoids, also known as mini-brains in the laboratory. These brain organoids closely resemble the development of the human brain. However, previous models were lacking in microglia, a key component of early brain development.

To bridge this gap, A*STAR researchers designed a unique protocol to introduce microglia-like cells generated from the same human stem cells used to create the brain organoids. These introduced cells not only behaved like real microglia but also influenced the development of other brain cells within the organoids.

A*STAR's Institute of Molecular and Cell Biology (IMCB)'s Dr Radoslaw Sobota and his team at the SingMass National Laboratory for Mass Spectrometry applied cutting edge quantitative proteomics approach to uncover changes in protein. Their analysis provided crucial insights into the protein composition of the organoids, further confirming the studys findings.

What sets this study apart is the discovery of a unique pathway through which microglia interact with other brain cells. The study found that microglia play a crucial role in regulating cholesterol levels in the brain.The microglia-like cells were found to contain lipid droplets containing cholesterol, which were released and taken up by other developing brain cells in the organoids. This cholesterol exchange was shown to significantly enhance the growth and development of these brain cells, especially their progenitors.

Cholesterol, makes up about 25% of the body's total cholesterol content, is abundantly present in the brain and is essential for the structure and function of neurons. Abnormal cholesterol metabolism has been linked to various neurological disorders, including Alzheimer's and Parkinson's Disease.

To investigate the roles of lipids in brain development and disease, researchers from the Department of Biochemistry at the Yong Loo Lin School of Medicine (NUS Medicine), led by Professor Markus Wenk, took on the crucial task of data acquisition, particularly in the field of lipidomics to draw valuable insights into the lipid composition and dynamics within the brain organoids containing microglia.

Using this information, another team from the Department of Microbiology and Immunology at NUS Medicine and led by Associate Professor Veronique Angeli, found that cholesterol affects the growth and development of young brain cells in human brain models. Microglia use a specific protein to release cholesterol, and when this process is blocked, it causes the organoid cells to grow more, leading to larger brain models. It has always been known that the microglia is key to brain development, however their precise role remains poorly understood. This finding from our team at the Department of Microbiology and Immunology is particularly impactful because we finally understand how cholesterol is transported. Our next focus will be finding out how we can regulate cholesterol release to optimise brain development and slow down, or prevent, the onset of neurological conditions, added Assoc Prof Veronique, who is also Director of the Immunology Translational Research Programme at NUS Medicine.

Moreover, Dr Olivier Cexus from the University of Surrey and formely at A*STAR, progressively deciphered the complex molecular interactions within the brain organoids using proteomic and lipidomic analysis. This provided valuable insights into the metabolic cross-talks involved in brain development and potential implications for diseases.

Together, these collective efforts were instrumental in deepening our understanding of the roles of microglia and the molecular components within brain organoids and its implications for human health.

Prof Florent Ginhoux, Senior Principal Investigator at A*STARs SIgN and Senior author of the study said, "Understanding the complex roles of microglia in brain development and function is an active area of research. Our findings not only advance our understanding of human brain development but also have the potential to impact our knowledge of brain disorders. This opens up new possibilities for future research into neurodevelopmental conditions and potential therapies."

Co-author of the study, Professor Jerry Chan, Senior Consultant, Department of Reproductive Medicine, KK Womens and Childrens Hospital, and Senior National Medical Research Council Clinician Scientist, added, There is currently a lack of tools to study how microglia interacts with the developing brain. This has hampered the understanding of microglia-associated diseases that play an important role during the early development of conditions such as autism, schizophrenia, and neurodegenerative diseases such as Alzheimers and Parkinsons disease.

The development of these novel microglia-associated brain organoids with same-donor pluripotent stem cells gives us an opportunity to study the complex interactions between microglia and neurons during early brain development. Consequentially, this may enable us to study the role of microglia in the setting of diseases and suggest ways to develop new therapies in time.

iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer

1-Nov-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Researchers chart the contents of human bone marrow – Science Daily

A team at Weill Cornell Medicine has mapped the location and spatial features of blood-forming cells within human bone marrow. Their findings confirm hypotheses about the anatomy of this tissue and provide a powerful new means to study diseases, ranging from noncancerous conditions, such as sickle cell anemia, to malignant conditions, such as acute leukemia, that affect bone marrow.

For the research described Sept. 29 in Blood, the investigators retrieved deidentified archival bone marrow samples from 29 patients at NewYork-Presbyterian/Weill Cornell Medical Center, generating a vast amount of data about the spatial relationships among their contents.

Creating images of bone marrow has been difficult historically, according to senior author Dr. Sanjay Patel, director of the Multiparametric In Situ Imaging (MISI) Laboratory in the Department of Pathology and Laboratory Medicine and an assistant professor of pathology and laboratory medicine at Weill Cornell Medicine. He and his colleagues overcame these challenges by devising a method for visualizing whole pieces of the tissue, then analyzing them with artificial intelligence (AI).

"We have been able to apply our approach to archival samples in a way that wasn't possible before," said Dr. Patel, who is also a hematopathologist at NewYork-Presbyterian/Weill Cornell Medical Center and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. He noted that they succeeded in identifying and determining the positions of about 1.5 million cells in all.

Visualizing the Elusive Birthplace of Blood

Our blood cells get their start in the bone marrow, where stem cells produce the progenitors that in turn generate red and white blood cells, as well as the wound-sealing fragments known as platelets. Errors in these processes can give rise to acquired diseases including cancers, such as leukemia, lymphoma, and multiple myeloma, and those, such as sickle cell anemia, present from birth.

Studying the birth of blood cells within their native environment in human tissues, however, has proven challenging. What's more, when bone marrow samples are collected, the preservation technique can degrade some nucleic acids and proteins within the cells they contain. And, to avoid bias, researchers need to capture images of an entire piece of tissue, generating a daunting amount of data.

Dr. Patel's team came up with a series of solutions. They started by gathering samples from the tissue archive within Weill Cornell Medicine's Department of Pathology and Laboratory Medicine. These one-to-two-centimeter-long pieces of tissue came from patients who had received biopsies, but who had turned out to be disease free. Researchers in the MISI lab tested a variety of immune proteins known as antibodies, selecting from a catalog of thoroughly-vetted markers used in routine clinical diagnostics, to see which most effectively tagged the contents of bone marrow to make them visible with their fluorescence-based imaging instrumentation.

Their collaborators at BostonGene Corporation, a medical bioinformatics company, then used AI to analyze the resulting images, picking out individual cells, such as stem cells and the platelet-producing megakaryocytes, as well as bone, fat and blood vessels. This technology allowed the team to wrangle an otherwise unmanageable amount of information into a sophisticated analysis, according to Dr. Patel.

A New Way to Investigate Diseases

Previous studies have suggested that, during normal blood cell development, stem and progenitor cells inhabit certain locations, near bone and blood vessels, where surrounding cells create environments critical for their normal function. More recently, some research has suggested that these cells also gather around megakaryocytes, large cells that give rise to platelets. The team's analysis confirmed these patterns, including for megakaryocytes, in human samples. However, when they took patients' age into account, they found the cells were no longer as closely associated with megakaryocytes, which also tended to be smaller in older patients.

While these findings contribute to scientists' understanding of normal bone marrow, Dr. Patel sees the new method's greatest potential in investigating diseases, particularly along the course of their evolution. For a few conditions, such as acute myeloid leukemia, researchers already have evidence that the spatial arrangement of stem and progenitor cells may be disrupted. This new method could open the door to studies that specifically explore such changes -- and to those testing new treatments and evaluating existing ones, according to Dr. Patel.

"I hope our work unlocks the imagination of people who study diseases related to the bone marrow," he said.

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Anti-aging molecule extends lifespan by improving cellular health – Earth.com

Researchers at the Buck Institute have made a significant breakthrough in the field of aging and disease with the discovery of a new drug-like molecule.

This molecule, known as MIC (Mitophagy-inducing compound), has been shown to extend lifespan and improve health in a variety of ways.

MIC operates by promoting healthy mitochondria through a process called mitophagy, which removes and recycles damaged mitochondria.

Mitochondria are crucial organelles in cells that produce energy, and their health is directly linked to overall cellular health and longevity.

The study demonstrated that this molecule extended the lifespan of C. elegans, a nematode worm frequently used in aging research.

MIC also improved mitochondrial function in mouse muscle cells and showed promise in ameliorating pathology in neurodegenerative disease models.

Mitochondrial dysfunction is known to play a role in various age-related diseases, including neurodegenerative disorders like Parkinsons and Alzheimers, cardiovascular diseases, metabolic disorders, muscle wasting, and cancer progression.

Despite the potential of treatments targeting mitochondrial dysfunction, none have been approved for human use to date.

The mitophagy-inducing compound is a coumarin, a type of naturally bioactive compound found in many plants and certain types of cinnamon.

Coumarins are known for their diverse health benefits, including anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihyperglycemic properties, and neuroprotective effects.

The discovery of the effects of MIC originated from a study on Parkinsons disease. A team of experts including Dr. Julie Andersen and Dr. Shankar Chinta were examining known enhancers of mitophagy in a mouse model.

The mitophagy-inducing compound emerged as a significant find in their research. Instead of immediately testing MIC in mice, the researchers opted to study its impact on overall aging and its mechanism of action using the C. elegans model.

This approach led to the discovery that MIC belongs to a different class of molecules that enhance the expression of a key protein in autophagy and lysosomal functions (TFEB).

The study, led by Dr. Andersen and research scientist Dr. Manish Chamoli, revealed that MIC activates the transcription factor TFEB, a master regulator of genes involved in autophagy and lysosomal functions. Autophagy is an intracellular recycling process vital for cellular health.

The research findings are significant as they show MICs potential in not only extending lifespan but also preventing mitochondrial dysfunction in mammalian cells, offering new avenues for treating various age-related diseases.

Theres a bottleneck in efforts to develop potential therapeutics in the field of geroscience, and the bottleneck is that we dont have enough molecules in the pipeline, said study senior co-author Dr. Gordon Lithgow.

MIC is a great candidate to bring forward given its therapeutic effect across multiple models and the fact that it is a naturally occurring molecule.

Anti-aging strategies encompass a variety of practices and research areas focused on slowing down or reversing the aging process. Here are some key areas:

This includes a balanced diet rich in antioxidants, regular physical activity, adequate sleep, and stress management. Avoiding smoking and excessive alcohol consumption also plays a critical role.

Using sunscreen to protect the skin from UV damage, along with regular use of moisturizers and anti-aging products like retinoids and peptides, can help maintain skin health.

These include hormone replacement therapies, cosmetic procedures like Botox or fillers, and plastic surgery. These methods should be approached cautiously and under medical supervision.

Some people use supplements like omega-3 fatty acids, vitamin D, coenzyme Q10, and others believed to have anti-aging effects. However, their effectiveness can vary and should be used judiciously.

Areas like telomere therapy, stem cell research, and gene editing are being explored for potential anti-aging benefits. While promising, many of these are still in the experimental stages.

Maintaining mental health and active social life is essential. Activities that stimulate the mind, like puzzles, reading, and learning new skills, along with regular social interaction, can contribute to longevity and quality of life.

Regular visits to healthcare professionals for check-ups can help in early detection and management of age-related diseases.

Certain foods are known for their potential anti-aging benefits, mainly due to their high antioxidant content and other beneficial nutrients. Heres a list of some of these foods:

Incorporating these foods into a balanced diet can contribute to overall health and potentially slow some aspects of the aging process. Its also important to maintain a diverse diet and consult with a healthcare professional, especially when making significant dietary changes.

The research is published in the journal Nature Aging.

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Pancreas gene finding gives new insights into human development … – EurekAlert

Understanding how the human pancreas develops is crucial to allow scientists to make insulin producingbeta cells in the quest to cure Type 1 diabetes. Now, scientists have made a unique and surprising discovery - a gene that is essential for making the pancreas in humans is not present in almost all other animals.

Beta cells within the pancreas produce insulin that regulate blood sugar. Every mammal needs the pancreatic beta-cells to survive. In established Type 1 diabetes there are no, or very few, working beta-cells.

The new finding, published in Nature Genetics, challenges assumptions about how the regulation of development evolves. Until now, scientists had assumed that genes essential for development of key organs and functions were highly conserved through evolution, meaning the genetic pathway remains the same between different species, from fish to humans. However, the gene, called ZNF808, is only found in humans, other apes such as chimpanzees and gorillas, and in some monkeys, such as macaques.

This Wellcome Trust-funded research was carried out by researchers at the University of Exeter Medical School, the University of Cambridge and the University of Helsinki in Finland. The study shows just how different humans can be to other animals often used in research, such as mice, emphasising the importance of studying the human pancreas.

Lead author Dr Elisa De Franco, of the University of Exeter Medical School, said: Our finding is really surprising this is the only example we know of where a gene that is fundamental to the development of an organ in humans and primates is not present in other animals. Youd expect a gene only found in primates to regulate a feature that is specific to primates, such as brain size, but it is not the case for this gene, which instead is involved in development of an organ shared by all vertebrates! We think this shows that there must have been an evolutionary shift in higher primates to serve a purpose.

Senior author Professor Andrew Hattersley, of the University of Exeter Medical School, said: One hypothesis that we are exploring is that the evolutionary benefit is to the pancreas in the fetus. Human babies are born through the pelvis, so they cannot stay in the uterus for a longtime as they would grow too large for birth. Instead to cope with being born early and needing to survive without continual feeding they need to be born with more fat than any other animal. This fat is laid down when the fetus pancreas produces more insulin. Our research has shown that human fetuses have more insulin-related growth than other animals.

Dr Nick Owens, of the University of Exeter Medical School, remarked This research really emphasises the importance of studying the human pancreas in order to understand and find new treatments for diabetes. Animal research is important, but it can only tell us so much. We know there are fundamental differences between humans and other animals, such as mice which are often the subject of research in this field. The human pancreas is different in how it looks, works and develops. Our genetic finding could help us understand why thats the case.

ZNF808 belongs to a family of recently evolved proteins which bind and switch off specific regions of the DNA which have also developed recently in evolutionary terms. These DNA regions were among the regions considered junk DNA with no meaningful purpose for decades, but new technology have recently allowed us to discover their functions. Our findings confirm that these regions of our DNA are playing important roles during human development.

Dr Michael Imbeault, from the University of Cambridge, said These findings show that genes like ZNF808, even if relatively recent in evolution, can have a crucial role in human development. ZNF808 is a member of the largest, but also least studied family of proteins that regulate our genome. There are hundreds of genes like ZNF808 in our DNA, many primate or even human specific, and our results demonstrate how these can be key players in human health..

The identification of ZNF808 as being involved in human pancreas development occurred after researchers at the University of Exeter examined genetic samples from patients recruited across the world who were born without a pancreas and found that they all had genetic changes resulting in loss of ZNF808. They then teamed up with colleagues at the University of Cambridge and Helsinki University to study the effect of ZNF808 loss using stem cells in the lab. The results showed that ZNF808 plays an important function early during human development when cells need to decide whether to become pancreas or liver.

Among those who shared their genetic samples was Tania Bashir, aged 12, from Luton. Her father Imran Bashir welcomed the Exeter teams progress. Having an answer to why this happened is important. Weve always wanted to know now we do. The next important step is to understand what this means to the future of science. My dream is that one day, scientists will be able to genetically modify a stem cell and grow a human pancreas, and implant that into Tania, and potentially cure her. I dont know if that will ever be possible, but I do know that this understanding is a crucial step forward.

Professor Timo Otonkoski from University of Helsinki remarked The input of people born without a pancreas was fundamental to this discovery. Nobody would have ever thought that ZNF808 played a role in pancreatic development if we hadnt found the changes in this gene in these patients. The ultimate goal of our research is for this knowledge to be translated into being able to manipulate stem cells to produce beta cells that can produce insulin in the laboratory. That could be the key to curing type 1 diabetes. Our finding is a significant step in understanding what makes the human pancreas unique, which could help progress this area.

The research was supported by the Wellcome Trust, Diabetes UK, and by the Exeter NIHR Biomedical Research Centre. The paper is entitled Primate-specific ZNF808 is essential for pancreatic development in humans and is published in Nature Genetics.

Tanias story

Tania Bashir, Twin 2, weighed just 1.1kg when she was born, via emergency caesarean section, five weeks premature, without a pancreas.

Her mother Saiqa said: From week 20 onwards the weekly scans were stressful. We were told there was a high chance that the smaller twin wouldnt make it, so we kept the fact we had a twin a secret from friends, family and even her other three siblings.

Tanias father Imran, a chartered hardware engineer in Luton, recalled: Tania weighed about as much as a bag of sugar; you could quite easily fit her in the palm of your hand They immediately realised she had neonatal diabetes, but she was also not growing or gaining weight. It took eight weeks of investigations, tests and scans to figure out she had no pancreas. Our lives have never been the same since.

As well as producing no insulin to control her blood sugar, Tania, now 12, does not produce the enzymes that break down fats, proteins and carbohydrates into smaller molecules such as triglycerides, amino acids, and sugars so they can pass through the intestine into the bloodstream. Today, with the support of her parents, she lives a relatively normal life, despite still needing a special liquid feed via a tube at night and permanently using an insulin pump. But her dad recalls the dark days of fear and uncertainty when she was small.

First, we were told she wouldnt survive till birth, then that she wouldnt survive the next few weeks I remember consciously thinking that I didnt want to get too attached, because one of us would have to be strong when she died. In the end, we stopped asking. You normally look to the medical professionals for answers, but because the condition was so rare, there just is not the experience in the UK or across the world. We were learning along with the medical professionals, pushing each other to find better solutions for Tania. We are really lucky to have a fantastic team at the Luton and Dunstable hospital.

Imran found a small network of families globally via Facebook, which provided some shared experience. When Tania was six months old, the family was connected to the research team at the University of Exeter, who specialise in genetic causes of diabetes. They visited the lab and Imran said: I remember thinking, I like what theyre trying to do here we could get an answer.

A decade later, through sequencing all the genes in Tanias DNA (a technique called whole exome sequencing) the Exeter team has identified a gene which is crucial to the development of the human pancreas and is only present in humans and some monkeys, but not in other mammals. Tanias genetic sample was one of just 13 of children born without a pancreas to enable this discovery.

Imran welcomed the progress. Having an answer is important. It draws a line under the question of why, but the journey is far from over. Unlike people with type 1 diabetes, Tanias immune system didnt attack her pancreas so a pancreas could function in her body. I believe that it might be possible to use this research to modify stem cells and grow a pancreas using Tanias own cells, which could be implanted into her. I know it sounds like science fiction, but 40 years ago, there was no such thing as the internet. Now we can share moments instantly across the world. Theres some amazing scientific progress going on in the world, and the work done by Exeter has brought us one step closer to making my dream possible.

Dr Elisa de Franco, of the University of Exeter Medical School, said: Our findings really show the importance of studying the DNA of people with rare diseases to understand how organs develop and function. We are immensely grateful to people like Tania and her family, without them none of this would be possible.

Case study

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Primate-specific ZNF808 is essential for pancreatic development in humans

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