Stem cells

CIRM CNS Consortium Workshop – Held Feb. 24 & 25, 2022

/ Mitra Hooshmand, PhD / 1 Comment

Note: Post edited to include post-event workshop videos. Watch both workshop videos here and here.

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Shared Stem Cell Laboratory at UCLA

Advance World Class Science, Deliver Real World Solutions, Provide Opportunity for All. 

These comprise the themes of our bold 5-year Strategic Plan. Since its launch less than two months ago, we have hit the ground running. Under the second and third strategic themes, we have already received ICOC approval for 2 concepts: Alpha Clinics Network Expansion and COMPASS educational program. We are now working on the execution of our first theme.  

As indicated in our Strategic Plan, we strongly believe advancing world class science relies on collaborative research that leverages collective scientific knowledge. To that end, we have organized the virtual CIRM CNS Consortium Workshop (click for the agenda and see registration details below) to help us gather feedback from a panel of experts about the best approach for promoting a culture of collaboration.

The vision for this workshop was informed by multiple layers of stakeholder discussions and input that started even prior to the passage of Proposition 14. A quick walk down memory lane reminds us of CIRM’s early and deliberate effort to identify areas of opportunity for promoting a paradigm shift with a “team science” approach, especially in the context of complex diseases such as those affecting the CNS: 

  • In 2019, we organized Brainstorming Neurodegeneration, a workshop where broad stakeholder input was received about the benefits and bottlenecks of developing a consortium approach where genomics and big data, novel stem cell models, and patient data could be collectively leveraged to advance the field of neurodegenerative research in a collaborative manner.  
  • In 2020, just before the passage of Prop 14 and based on input from the 2019 workshop, we already had our eyes on target: the future of collaborative research is in sharable data, and sharing petabytes or more of data requires a collaborative data infrastructure. To better understand the status and bottlenecks of knowledge platforms that could leverage data sharing, we brought together a panel of experts at our 2020 Grantee Meeting. We were encouraged to learn that our laser-focused approach for promoting knowledge sharing was right on target and the panelists suggested that CIRM has a great opportunity to promote a paradigm shift in this area.   
  • In early 2021, immediately after the passage of Prop 14 and building upon our previous conversations, we formed a Strategic Scientific Advisory Panel comprising a distinguished group of national and international scientists in the stem cell field. Once again, we were advised to expand sharable resources (especially in the context of stem cell modeling), bring more attention to complex diseases such as neurodegenerative and neuropsychiatric disorders, and facilitate knowledge sharing.  
  • In mid 2021, as we were forming our Strategic Plan based on the above input, we pressure-tested our paradigm-shifting vision in a Town Hall and further gathered feedback from California stakeholders about their needs. Again, all arrows pointed to shared resources and data as critical elements for accelerating research.  
CIRM Town Hall workshop hosted in 2021
  • Finally, in late 2021, just before the launch of our Strategic Plan, we organized a Data Biosphere Advisory Committee to advise us on ways to facilitate collaborative knowledge sharing. Here, we explored various models for leveraging and/or generating a data infrastructure in which CIRM-funded data could be managed and shared. The main outcome of this meeting was a recommendation to organize a workshop to test the feasibility and approach for generation of a CIRM knowledge platform. The Committee concluded that CIRM is uniquely positioned to contribute a wealth of data to the broader scientific community. A knowledge platform would provide an avenue for data sharing and collaboration with other groups that are dedicated to accelerating progress in the development of therapies, especially for CNS disorders.  

We were walking on solid ground! In December of 2021, paralleling the input we had received from experts and stakeholders, we launched our 5-year Strategic Plan with the goal of advancing world class science by promoting a culture of collaboration. 

To deliver on this goal, CIRM’s approach is to build the infrastructure (and we don’t mean bricks and mortar) that organizes and democratizes data through:  

  1. A network of shared resources labs that facilitate validation and standardization to support California regenerative medicine researchers  
  1. A data infrastructure where CIRM-funded data can be shared and external datasets leveraged to maximize real-world impact  
  1. We have held a virtual CNS Consortium Workshop on February 24th and 25th where we explored the development of these two resources through the deployment of a consortium and starting in the CNS space as a use case. While the discussions at the workshop centered on the CNS, the shared resources labs will be implemented across cell types and organs. The Data Infrastructure is intended to be a global resource for data sharing and fostering a culture of open science for all CIRM grantees—and the world. The complete workshop agenda can be found here.  

    Watch video recordings of Day 1 and Day 2 of the CNS workshop.

CIRM-funded stem cell clinical trial patients: Where are they now?

/ Esteban Cortez / Leave a comment
Ronnie with his parents Pawash Priyank and Upasana Thakur.

Since its launch in 2004, the California Institute for Regenerative Medicine (CIRM) has been a leader in growing the stem cell and regenerative medicine field while keeping the needs of patients at the core of its mission. 

To date, CIRM has:  

  • Advanced stem cell research and therapy development for more than 75 diseases. 
  • Funded 76 clinical trials with 3,200+ patients enrolled. 
  • Helped cure over 40 children of fatal immunological disorders with gene-modified cell therapies. 

One of these patients is Ronnie, who just days after being born was diagnosed with severe combined immunodeficiency (SCID), a rare immune disorder that is often fatal within two years. 

A recent photo of Ronnie enjoying a day at the beach.

Fortunately, doctors told his parents about a CIRM-funded clinical trial conducted by UC San Francisco and St. Jude Children’s Hospital. Doctors took some of Ronnie’s own blood stem cells and, in the lab, corrected the genetic mutation that caused the condition. They then gave him a mild dose of chemotherapy to clear space in his bone marrow for the corrected cells to be placed and to grow. Over the next few months, the blood stem cells created a new blood supply and repaired Ronnie’s immune system. He is now a happy, healthy four-year-old boy who loves going to school with other children. 

Evie Junior participated in a CIRM-funded clinical trial in 2020. Photo: Jaquell Chandler

Another patient, Evie Junior, is pioneering the search for a cure for sickle cell disease: a painful, life-threatening condition.  

In July of 2020, Evie took part in a CIRM-funded clinical trial where his own blood stem cells were genetically modified to overcome the disease-causing mutation. Those cells were returned to him, and the hope is they’ll create a sickle cell-free blood supply. Evie hasn’t had any crippling bouts of pain or had to go to the hospital since his treatment.

To demonstrate treatment efficacy, study investigators will continue to monitor the recovery of Evie, Ronnie, and others who participate in clinical trials. 

CIRM’s new strategic plan seeks to help real life patients like Ronnie and Evie by optimizing its clinical trial funding partnership model to advance more therapies to FDA for approval.  

In addition, CIRM will develop ways to overcome manufacturing hurdles for the delivery of regenerative medicine therapies and create Community Care Centers of Excellence that support diverse patient participation in the rapidly maturing regenerative medicine landscape. Stay tuned as we cover these goals here on The Stem Cellar. 

To learn more about CIRM’s approach to deliver real world solutions for patients, check out our new 5-year strategic plan.  

The Most Read Stem Cellar Blog Posts of 2021

/ Esteban Cortez / Leave a comment

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This year was a momentous one for the California Institute for Regenerative Medicine (CIRM). We celebrated the passage of Proposition 14, and as a result, introduced our new strategic plan and added a group of talented individuals to our team.  

We shared our most exciting updates and newsworthy stories—topics ranging from stem cell research to diversity in science—right here on The Stem Cellar. Nearly 100,000 readers followed along throughout the year! 

In case you missed them, here’s a recap of our most popular blogs of 2021. We look forward to covering even more topics in 2022 and send a sincere thank you to our wonderful Stem Cellar readers for tuning in!  

Image courtesy of ViaCyte
  1. Type 1 Diabetes Therapy Gets Go-Ahead for Clinical Trial 
    This past year, ViaCyte and CRISPR Therapeutics put their heads together to develop a novel treatment for type 1 diabetes (T1D). The result was an implantable device containing embryonic stem cells that develop into pancreatic progenitor cells, which are precursors to the islet cells destroyed by T1D. The hope is that when this device is transplanted under a patient’s skin, the progenitor cells will develop into mature insulin-secreting cells that can properly regulate the glucose levels in a patient’s blood. 
CIRM’s new General Counsel Kevin Marks
  1. CIRM Builds Out World Class Team With 5 New hires 
    After the Passage of Proposition 14 in 2020, CIRM set ambitious goals as part of our new strategic plan. To help meet these goals and new responsibilities, we added a new group of talented individuals with backgrounds in legal, finance, human resources, project management, and more. The CIRM team will continue to grow in 2022, as we add more team members who will work to fulfil our mission of accelerating world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and world. 
Image source: Doug Blackiston
  1. Meet Xenobots 2.0 – the Next Generation of Living Robots 
    In 2020, we wrote about how researchers at the University of Vermont and Tufts University were able to create what they call xenobots – the world’s first living, self-healing robots created from frog stem cells. Fast forward to 2021: the same team created an upgraded version of these robots that they have dubbed Xenobots 2.0. These upgraded robots can self-assemble a body from single cells, do not require muscle cells to move, and demonstrate the capability to record memory. Interesting stuff! 
Pictured: Clive Svendsen, Ph.D.
  1. CIRM Board Approves New Clinical Trial for ALS 
    In June, CIRM’s governing Board awarded $11.99 million to Cedars-Sinai to fund a clinical trial for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Clive Svendsen, Ph.D. and his team will be conducting a trial that uses a combined cell and gene therapy approach as a treatment for ALS. The trial builds upon CIRM’s first ALS trial, also conducted by Cedars-Sinai and Svendsen. 
Image courtesy of Karolina Grabowska
  1. COVID is a Real Pain in the Ear 
    Viral infections are a known cause of hearing loss and other kinds of infection. That’s why before the pandemic started, Dr. Konstantina Stantovic at Massachusetts Eye and Ear and Dr. Lee Gherke at MIT had been studying how and why things like measles, mumps and hepatitis affected people’s hearing. After COVID hit, they heard reports of patients experiencing sudden hearing loss and other problems, so they decided to take a closer look. 

And there you have it: The Stem Cellar’s top blog posts of 2021! If you’re looking for more ways to get the latest updates from The Stem Cellar and CIRM, follow us on social media on Facebook, Twitter, LinkedIn, and Instagram. 

Newly-developed Organoid Mimics How Gut and Heart Tissues Arise Cooperatively From Stem Cells 

/ Esteban Cortez / 1 Comment
Microscopy image of the new type of organoid created by Todd McDevitt, Ana Silva, and their colleagues in which heart tissue (red, purple, and orange masses) and gut tissue (blue and green masses) are growing together. Captured by Ana Silva.
Microscopy image of the new type of organoid created by Todd McDevitt, Ana Silva, and their colleagues in which heart tissue (red, purple, and orange masses) and gut tissue (blue and green masses) are growing together. Captured by Ana Silva. Image courtesy of Gladstone Institutes.

Scientists at Gladstone Institutes have discovered how to grow a first-of-its-kind organoid—a three-dimensional, organ-like cluster of cells—that mimics how gut and heart tissues arise cooperatively from stem cells.  

The study was supported by a grant from CIRM and the Gladstone BioFulcrum Heart Failure Research Program. 

Gladstone Senior Investigator Todd McDevitt, PhD said this first-of-its-kind organoid could serve as a new tool for laboratory research and improve our understanding of how developing organs and tissues cooperate and instruct each other. 

McDevitt’s team creates heart organoids from human induced pluripotent stem cells, coaxing them into becoming heart cells by growing them in various cocktails of nutrients and other naturally occurring substances. In this case, the scientists tried a different cocktail to potentially allow a greater variety of heart cells to form. 

To their surprise, they found that the new cocktail led to organoids that contained not only heart, but also gut cells. 

“We were intrigued because organoids normally develop into a single type of tissue—for example, heart tissue only,” says Ana Silva, PhD, a postdoctoral scholar in the McDevitt Lab and first author of the new study. “Here, we had both heart and gut tissues growing together in a controlled manner, much as they would in a normal embryo.” 

Shown here is the study’s first author, Ana Silva, a postdoctoral scholar in the McDevitt Lab. Image courtesy of Gladstone Institutes.

The researchers also found that compared to conventional heart organoids, the new organoids resulted in much more complex and mature heart structures—including some resembling more mature-like blood vessels. 

These organoids offer a promising new look into the relationship between developing tissues, which has so far relied on growing single-tissue organoids separately and then attempting to combine them. Not only that, the organoids could help clarify how the process of human development can go wrong and provide insight on congenital disorders like chronic atrial and intestinal dysrhythmias that are known to affect both heart and gut development. 

“Once it became clear that the presence of the gut tissue contributed to the maturity of the heart tissue, we realized we had arrived at something new and special,” says McDevitt. 

Read the official release about this study on Gladstone’s website. 

The study findings are published in the journal Cell Stem Cell.

Them bones them bones them dry bones – and how to help repair them

/ Kevin McCormack / 1 Comment

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Broken bones

People say that with age comes wisdom, kindness and confidence. What they usually don’t say is that it also comes with aches and pains and problems we didn’t have when we were younger. For example, as we get older our bones get thinner and more likely to break and less likely to heal properly.

That’s a depressing opening paragraph isn’t it. But don’t worry, things get better from here because new research from Germany has found clues as to what causes our bones to become more brittle, and what we can do to try and stop that.

Researchers at the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have identified changes in stem cells from our bone marrow that seem to play a key role in bones getting weaker as we age.

To explain this we’re going to have to go into the science a little, so bear with me. One of the issues the researchers focused on is the role of epigenetics, this is genetic information that doesn’t change the genes themselves but does change their activity. Think of it like a light switch. The switch doesn’t change the bulb, but it does control when it’s on and when it’s off. So this team looked at the epigenome of MSCs, the stem cells found in the bone marrow. These cells play a key role in the creation of cartilage, bone and fat cells.

In a news release, Dr. Andromachi Pouikli, one of the lead researchers in the study, says these MSCs don’t function as well as we get older.

“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice. We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”

So, they took some stem cells from the bone marrow of mice and tested them with a solution of sodium acetate. Now sodium acetate has a lot of uses, including being used in heating pads, hand warmers and as a food seasoning, but in this case the solution was able to make it easier for enzymes to get access to genes and boost their activity.

“This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.

So far so good. But does this work the same way in people? Maybe so. The team analyzed MSCs from people who had undergone hip surgery and found that they showed the same kind of age-related changes as the cells from mice.

Clearly there’s a lot more work to do before we can even think about using this finding as a solution to aging bones. But it’s an encouraging start.

The study is published in the journal Nature Aging.

Using a stem cell’s journey to teach kids science

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As far as Aldo Pourchet is concerned you are never too young to learn about stem cells. Aldo should know. He’s a molecular and cellular biologist and the co-founder and CEO of Omios Bio, which develops immunotherapies for cancer, infectious and inflammatory diseases.

Aldo Pourchet

And now Aldo is the author of a children’s book about stem cells. The book is “Nano’s Journey! A Little Stem Cell Visits the Heart and Lungs.” It’s the story of Nano, a stem cell who doesn’t know what kind of cell she wants to be when she grows up, so she goes on a journey through the body, exploring all the different kinds of cell she could be.

It’s a really sweet book, beautifully illustrated, and written in a charming way to engage children between the ages of 5 and 8. I asked Aldo what made him want to write a book like this.

“I was interested in providing very general knowledge such as the principle of life, the basic logics of nature and at the same time to entertain. It was very important for it not to be a textbook.

“Why Stem cells? Because it is the most fascinating biology and they are at the origin of an organism and throughout its life play an essential role. They evolve and transform, so they have a story that unfolds. An analogy with children maybe. It’s easy to imagine children are like stem cells, trying to decide who they are, while adults are like differentiated cells because they have already decided.

“For the kids to appropriate the story, I thought that humanizing cells was important.  I wanted children to identify themselves with the cells and especially Nano, the little girl main character. It’s a book written for the children, in the first place. We tell the story at their level. Not try to bring them up to the level of life science.

Aldo says right from the start he had a clear idea of who he wanted the lead character to be.

“I think the world needs more female leaders, more female voices and influence in general and in every domain. So quite early it became natural for me that Nano would be a girl and also would have a strong character, curious and adventurous.

“Blasto came later because I was looking for a companion to share the adventure with Nano. Blasto is a fibroblast so he is not supposed to leave the Bone Marrow but fibroblasts are everywhere in our organism so I thought it was an acceptable stretch.

The drawings in the book are delightful, colorful and fun. Aldo says he had some ideas, rounded shapes for the cells for example and a simple design that reflected the fact that there are no lines in nature. Illustrator Jen Yoon took it from there:

“Based on Aldo’s direction and imagination, I envisioned the style like drawings on a chalkboard. Soft curves with rough textures. After that everything went smoothly. Following Nano’s journey with my iPad pencil, it felt like a boat ride at an amusement park.”

The books are written to be read aloud by parents, adults and teachers to kids. But, spoiler alert, we don’t find out what cell Nano decides to be in this book. She’s going to have more adventures in other books before she makes up her mind.

Stem cell therapy for diabetic foot ulcers shows promise in new study

/ Yimy Villa / 2 Comments

For individuals with diabetes, the body’s inability to properly control blood sugar levels can lead to a wide range of other problems as time passes. One major issue is a diabetic foot ulcer (DFU), an open sore or wound that is commonly located on the bottom of the foot and caused by poor blood circulation and nerve damage. It occurs in approximately 15% of individuals with diabetes and in severe cases can lead to foot or leg amputation. Unfortunately, there is usually no effective form of treatment for this condition.

However, results from several studies authorized by the Ministry of Health of Nicaragua showed that using a stem cell therapy to treat patients with DFUs was safe and could be beneficial to patients.

The first results in a pilot study after an 18-month period demonstrated safety of the therapy and complete wound healing by nine months. After the six-year mark, five of the initial 10 subjects still demonstrated persistence of clinical benefits. It should be noted that five had passed away due to cardiac and other non-study-related causes.

In another study, the team wanted to determine the safety and efficacy of the stem cell therapy to treat non-healing DFUs greater than 3 centimeters in diameter.

For this clinical trial, 63 people from 35 to 70 years old with Type 2 diabetes and chronic DFU, all of whom were amputation candidates, were treated with a mixture of various types of stem cells obtained from the patient’s own fat tissue. The stem cell therapy was injected directly into the DFU with the hopes of restoring damaged blood vessels and promoting blood circulation and healing.

Patients were seen six months post treatment to evaluate ulcer closure, with 51 patients achieving 100 percent DFU closure and eight having greater than 75 percent. Only three required early amputations and one patient died. At 12 months post treatment, 50 patients had 100 percent DFU healing, while four had greater than 85 percent healing.

In a news release, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine, expressed interest in evaluating this stem cell therapy and results further.

“This work should be reviewed as it demonstrates the possibility of a novel cell injection therapy that can alleviate pain and infection, accelerate wound healing, and possibly avoid amputation.”

The full results of the recent study were published in Stem Cells Translational Medicine.

Meet xenobots 2.0 – the next generation of living robots

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Xenobots scurry about and can work together in swarms.
Source: Doug Blackiston

Last year we wrote about how researchers at the University of Vermont and Tufts University were able to create what they call xenobots – the world’s first living, self healing robots created from frog stem cells.

Now, the same team has created an upgraded version of these robots that they have dubbed Xenobots 2.0. These upgraded robots have the ability to self-assemble a body from single cells, do not require muscle cells to move, and demonstrate the capability to record memory. In comparison to the previous version developed, Xenobots 2.0 can move faster, navigate different environments, have longer lifespans, and still have the ability to work together in groups and heal themselves if damaged. 

To create Xenobots 2.0, researchers at Tufts University took stem cells from embryos from the African frog Xenopus laevis (which is where the name Xenobots is derived from). The team then allowed the stem cells to self assemble and grow into sphere-like shapes. In a few days, these newly formed stem cell spheroids produced tiny hair-like projections, allowing them to move back and forth or rotate in a specific way.

Meanwhile, scientists at the University of Vermont were running computer simulations that modeled different shapes of the Xenobots to see if they might exhibit different behaviors, both individually and in groups. The team ran hundreds of thousands of random environmental conditions using an evolutionary algorithm and used these simulations to identify the Xenobots most able to work together in swarms to gather large piles of debris in a field of particles. What they found was that Xenobots 2.0 are much faster and better at tasks such as garbage collection. They can also cover large flat surfaces or travel through narrow capillaries.

Using a fluorescent protein, Xenobots 2.0 record exposure to blue light by turning green. Source: Doug Blackiston

Going one step further for Xenobots 2.0, the researchers at Tufts University engineered the Xenobots in a way to enable them to record one bit of information. By introducing a fluorescent protein, they were able to get the Xenobots to glow green normally. However, if the Xenobots were exposed to blue light, they would start to glow red instead.

To test this memory function, the team allowed ten Xenobots to swim around a surface on which one spot is illuminated with a beam of blue light. After two hours, they found that three bots glowed red and the rest remained green, effectively recording their travel experience.

In a press release, robotics expert Josh Bongard from the University of Vermont who played an integral role in this study elaborated on what these findings could implicate.

“When we bring in more capabilities to the bots, we can use the computer simulations to design them with more complex behaviors and the ability to carry out more elaborate tasks. We could potentially design them not only to report conditions in their environment but also to modify and repair conditions in their environment.”

Xenobots 2.0 were also able to heal quite rapidly, closing the majority of a deep cut half their thickness within 5 minutes of the injury. All injured bots were able to ultimately heal the wound, restore their shape, and continue their work as before.

In the same press release, Dr. Michael Levin, professor at Tufts University and corresponding author of the study, had this to say.

“The biological materials we are using have many features we would like to someday implement in the bots – cells can act like sensors, motors for movement, communication and computation networks, and recording devices to store information. One thing the Xenobots and future versions of biological bots can do that their metal and plastic counterparts have difficulty doing is constructing their own body plan as the cells grow and mature, and then repairing and restoring themselves if they become damaged. Healing is a natural feature of living organisms, and it is preserved in Xenobot biology.”

The full results of this study were published in Science Robotics.

You can learn more about this research from Dr. Michael Levin by watching his TED Talk linked below:

New hydrogel developed could aid in therapies to generate bones in head and neck

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Taking a cue from mussels’ natural ability to adhere to surfaces underwater, the UCLA researchers incorporated an alginate-based solution in their hydrogel.
Photo taken by D. Jude, Univ. of Michigan

When most people think of mussels, what immediately comes to mind might be a savory seafood dish or favorite seafood restaurant. But to Dr. Alireza Moshaverinia and his team of researchers at the UCLA School of Dentistry, it’s the ability that mussels have to stick to wet surfaces that is of particular interest.

Partially inspired by this concept and with support from CIRM, the team of researchers developed the first adhesive hydrogel specifically to regenerate bone and tissue defects following head and neck injuries.

Over the past few years, surgeons and clinicians have began to use hydrogels to administer stem cells to help regenerate lost tissues and for bone defects. Hydrogels are beneficial because they can be effective at carrying stem cells to targeted areas inside the body. However, when used in surgeries of the mouth, they tend to become less effective because blood and saliva prevent them from properly adhering to the targeted site. As a result of this, the stem cells don’t stay in place long enough to deliver their regenerative properties.

To help with this problem, the researchers at UCLA developed a new hydrogel by adding alginate into the mix. Alginates are found in the cells of algae and form a sticky, gum-like substance when wet.

The scientists then tested their new hydrogel by loading it with bone building stem cells and applying it to the mouths of rats with an infectious disease that affects the bone structure. They then sealed the hydrogel in place and applied a light treatment, similar to what dentists use in humans to solidify dental fillings.

The results showed that the bone around the implants in all of the rats had completely regenerated.

In a news release from UCLA, Dr. Moshaverinia elaborates on what this study means for potential future treatments.

“The light treatment helped harden the hydrogel, providing a more stable vehicle for delivery of the stem cells. We believe that our new tissue engineering application could be an optimal option for patients who have lost their hard and soft craniofacial tissues due to trauma, infection or tumors.”

The full study was published in Science Translational Medicine.

Tiny organs grown from snake stem cells produce real venom

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Researchers grew tiny venom glands from nine different snake species, including the cape coral cobra pictured above.
Photo Credit: Michael D. Kern/Science Source

Snake venom can be deadly without proper treatment. Interestingly enough, it may also hold the key for treatments against pain, high blood pressure, and cancer according to one analysis. Despite this, scientists still do not understand much about the biology behind the wide range of different snake venoms, which can make it challenging to develop effective treatments in the event of snake bites.

Fortunately, a new study by Dr. Hans Clevers and his team at the Hubrecht Institute in the Netherlands could significantly aid the understanding of snake venom. Dr. Clevers and his team were able to grow miniature snake venom glands using snake stem cells. What’s more remarkable is that these “mini-organs” produced real venom!

Miniature, lab-grown snake venom glands
 Photo Credit: Ravian van Ineveld/Princess Maxima Center

In an article posted in Science Magazine, Dr. Clevers talks about how his study was navigating uncharted waters.

“Nobody knew anything about stem cells in snakes. We didn’t know if it was possible at all.”

To produce these “mini-organs”, the researchers removed the stem cells from the venom glands of nine different types of snake and placed them in a mixture of growth factors that contained different hormones and proteins. It turns out that the snake stem cells responded to the same factors used on human and mouse stem cells.

Eventually, the stem cells grew into little clumps of tissue and when the researchers removed the growth factors, they started to change into the same kind of cells that produce venom in the glands of snakes. Additionally, they were able to find that these “mini-organs” expressed similar genes as those observed in real venom glands.

The scientists were even able to test the nature of the “mini-organ” venom as well. A chemical and genetic analysis of the venom revealed that it matched the one made by real snakes. After testing this venom on mouse muscle cells and rat neurons, they also found that it damaged these cells similar to real venom.

The type of toxins and concentration levels can vary drastically in snake venom, even within the same species. This can make developing treatments challenging since they can only be used to combat one type of venom.

Dr. Clevers and his team now plan to study the complexities of venom and venom glands by compiling a “biobank” of frozen organoids from venomous reptiles around the world that could help researchers find broader treatments. With the aid of their newly developed “mini-organs”, all of this can be done without the handling of live, dangerous snakes, some of which are rare and difficult to keep in captivity.

The full results of this study were published in Cell.