Stem Cells make the cover of National Geographic

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Clive Svendsen, PhD, left, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and Samuel Sances, PhD, a postdoctoral fellow at the institute, with the January 2019 special edition of National Geographic. The magazine cover features a striking image of spinal cord tissue that was shot by Sances in his lab. Photo by Cedars-Sinai.

National Geographic is one of those iconic magazines that everyone knows about but few people read. Which is a shame, because it’s been around since 1888 and has helped make generations of readers aware about the world around them. And now, it’s shifting gears and helping people know more about the world inside them. That’s because a special January edition of National Geographic highlights stem cells.

The issue, called ‘The Future of Medicine’, covers a wide range of issues including stem cell research being done at Cedars-Sinai by Clive Svendsen and his team (CIRM is funding Dr. Svendsen’s work in a clinical trial targeting ALS, you can read about that here). The team is using stem cells and so-called Organ-Chips to develop personalized treatments for individual patients.

Here’s how it works. Scientists take blood or skin cells from individual patients, then using the iPSC method, turn those into the kind of cell in the body that is diseased or damaged. Those cells are then placed inside a device the size of an AA battery where they can be tested against lots of different drugs or compounds to see which ones might help treat that particular problem.

This approach is still in the development phase but if it works it would enable doctors to tailor a treatment to a patient’s specific DNA profile, reducing the risk of complications and, hopefully, increasing the risk it will be successful. Dr. Svendsen says it may sound like science fiction, but this is not far away from being science fact.

“I think we’re entering a new era of medicine—precision medicine. In the future, you’ll have your iPSC line made, generate the cell type in your body that is sick and put it on a chip to understand more about how to treat your disease.”

Dr. Svendsen isn’t the only connection CIRM has to the article. The cover photo for the issue was taken by Sam Sances, PhD, who received a CIRM stem cell research scholarship in 2010-2011. Sam says he’s grateful to CIRM for being a longtime supporter of his work. But then why wouldn’t we be. Sam – who is still just 31 years old – is clearly someone to watch. He got his first research job, as an experimental coordinator, with Pacific Ag Research in San Luis Obispo when he was still in high school.

 

 

 

 

 

 

Performance, Passion and Progress: and that’s just page one of our 2018 Annual Report

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It’s hard to sum up the activities and achievements of a year in a single document, let alone one that’s just 24 pages. But that’s what we have done in putting together our 2018 Annual Report.

It’s a look back at the year just gone, the highlights, the low lights (spoiler alert – there weren’t any) and the impact we had on the field of stem cell research. But it’s far more than that. It’s also a look ahead. A look at the challenges we face, and profiles of the people who are going to help us overcome those challenges and maintain our progress.

And people are truly at the heart of this report, from UC San Francisco’s Dr. Tippi MacKenzie who is on the front cover for her work in developing an in-utero treatment for the almost always fatal disorder alpha thalassemia major (and the photo of the baby and mom whose lives were changed by that therapy) to Rich Lajara on the back cover, the first person ever treated in a CIRM-funded clinical trial.

Inside are an array of simple images designed to reflect how we as a state agency have performed this year. The numbers themselves tell a powerful story:

  • 50 clinical trials funded to date, 7 this year alone
  • $2.6 billion in CIRM grants has been leveraged to bring in an additional $3.2 billion in matching funds and investments from other sources.
  • 1,180 patients have been involved in CIRM clinical trials

We know people don’t have a lot of time to read Annual Reports so we have made this as visually engaging and informative as possible. We want you to get a real sense of who we are, what we have done and who has helped us do that without you having to wade through a document the size of War and Peace (great book by the way – the Russians beat Napoleon).

We think we have a great story to tell. This Annual Report is one chapter in that story. We hope you like it.

 

Midwest universities are making important tools to advance stem cell research

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iPSCs are not just pretty, they’re also pretty remarkable

Two Midwest universities are making headlines for their contributions to stem cell research. Both are developing important tools to advance this field of study, but in two unique ways.

Scientists at the University of Michigan (UM), have compiled an impressive repository of disease-specific stem cell lines. Cell lines are crucial tools for scientists to study the mechanics of different diseases and allows them to do so without animal models. While animal models have important benefits, such as the ability to study a disease within the context of a living mammal, insights gained from such models can be difficult to translate to humans and many diseases do not even have good models to use.

The stem cell lines generated at the Reproductive Sciences Program at UM, are thanks to numerous individuals who donated extra embryos they did not use for in vitro fertilization (IVF). Researchers at UM then screened these embryos for abnormalities associated with different types of disease and generated some 36 different stem cell lines. These have been donated to the National Institute of Health’s (NIH) Human Embryonic Stem Cell Registry, and include cell lines for diseases such as cystic fibrosis, Huntington’s Disease and hemophilia.

Using one such cell line, Dr. Peter Todd at UM, found that the genetic abnormality associated with Fragile X Syndrome, a genetic mutation that results in developmental delays and learning disabilities, can be corrected by using a novel biological tool. Because Fragile X Syndrome does not have a good animal model, this stem cell line was critical for improving our understanding of this disease.

In the next state over, at the University of Wisconsin-Madison (UWM), researchers are doing similar work but using induced pluripotent stem cells (iPSCs) for their work.

The Human Stem Cell Gene Editing Service has proved to be an important resource in expediting research projects across campus. They use CRISPR-Cas9 technology (an efficient method to mutate or edit the DNA of any organism), to generate human stem cell lines that contain disease specific mutations. Researchers use these cell lines to determine how the mutation affects cells and/or how to correct the cellular abnormality the mutation causes. Unlike the work at UM, these stem cell lines are derived from iPSCs  which can be generated from easy to obtain human samples, such as skin cells.

The gene editing services at UWM have already proved to be so popular in their short existence that they are considering expanding to be able to accommodate off-campus requests. This highlights the extent to which both CRISPR technology and stem cell research are being used to answer important scientific questions to advance our understanding of disease.

CIRM also created an iPSC bank that researchers can use to study different diseases. The  Induced Pluripotent Stem Cell (iPSC) Repository is  the largest repository of its kind in the world and is used by researchers across the globe.

The iPSC Repository was created by CIRM to house a collection of stem cells from thousands of individuals, some healthy, but some with diseases such as heart, lung or liver disease, or disorders such as autism. The goal is for scientists to use these cells to better understand diseases and develop and test new therapies to combat them. This provides an unprecedented opportunity to study the cell types from patients that are affected in disease, but for which cells cannot otherwise be easily obtained in large quantities.

NIH-scientists are told to stop buying fetal tissue for research, highlighting importance of CIRM’s voter-created independence

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National Institutes of Health

The news that President Trump’s administration has told scientists employed by the National Institutes of Health (NIH) that they can’t buy any new human fetal tissue for research has left many scientists frustrated and worried.

The news has also highlighted the reason why voters created CIRM in the first place and the importance of having an independent source of funding for potentially life-saving research such as this.

The Trump administration imposed the suspension of all new acquisitions saying it wants to review all fetal tissue research funded by the federal government. The impact was felt immediately.

In an article on ScienceMag.com, Warner Greene, director of the Center for HIV Cure Research at the Gladstone Institutes in San Francisco, said the decision derailed collaboration between his lab and one at Rocky Mountain Laboratories in Hamilton, Montana. The research focused on an antibody that previous studies showed might prevent HIV from establishing reservoirs in the human body.

“We were all poised to go and then the bombshell was dropped. The decision completely knocked our collaboration off the rails. We were devastated.”

Right now, it’s not clear if the “halt” is temporary or permanent, or if it will ultimately be expanded beyond scientists employed by the NIH to all scientists funded by the NIH who use fetal tissue.

In 2001, President George W. Bush’s decision to impose restrictions on federal funding for embryonic stem cell research helped generate support for Proposition 71, the voter-approved initiation that created CIRM. People felt that stem cell research had potential to develop treatments and cures for deadly diseases and that if the federal government wasn’t going to support it then California would.

CIRM Board member, and Patient Advocate for HIV/AIDS, Jeff Sheehy says the current actions could have wide-reaching impact.

“While the initial focus of the emerging ban on the use of fetal tissue has been on projects related to HIV, this action undermines a spectrum of vital research initiatives that seek to cure multiple life-threatening diseases and conditions.  Many regenerative medicine cell-based or gene therapies require pre-clinical safety studies in humanized mice created with fetal tissue.  These mice effectively have human immune systems, which allows researchers to examine the effects of products on the immune system. Work to prevent and treat infectious diseases, including vaccine efforts, require this animal model to do initial testing. Development of vaccines to respond to actual threats requires use of this animal model.  This action could have damaging effects on the health of Americans.”

 

CIRM-funded research is helping unlock the secrets behind “chemo brain”

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Every year millions of Americans undergo chemotherapy. The goal of the treatment is to destroy cancer, but along the way more than half of the people treated lose something else. They suffer from something called “chemo brain” which causes problems with thinking and memory. In some cases it can be temporary, lasting a few months. In others it can last years.

Now a CIRM-funded study by researchers at Stanford has found what may be behind chemo brain and identifying potential treatments.

In an article on the Stanford Medicine News Center, senior author Michelle Monje said:

“Cognitive dysfunction after cancer therapy is a real and recognized syndrome. In addition to existing symptomatic therapies — which many patients don’t know about — we are now homing in on potential interventions to promote normalization of the disorders induced by cancer drugs. There’s real hope that we can intervene, induce regeneration and prevent damage in the brain.”

The team first looked at the postmortem brains of children, some of whom had undergone chemotherapy and some who had not. The chemotherapy-treated brains had far fewer oligodendrocyte cells, a kind of cell important in protecting nerve cells in the brain.

Next the team injected methotrexate, a commonly used chemotherapy drug, into mice and then several weeks later compared the brains of those mice to untreated mice. They found that the brains of the treated mice had fewer oligodendrocytes and that the ones they had were in an immature state, suggested the chemo was blocking their development.

The inner changes were also reflected in behavior. The treated mice had slower movement, showed more anxiety, and impaired memory compared to untreated mice; symptoms that persisted for up to six months after the injections.

As if that wasn’t enough, they also found that the chemo affected other cells in the brain, creating a kind of cascade effect that seemed to amplify the impaired memory and other cognitive functions.

However, there is some encouraging news in the study, which is published in the journal Cell. The researchers gave the treated mice a drug to reverse some of the side effects of methotrexate, and that seemed to reduce some of the cognitive problems the mice were having.

Monje says that’s where her research is heading next.

“If we understand the cellular and molecular mechanisms that contribute to cognitive dysfunction after cancer therapy, that will help us develop strategies for effective treatment. It’s an exciting moment.”

 

CIRM invests $1.3 million to study stem cells in metabolic liver disease

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Dr. Tracy Grikscheit. Image courtesy of Children’s Hospital LA.

Metabolic liver disease, is an emerging public health concern in Western countries, but has largely been overshadowed by health issues such as cancer and diabetes. Chronic liver disease (of which metabolic liver disease is a significant contributor) however, is a significant public health concern, evidenced by its contribution to nearly 2 million deaths per year worldwide.

The primary treatment option for metabolic liver disease is a liver transplant. In fact, of the liver transplants performed every year, 14% are due to damage associated with metabolic disorders. With any organ transplant, however, such a procedure comes with drawbacks, the most frustrating of which is the need for patients to wait for an organ donor.

As transplants are not a reasonable or feasible option for many people, alternative treatment options are necessary.  Enter Dr. Tracy Grikscheit, a doctor-scientist at the Children’s Hospital Los Angeles, who hopes to make liver transplant a thing of the past for the millions of people who live with metabolic liver disease.

Dr. Grikscheit was awarded a $1.3 million grant to study how stem cells can be used to treat liver disease caused by metabolic disorders. In a press release, Dr. Grikscheit details the importance and practicality of using stem cells to treat liver disease:

“Liver-based metabolic diseases are the perfect starting point to apply cellular therapy to liver disorders. The only current therapy — a liver transplant — is costly and in short supply. Plus, it requires suppressing the patient’s immune system, which has long-term consequences.”

The project, termed UPLiFT for Universal Pluripotent Stem Cell Therapy, aims to use pluripotent stem cells (cells that can turn into any cell in the body) to correct liver associated disorders like Crigler-Najjar Syndrome. A genetic mutation in liver cells of these patients makes them unable to covert bilirubin (a byproduct of red blood cell degradation) to its non-toxic form. Dr. Grikscheit hopes to bypass the need for a liver transplant by giving these patients pluripotent stem cells that can become liver cells without the genetic mutation, and are able to convert bilirubin to its non-toxic form. The use of pluripotent stem cells would also potentially eliminate the need for lifelong immunosuppressive therapy

Dr. Grikscheit will use the CIRM grant to test safety and efficacy of the stem cell treatment in pre-clinical trials to determine the optimal cell dosage that will be both safe and relieve disease symptoms, as well as assessing any off-target effects of the treatment. She has previously received a grant from CIRM to study stem cell therapy options for digestive neuromuscular condition, which you can read about here.

 

Stories that caught our eye: SanBio’s Traumatic Brain Injury trial hits its target; A new approach to endometriosis; and a SCID kid celebrates Halloween in style

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Traumatic brain injury: graphic courtesy Brainline.org

Hopeful signs for treating brain injuries

There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.

In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.

In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”

CIRM did not fund this research but we are partnering with SanBio on another clinical trial targeting stroke.

 

Using a woman’s own cells to heal endometriosis

Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.

There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.

The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.

In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:

“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”

The study is published in the journal Stem Cell Reports.

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Happy Halloween from a scary SCID kid

A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.

That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.

Fortunately Ja’Ceon was enrolled in a CIRM-funded clinical trial at UC San Francisco where his own blood stem cells were genetically modified to correct the problem.

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Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.

Mechanical forces are the key to speedy recovery after blood cancer treatment

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Mesenchymal stem cells grown on a surface with specialized mechanical properties. Image courtesy of Krystyn Van Vliet at MIT.

Blood cancers, such as leukemia and lymphoma, are projected to be responsible for 10% of all new cancer diagnoses this year. These types of cancers are often treated by killing the patient’s bone marrow (the site of blood cell manufacturing), with a treatment called irradiation. While effective for ridding the body of cancerous cells, this treatment also kills healthy blood cells. Therefore, for a time after the treatment, patients are particularly vulnerable to infections, because the cellular components of the immune system are down for the count.

Now scientists at MIT have devised a method to make blood cells regenerate faster and  minimize the window for opportunistic infections.

Using multipotent stem cells (stem cells that are able to become multiple cell types) grown on a new and specialized surface that mimics bone marrow, the investigators changed the stem cells into different types of blood cells. When transplanted into mice that had undergone irradiation, they found that the mice recovered much more quickly compared to mice given stem cells grown on a more traditional plastic surface that does not resemble bone marrow as well.

This finding, published in the journal Stem Cell Research and Therapy, is particularly revolutionary, because it is the first time researchers have observed that mechanical properties can affect how the cells differentiate and behave.

The lead author of the study attributes the decreased recovery time to the type of stem cell that was given to mice compared to what humans are normally given after irradiation. Humans are given a stem cell that is only able to become different types of blood cells. The mice in this study, however, were give a stem cell that can become many different types of cells such as muscle, bone and cartilage, suggesting that these cells somehow changed the bone marrow environment to promote a more efficient recovery. They attributed a large part of this phenomenon to a secreted protein call ostepontin, which has previously been describe in activating the cells of the immune system.

In a press release, Dr. Viola Vogel, a scientist not related to study, puts the significance of these findings in a larger context:

“Illustrating how mechanopriming of mesenchymal stem cells can be exploited to improve on hematopoietic recovery is of huge medical significance. It also sheds light onto how to utilize their approach to perhaps take advantage of other cell subpopulations for therapeutic applications in the future.”

Dr. Krystyn Van Vliet, explains the potential to expand these findings beyond the scope of just blood cancer treatment:

“You could imagine that by changing their culture environment, including their mechanical environment, MSCs could be used for administration to target several other diseases such as Parkinson’s disease, rheumatoid arthritis, and others.”

 

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

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While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

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CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

Children’s Hospital of Los Angeles $1,297,512

 

DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

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Congresswoman Barbara Lee (D-CA 13th District)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

$93 million

$30 million

TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K

 

 

Sequencing data helps us understand the genes involved in heart cell development

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Human heart cells generated in the laboratory. Image courtesy of Nathan Palapant at the University of Queensland

Heart disease is the leading cause of death for both men and women in the United States and is estimated to be responsible for 31% of all deaths globally. This disease encompasses a wide variety of conditions that all effect how well your heart is able to pump blood to the rest of your body. One of the reasons that heart disease is so devastating is because, unlike many other organs in our bodies, heart tissue is not able to repair itself once it is damaged. Now scientists at the Institute for Molecular Bioscience at the University of Queensland and the Garvan Institute for Medical Research in Australia have conducted a tour de force study to exquisitely understand the genes involved in heart development.

The findings of the study are published in the journal Cell Stem Cell. in a press release, Dr. Nathan Palapant, one of the the lead authors, says this type of research could pay dividends for heart disease treatment because:

“We think the answers to heart repair almost certainly lie in understanding heart development. If we can get to grips with the complex choreography of how the heart builds itself in the first place, we’re well placed to find new approaches to helping it rebuild after damage.”

To determine which genes are involved in heart cell development, the investigators use a method called single cell RNA sequencing. This technique allowed them to measure how 17,000 genes (almost every gene that is active in the heart) were being turned on and off during various stages of heart cell development in 40,000 human pluripotent stem cells (stem cells that are capable of becoming any other cell type) experimentally induced to turn into heart cells.  This data set, the first of its kind, is a critical new resource for all scientists studying heart development and disease.

Interestingly, this study also addressed a commonly present, but rarely discussed issue with scientific studies: how applicable are results generated in vitro (in the lab) rather than the body, in the context of human health and disease? It is well known that heart cells generated in the lab do not have the exact same characteristics as mature heart cells found in our bodies, but the extent and precise nature of those discrepancies is not well understood. These scientists find that a gene called HOPX, which is one of earliest markers of heart cell development, is not always expressed when it should be during in vitro cardiac cell development, which, in turn, affects expression of other genes that are downstream of HOPX later on in development. Therefore, these scientists suggest that mis-expression of HOPX  might be one reason why in vitro heart cells express different genes and are distinct from heart cells in humans.

The scientists also learned that HOPX is responsible for controlling whether the developing heart cell moves past the “immature” dividing phase to the mature phase where cells grow bigger, but do not divide. This finding shows that this data set is powerful both for determining differences between laboratory grown cells versus mature human cells, but also provides critical biological information about heart cell development.

Joseph Powell, another lead author of this research, further explains how this work contributes to the important fundamentals of heart cell development:

“Each cell goes through its own series of complex, nuanced changes. They are all different, and changes in one cell affect the activity of other cells. By tracking those changes across the different stages of development, we can learn a huge amount about how different sub-types of heart cells are controlled, and how they work together to build the heart.”