3D

Stanford scientists are growing brain stem cells in bulk using 3D hydrogels

/ Karen Ring / 1 Comment

This blog is the final installment in our #MonthofCIRM series. Be sure to check out our other blogs highlighting important advances in CIRM-funded research and initiatives.

Neural stem cells from the brain have promising potential as cell-based therapies for treating neurological disorders such as Alzheimer’s disease, Parkinson’s, and spinal cord injury. A limiting factor preventing these brain stem cells from reaching the clinic is quantity. Scientists have a difficult time growing large populations of brain stem cells in an efficient, cost-effective manner while also maintaining the cells in a stem cell state (a condition referred to as “stemness”).

CIRM-funded scientists from Stanford University are working on a solution to this problem. Dr. Sarah Heilshorn, an associate professor of Materials Science and Engineering at Stanford, and her team are engineering 3D hydrogel technologies to make it easier and cheaper to expand high-quality neural stem cells (NSCs) for clinical applications. Their research was published yesterday in the journal Nature Materials.

Stem Cells in 3D

Similar to how moviegoers prefer to watch the latest Star Wars installment in 3D, compared to the regular screen, scientists are turning to 3D materials called hydrogels to grow large numbers of stem cells. Such an environment offers more space for the stem cells to proliferate and expand their numbers while keeping them happy in their stem cell state.

To find the ideal conditions to grow NSCs in 3D, Heilshorn’s team tested two important properties of hydrogels: stiffness and degradability (or how easy it is to remodel the structure of the hydrogel material). They designed a range of hydrogels, made from proteins with elastic qualities, that varied in these two properties. Interestingly, they found that the stiffness of the material did not have a profound effect on the “stemness” of NSCs. This result contrasts with other types of adult stem cells like muscle stem cells, which quickly differentiate into mature muscle cells when exposed to stiffer materials.

On the other hand, the researchers found that it was crucial for the NSCs to be able to remodel their 3D environment. NSCs maintained their stemness by secreting enzymes that broke down and rearranged the molecules in the hydrogels. If this enzymatic activity was blocked, or if the cells were grown in hydrogels that couldn’t be remodeled easily, NSCs lost their stemness and stopped proliferating. The team tested two other hydrogel materials and found the same results. As long as the NSCs were in a 3D environment they could remodel, they were able to maintain their stemness.

NSCs maintain their stemness in hydrogels that can be remodeled easily. Nestin (green) and Sox2 (red) are markers that indicate “high-quality” NSCs. (Image courtesy of Chris Madl, Stanford)

Caption: NSCs maintain their stemness in hydrogels that can be remodeled easily. Nestin (green) and Sox2 (red) are markers that indicate “high-quality” NSCs. (Images courtesy of Chris Madl)

Christopher Madl, a PhD student in the Heilshorn lab and the first author on the study, explained how remodeling their 3D environment allows NSCs to grow robustly in an interview with the Stem Cellar:

Chris Madl

“In this study, we identified that the ability of the neural stem cells to dynamically remodel the material was critical to maintaining the correct stem cell state. Being able to remodel (or rearrange) the material permitted the cells to contact each other.  This cell-cell contact is responsible for maintaining signals that allow the stem cells to stay in a stem-like state. Our findings allow expansion of neural stem cells from relatively low-density cultures (aiding scale-up) without the use of expensive chemicals that would otherwise be required to maintain the correct stem cell behavior (potentially decreasing cost).”

To 3D and Beyond

When asked what’s next on the research horizon, Heilshorn said two things:

Sarah Heilshorn

“First, we want to see if other stem cell types – for example, pluripotent stem cells – are also sensitive to the “remodel-ability” of materials. Second, we plan to use our discovery to create a low-cost, reproducible material for efficient expansion of stem cells for clinical applications. In particular, we’d like to explore the use of a single material platform that is injectable, so that the same material could be used to expand the stem cells and then transplant them.”

Heilshorn is planning to apply the latter idea to advance another study that her team is currently working on. The research, which is funded by a CIRM Tools and Technologies grant, aims to develop injectable hydrogels containing NSCs derived from human induced pluripotent stem cells to treat mice, and hopefully one day humans, with spinal cord injury. Heilshorn explained,

“In our CIRM-funded studies, we learned a lot about how neural stem cells interact with materials. This lead us to realize that there’s another critical bottleneck that occurs even before the stage of transplantation: being able to generate a large enough number of high-quality stem cells for transplantation. We are developing materials to improve the transplantation of stem cell-derived therapies to patients with spinal cord injuries. Unfortunately, during the transplantation process, a lot of cells can get damaged. We are now creating injectable materials that prevent this cell damage during transplantation and improve the survival and engraftment of NSCs.”

An injectable material that promotes the expansion of large populations of clinical grade stem cells that can also differentiate into mature cells is highly desired by scientists pursuing the development of cell replacement therapies. Heilshorn and her team at Stanford have made significant progress on this front and are hoping that in time, this technology will prove effective enough to reach the clinic.

Scientists use cotton candy to make artificial blood vessels

/ Karen Ring / Leave a comment

Cotton candy gets a bad rap. The irresistible, brightly colored cloud of sugar is notorious for sending kids into hyperactive overdrive and wreaking havoc on teeth. While it’s most typically found at a state fair or at a sports stadium, cotton candy is now popping up at the lab bench and is re-branding itself into a useful tool that will help scientists develop artificial blood vessels for lab-grown organs.Pink_and_blue_cotton_candy

How is this sticky, sweet substance transitioning from stomachs to the lab? The answer comes from a Professor at Vanderbilt University, Dr. Leon Bellan. He develops 3D microfluidic materials for biomedical applications. Recently he and his students have tackled an obstacle that has plagued the fields of tissue engineering and 3D organ modeling – making enough blood vessels to keep engineered organs alive. The story was covered by the blog Inhabitat.

Scientists are using 3D organoids or “mini-organs” derived from stem cells to model organ development and human disease in a dish. While methods to make organoids have advanced to the point where various cell types of an organ are generated, these organoids do not develop a proper capillary system – a distribution of blood vessels that allows blood to bring water, oxygen and nutrients to tissue cells. Inevitably, cells located in the center of organoids die because they don’t have access to life-saving nutrients that the cells at the surface do.

Spinning cotton candy in the lab.

Bellan lab member spins cotton candy in the lab.

Bellan came up with a sweet solution to this problem. His team discovered that you can use cotton candy to make an artificial capillary system. Conveniently, the strands of cotton candy are similar in size to human blood vessels. Bellan and his team “spin” cotton candy fibers to generate a network of sugar strands that are held in place with a special polymer. Then, they pour a gelatinous mold over the strands, let that harden, and dissolve the sugar with an enzyme solution. What’s left is an intricate network of channels that are similar to the human capillary system.

Free of cotton candy, these artificial channels are now ready to be turned into functioning human capillaries. Bellan and his team were able to grow human endothelial cells (the cells that line your blood vessels) in these channels. The cells in these artificial blood vessels are able to survive for over a week.

cotton-candy-capillaries01-889x430

Gelatin mold with cotton candy made channels.

Their work is still preliminary but Bellan is excited about their technology’s potential for tissue engineering applications. In a video interview, he explained:

Leon Bellan. Photo by Joe Howell

Leon Bellan.
(Photo by Joe Howell)

“We’re really try to attack a fundamental hurdle for the entire field. The sci-fi version would be that you would like to be able to build an organ from scratch.”

 

Hopefully, Bellan and his group will be able to turn their sweet dream into a reality and help scientists develop properly functioning artificial organs that can be transplanted into humans.

To learn more about this fascinating technique, check out this video:

Related links:

CIRM Scholar Jessica Gluck on using stem cells to make biological pacemakers for the heart

/ Karen Ring / Leave a comment

As part of our CIRM scholar series, we feature the research accomplishments of students and postdocs that have received CIRM funding.

Jessica Gluck, CIRM Scholar

Jessica Gluck, CIRM Scholar

I’d like to introduce you to one of our CIRM Scholars, Jessica Gluck. She’s currently a Postdoctoral Fellow at UC Davis working on human stem cell models of heart development. Jessica began her education in textiles and materials science at North Carolina State University, but that developed into a passion for biomedical engineering and stem cell research, which she pursued during her PhD at UC Los Angeles. During her graduate research, Jessica developed 3D bio-scaffolds that help human stem cells differentiate into functioning heart cells.

We asked Jessica to discuss her latest foray in the fields of stem cells and heart development.

Q: What are you currently working on in the lab?

JG: I work as a postdoc at UC Davis in the lab of Deborah Lieu. She’s working on developing pacemaking cardiomyocytes (heart cells) from human induced pluripotent stem cells (iPS cells). Pacemaking cells are the cells of the heart that are in charge of rhythm and synchronicity. Currently, we’re able to take iPS cells and get them to a cardiomyocyte state, but we want to further develop them into a pacemaking cell.

So ultimately, we’re trying to make a biological pacemaker. We can figure out how we can make a cell become the cell that tells your heart to beat, and there’s two things we can get out of that. First, if we understand how we get these beating cells, the ones that are telling the other heart cells to beat, we might be able to understand how different heart diseases progress, and we might be able to come up with a new way to prevent or treat that disease. Second, if we understand how we’re getting these pacemaking cells, we could hopefully bioengineer a biological pacemaker so you wouldn’t necessarily need an electronic pacemaker. With a biological one, a patient wouldn’t have to go back to the doctor to have their battery replaced. And they wouldn’t have to have multiple follow up surgeries throughout their life.

Q: What models are you using to study these pacemaking cells?

JG: I’m looking at my project from two different directions. On one side, we’re using a pig model, and we’re isolating cells from the sinoatrial (SA) node, which is where the pacemaking cells actually reside in your heart. And there’s really not that many of these cells. You probably have about a billion cells in your heart, but there’s maybe 100,000 of these pacemaking cells that are actually controlling the uniform beating of the heart. So we’re looking at the native SA node in the pig heart to see if it’s structurally any different than ventrical or atrial heart tissue.

Diagram of the heart depicting the Sinoatrial Node. (Image from Texas Heart Institute.

Diagram of the heart depicting the Sinoatrial Node. (Image from Texas Heart Institute)

We’ve found that the SA node is definitely different. So we’re de-cellularizing that tissue (removing the cells but not the matrix, or support structure, that keeps them in place) thinking that we could use the native matrix as a scaffold to help guide these heart cells to become the pacemaking phenotype. On the other side, we’re taking dishes with a known elasticity and we’re coating them with different proteins to see if we can tease out if there’s something that an individual protein does or a certain stiffness that actually is part of the driving force of making a pacemaking cell. We’ve gotten some pretty good preliminary results. So hopefully the next phase will be seeing how functional the cells are after they’ve been on these de-cellularized matrices.

Q: Why does your lab work with pig models?

JG: Pig hearts are pretty close to the human heart – their anatomy is pretty similar. To give you context, a pig heart is slightly larger than the size of your two hands clasped together. But the SA node, when you isolate it out, is only a couple of millimeters squared. It’s a lot smaller than we originally thought, and if we had gone with a smaller animal model, we wouldn’t be able to tangibly study or manipulate the SA node area. Because we are at UC Davis, we have a Meat Lab on campus, and we are able to get the pig hearts from them.

Q: Have you run into any road blocks with your research?

JG: For anybody that’s working with cardiomyocytes, the biggest problem is getting stem cells to become mature cardiomyocytes. Some labs have shown that you can get cells to a more mature cardiomyocyte after it’s been in culture for almost 100 days, but that’s not exactly feasible or that helpful.

We’ve been able to isolate out a small population of cells that we’re pretty sure are pacemaking cells. Over the last year, we’ve realized that a lot of the information that we thought we knew about pacemaking cells isn’t necessarily specific to pacemaking cells. Many of the biological markers that people have published in the literature are present in pacemaking cells, but we realized that they are also present in other heart cells like atrial cells, just in a lower amount. So we haven’t really been able to pick one specific biomarker that we’ve been able to say, yes this is actually a pacemaking cell. Instead, we have a small percentage of cells that we’re able to study. But we’re trying to figure out if there’s a way that we could increase our yield, or if there’s something fundamentally different about the environment that would also increase the yield of these pacemaking cells. So we’ve had a lot of trouble shooting along the way.

Q: What was your experience like as a CIRM scholar?

JG: I became a CIRM scholar in the spring of 2014. It was through the UC Davis Stem Cell Training Program. The opportunity was very helpful for me because it was in my first year as a postdoc at Davis. I earned my PhD at UCLA, so I was dealing with being on a new campus, trying to figure out whose lab I could go to to borrow random things and where to find equipment that I needed to use. So it was helpful to be around a group of other people that were also doing stem cell projects. Even though a lot of us were focused on different areas, it was still helpful to talk to other people, especially if you get somebody’s perspective that isn’t necessarily in your field. They might come up with a random idea that you haven’t thought of before.

Over the course of the year, we had a journal club, which was always interesting to see what’s going on in the field. I also went to the annual International Society for Stem Cell Research meeting in Vancouver using CIRM funding. And as part of the program, we also worked with the CIRM Bridges program between UC Davis and Cal State Sacramento. There were Bridges master’s students that were there with us. It was interesting to hear their take on everything, and they were very enthusiastic. We have had two master’s students work in our lab. I think it was very beneficial to them because they got a lot of hands on training and both have gone on to jobs in the regenerative medicine field.

Q: What is the future of stem cell research?

JG: If you’re looking at heart disease and stem cell treatments, there’s been some interesting clinical trials that have come out that have some promising results. I think that for a couple of those studies, people might have jumped the gun a little getting the treatments into the clinic. There’s still a lot that people should study in the lab before we move on to clinical trials. But I do think that we will see something in the next 20 years where stem cell research is going to have a huge therapeutic benefit. The field is just moving so quickly, and I think it will be really interesting to see what advances are made.

For our research, I’ve always been fairly realistic, and unfortunately, I don’t think we will see this biological pacemaker any time soon. But I think that the research that we produce along the way will be very beneficial to the field and our work will hopefully improve the foundation of what is known about pacemaking cells. What I think is really interesting about our lab’s work, is that we are moving into a 3D culture environment. Cells behave very differently in the body as opposed to on a plastic petri dish. So I think it’s very encouraging that we are seeing a lot more labs moving towards a more physiologically relevant model.

Q: What are your future goals?

I’ve been lucky that I’ve been able to work with very well established professors and also brand new faculty. But I’ve seen how difficult the funding climate is – it’s very daunting. So I’m really not sure what will happen next, and I’m keeping my options open.

I’ve really enjoyed working with our undergraduate and graduate students. I’ve gotten involved with outreach programs in Sacramento that promote science to young kids. It’s something that I’ve really enjoyed, and it’s very interesting telling people that I work in stem cells. Middle school kids seem to think that stem cells are magic. It’s fun to explain the very basics of stem cells and to see the light bulb moment where they understand it. I’m hoping to end up in a career that is still within the stem cell field but more towards teaching or outreach programs.

Q: What is your favorite thing about being a scientist?

JG: The thing I really like is having a puzzle that you’re trying to figure out the answer to. It’s great because every time you answer one question, that answer is going to lead you to at least three or four more new questions. I think that that’s really interesting especially trying to figure out how all the puzzle pieces fit together, and I’ve really enjoyed getting to work with people in very different fields. My parents think its funny because they said even as a little kid, I hated not knowing the answers to questions – and still do! They were completely understanding as to why I stayed in school as long as I did.

You can learn more about Jessica’s research by following her on Twitter: @JessicaGluckPhD

Stem cell stories that caught our eye: watching tumors grow, faster creation of stem cells, reducing spinal cord damage, mini organs

/ Don Gibbons / Leave a comment

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Video shows tumors growing. A team at the University of Iowa used video to capture breast cancer cells recruiting normal cells to the dark side where they help tumors grow.

Led by David Soll, the team reports that cancer cells secrete a cable that can reach out and actively grab other cells. Once the cable reaches another cell, it pulls it in forming a larger tumor.

 “There’s nothing but tumorigenic cells in the bridge (between cells),” Soll said in a story in SciCasts, “and that’s the discovery. The tumorigenic cells know what they’re doing. They make tumors.”

They published their work in the American Journal of Cancer Research, and in a press release they suggested the results could provide an alternative to the theory that cancer stem cells are the engine of tumor growth.  I would guess that before too long, someone will find a way to merge the two theories into one, more cohesive story of how cancer grows.

 

3-D home creates stem cells quicker. Using a 3-D gel to grow the cells, a Swiss team reprogrammed skin cells into iPS-type stem cells in half the time that it takes in a flat petri dish. Since these induced Pluripotent Stem cells have tremendous value now in research and potentially in the future treating of patients, this major improvement in a process that has been notoriously slow and inefficient is great news.

The senior researcher Matthias Lutoff from Polytechnique Federale explained that the 3-D environment gave the cells a home closer to the environment where they would grow in someone’s body. In an article in Healthline, he described the common method used today:

 “What we currently have available is this two dimensional plastic surface that many, many stem cells really don’t like at all.”

At CIRM our goal is to get this research done as quickly as possible and to find ways to scale up any therapy so that it becomes practical to make it available to all patients who need it. Healthline quoted our CIRM scientist colleague Kevin Whittlesey on how the work would be a boon for stem cells scientists with its ability to shave months off the process of creating iPS cells.

 

Help for recent spinal cord injury.  A team at Case Western Reserve University in Cleveland used the offspring of stem cells that they are calling multi-potent adult progenitor cells (MAPCs) to modulate the immune response after spinal cord injury. They wanted to preserve some of the role of the immune system in clearing debris after an injury but prevent any overly rambunctious activity that would result in additional damage to healthy tissue and scarring.

a6353-spinalcord

They published their work in Scientific Reports and at the web portal MD the senior researcher Jerry Silver described the project as targeting a specific immune cell, the macrophage, in the early days following stroke in mice:

 

 “These were kinder, gentler macrophages. They do the job, but they pick and choose what they consume. The end result is spared tissue.”

The team injected the MAPCs into the mice one day after injury. Those cells were observed to go mostly to the spleen, which is know to be a reservoir for macrophages, and from their the MAPCs seemed to modulate the immune response.

 “There was this remarkable neuroprotection with the friendlier macrophages,” Silver explained. “The spinal cord was just bigger, healthier, with much less tissue damage.”

 

Rundown on all the mini-organs.  Regular readers of The Stem Cellar know researchers have made tremendous strides toward growing replacement organs from stem cells. You also know that with a few exceptions, like bladders and the esophagus, these are not ready for transplant into people.

Live Science web site does a fun rundown of progress with 11 different organs. They hit the more advanced esophagus and cover the early work on the reproductive tract, with items on fallopian tubes, vaginas and the penis. But most of the piece covers the early stage research that results in mini-organs, or as some have dubbed them, organoids. The author includes brain, heart, kidney, lung, stomach and liver. They also throw it the recent full ear grown on a scaffold.

Each short item comes with a photograph, mostly beautiful fluorescent microscopic images of cells forming the complex structures that become rudimentary organs.

3D printed human ear.

3D printed human ear.

Mini-stomachs.

Mini-stomachs.

This past summer we wrote about an article on work at the University of Wisconsin on the many hurdles that have to be leapt to get actual replacement organs. Progress is happening faster that most of us expected, but we still have a quite a way to go.

Four Challenges to Making the Best Stem Cell Models for Brain Diseases

/ Karen Ring / Leave a comment

Neurological diseases are complicated. A single genetic mutation causes some, while multiple genetic and environmental factors cause others. Also, within a single neurological disease, patients can experience varying symptoms and degrees of disease severity.

And you can’t just open up the brain and poke around to see what’s causing the problem in living patients. It’s also hard to predict when someone is going to get sick until it’s already too late.

To combat these obstacles, scientists are creating clinically relevant human stem cells in the lab to capture the development of brain diseases and the differences in their severity. However, how to generate the best and most useful stem cell “models” of disease is a pressing question facing the field.

Current state of stem cell models for brain diseases

Cold Spring Harbor Lab, Hillside Campus, Location: Cold Spring Harbor, New York, Architect: Centerbrook Architects

Cold Spring Harbor Lab, Hillside Campus, Location: Cold Spring Harbor, New York, Architect: Centerbrook Architects

A group of expert stem cell scientists met earlier this year at Cold Spring Harbor in New York to discuss the current state and challenges facing the development of stem cell-based models for neurological diseases. The meeting highlighted case studies of recent advances in using patient-specific human induced pluripotent stem cells (iPS cells) to model a breadth of neurological and psychiatric diseases causes and patient symptoms aren’t fully represented in existing human cell models and mouse models.

The point of the meeting was to identify what stem cell models have been developed thus far, how successful or lacking they are, and what needs to be improved to generate models that truly mimic human brain diseases. For a full summary of what was discussed, you can read a Meeting Report about the conference in Stem Cell Reports.

What needs to be done

After reading the report, it was clear that scientists need to address four major issues before the field of patient-specific stem cell modeling for brain disorders can advance to therapeutic and clinical applications.

1. Define the different states of brain cells: The authors of the report emphasized that there needs to be a consensus on defining different cell states in the brain. For instance, in this blog we frequently refer to pluripotent stem cells and neural (brain) stem cells as a single type of cell. But in reality, both pluripotent and brain stem cells have different states, which are reflected by their ability to turn into different types of cells and activate a different set of genes. The question the authors raised was what starting cell types should be used to model specific brain disorders and how do we make them from iPS cells in a reproducible and efficient fashion?

2. Make stem cell models more complex: The second point was that iPS cell-based models need to get with the times. Just like how most action-packed or animated movies come in 3D IMAX, stem cell models also need to go 3D. The brain is comprised of an integrated network of neurons and glial support cells, and this complex environment can’t be replicated on the flat surface of a petri dish.

Advances in generating organoids (which are mini organs made from iPS cells that develop similar structures and cell types to the actual organ) look promising for modeling brain disease, but the authors admit that it’s far from a perfect science. Currently, organoids are most useful for modeling brain development and diseases like microencephaly, which occurs in infants and is caused by abnormal brain development before or after birth. For more complex neurological diseases, organoid technology hasn’t progressed to the point of providing consistent or accurate modeling.

The authors concluded:

“A next step for human iPS cell-based models of brain disorders will be building neural complexity in vitro, incorporating cell types and 3D organization to achieve network- and circuit-level structures. As the level of cellular complexity increases, new dimensions of modeling will emerge, and modeling neurological diseases that have a more complex etiology will be accessible.”

3. Address current issues in stem cell modeling: The third issue mentioned was that of human mosaicism. If you think that all the cells in your body have the same genetic blue print, then you’re wrong. The authors pointed out that as many as 30% of your skin cells have differences in their DNA structure or DNA sequences. Remember that iPS cell lines are derived from a single patient skin or other cell, so the problem is that studies might need to develop multiple iPS cell lines to truly model the disease.

Additionally, some brain diseases are caused by epigenetic factors, which modify the structure of your DNA rather than the genetic sequence itself. These changes can turn genes on and off, and they are unfortunately hard to reproduce accurately when reprogramming iPS cells from patient adult cells.

4. Improve stem cell models for drug discovery: Lastly, the authors addressed the use of iPS cell-based modeling for drug discovery. Currently, different strategies are being employed by academia and industry, both with their pros and cons.

Industry is pursuing high throughput screening of large drug libraries against known disease targets using industry standard stem cell lines. In contrast, academics are pursuing candidate drug screening on a much smaller scale but using more relevant, patient specific stem cell models.

The authors point out that, “a major goal in the still nascent human stem cell field is to utilize improved cell-based assays in the service of small-molecule therapeutics discovery and virtual early-phase clinical trials.”

While in the past, the paths that academia and industry have taken to reach this goal were different, the authors predict a convergence between the paths:

“Now, research strategies are converging, and both types of researchers are moving toward human iPS cell-based screening platforms, drifting toward a hybrid model… New collaborations between academic and pharma researchers promise a future of parallel screening for both targets and phenotypes.”

Conclusions and Looking to the Future

This meeting successfully described the current landscape of iPS cell-based disease modeling for brain disorders and laid out a roadmap for advancing these stem cell models to a stage where they are more effective for understanding the mechanisms behind disease and for therapeutic screening.

I agree with the authors conclusion that:

“Moving forward, a critical application of human iPS cell-based studies will be in providing a platform for defining the cellular, molecular, and genetic mechanisms of disease risk, which will be an essential first step toward target discovery.”

My favorite points in the report were about the need for more collaboration between academia and industry and also the push for reproducibility of these iPS cell models. Ultimately, the goal is to understand what causes neurological disease, and what drugs or stem cell therapies can be used to cure them. While iPS cell models for brain diseases still have a way to go before being more clinically relevant, they will surely play a prominent role in attaining this goal.

Meeting Attendees

Meeting Attendees

CIRM Scholar Spotlight: Berkeley’s Maroof Adil on stem cell transplants for Parkinson’s disease

/ Karen Ring / Leave a comment
Maroof Adil, CIRM Scholar

Maroof Adil, CIRM Scholar

Stem cell therapy has a lot of potential for Parkinson’s patients and the scientists that study it. One of our very own CIRM scholars, Maroof Adil, is making it his mission to develop stem cell based therapies to treat brain degenerating diseases like Parkinson’s.

Maroof got his undergraduate degrees from MIT in both Chemical Engineering and Biology, and a PhD in Chemical Engineering from the University of Minnesota. As a graduate student, he dived into the world of cancer research and explored ways of delivering cancer-killing genes specifically to cancer cells in the body while leaving healthy tissues in the body unharmed.

While he enjoyed his time spent on cancer research, he realized his main interest was to apply his skills in chemical engineering and materials science to understand biological problems. This brought him to his current position as a postdoc at UC Berkeley in the Schaffer lab.

Maroof is doing some pretty cutting edge research to develop 3D biomaterials that will vastly improve the transplantation and survival of stem cell derived neurons (nerve cells) in the brain. Check out our exclusive interview with this talented scientist below!

Q: What are you working on and why?

MA: I have always been excited about finding engineering solutions to medically relevant problems. I decided to do a postdoc at UC Berkeley in David Schaffer’s lab because I wanted to combine chemical and materials engineering skills from my graduate research with stem cell technologies to solve biological problems. One of the exciting parts of Dave’s lab, and a reason why I joined, is that he is working on translational stem cell-based regenerative therapies for central nervous system diseases such as Parkinson’s and Huntington’s.

My current research is motivated by the need to find better therapies for these neurodegenerative diseases. While stem cell-based regenerative medicine is an up-and-coming field, there are still a lot of challenges that need to be addressed before stem cells can be successfully used in the clinic. There are three main challenges that are most relevant to my research. First, we need to improve the efficiency of stem cell differentiation, i.e. how well we can convert these stem cells to the mature, functional neurons that we need to treat neurodegenerative diseases. Second, after implanting these cells into the body, we need to increase their survival efficiency. This is because one of the main issues with stem cell-based transplants right now is that after implantation, most of these cells die. Given these first two challenges, we need to generate a lot of cells in order to effectively treat degenerative diseases. The third challenge is to make good quality, functional, transplantable cells in a large-scale fashion.

So given my chemical and materials engineering background, I wanted to see if we could use biologically inspired materials (biomaterials) to address some of these issues with stem cell differentiation and transplantation. In brief, we are developing functionalized biomaterials, differentiating stem cells within these biomaterials into neurons, characterizing the quality of these neurons, and testing the function of these stem cell-derived neurons in animal models of disease.

A major focus of our lab is to develop 3D biomaterials to increase the efficiency of large-scale production of clinical-grade stem cells [and the mature cells that are derived from them]. Our preliminary results suggest that we can get higher numbers of better quality neurons when we differentiate and grow them in 3D biomaterials compared to when they are traditionally grown on a flat, 2D tissue culture surface. Presently, I’m trying to verify that our 3D method works in the lab. If it does, this technology could help us save a lot of time and resources in generating the type of cells we need for effective cell replacement therapies.

Stem cells growing as clusters in 3D[1]Neurons generated in 3D platforms 1[1]

Stem cell derived neurons grown in 3D cultures (left) and generated on 3D biomaterials (right). Images courtesy of Maroof Adil.

Q: Your research sounds fascinating but complicated. How are you doing it?

MA: It’s certainly a multidisciplinary project, and constantly requires us to draw ideas from diverse fields including polymer chemistry, developmental biology and chemical engineering. I am very grateful to be part of a resourceful lab, to my mentors, and to have amazing, motivated people working with me. UC Berkeley provides a highly collaborative work environment. So for some of the follow-up work that further characterizes the quality of these stem cells and their mature cell derivatives, we are collaborating with other labs at UC Berkeley and at UCSF.

Q: Are you interested in applying this work to other brain diseases?

MA: Certainly. Although we are primarily working on generating stem cell-derived dopaminergic neurons, which are the major cell type that die in Parkinson’s patients, I’m also interested in applying similar biomaterials to derive other types of neurons, for instance medium spiny neurons for Huntington’s disease.

The advantage of some of the materials we are working with is their modular nature. That is, we can tune their properties so that they are useful for other applications.

Q: In your opinion what is the future of stem cells in your field? Will they bring cures?

MA: I am very hopeful given what I’m seeing right now in the scientific literature, and in clinical trials for stem cell-based therapies in general. Right now, there are several trials that are testing the benefit and safety of stem cell-based transplants in different diseases. However, right now there are no clinical trials applying stem cell-derived neurons to treat brain diseases. But I think there’s certainly a lot of promise. There are challenges that we need to address in this field, and some of these I outlined earlier. Researchers are working on finding solutions to these problems, and I think that if we find them, the chances of successfully finding cures will be higher.

Q: Tell us about your experience as a CIRM Scholar.

MA: I started as a CIRM scholar in 2014. It was really great to have a source of funding that lined up with what I was interested in, which was doing translational work in regenerative medicine.

I first began working with stem cells when I started my postdoc career, but I didn’t really have a background in this area. So being new to the stem cell field, I felt that CIRM provided the support structure that I needed. And I’m not just referring to funding. CIRM brings scientists with different scientific backgrounds together in one place, where we can learn from one another, and initiate fruitful collaborations. Being a CIRM scholar makes me feel like I’m part of a bigger community, with other scientists conducting very different, but related stem cell research.

Also, I am a big fan of the CIRM blog. I am able to learn about patients and about other researcher’s backgrounds. It helps you realize that patients and researchers are part of the same field. And I like that concept of bringing the field closer: patients towards researchers and researchers towards patients. I think that is useful to boost motivation for researchers, and to give patients a better idea of what we do.

Through CIRM, we’ve had a chance to go out into the local community and present some of our research. For example, the past two years I’ve talked to local high school students during Stem Cell Awareness Week, and that was a really great experience.  I’ve presented to other professionals before, but never to those as young as high school students.  To me, it was quite exciting to realize that these kids are very much interested in the type of work we are doing, and to feel like I was able to influence them to potentially pursue science as a career.

Q: What are your career goals?

MA: I definitely want to stay in science and solve medically relevant problems. It could be nice to be faculty at a research university and in a position to pursue my own independent ideas at the interface of biomaterials and stem cell based therapies. An industry position working towards regenerative medicine or other biologically relevant applications is also an exciting possibility. At this point, being in science is my priority.

Q: What’s your favorite thing about being a scientist?

MA: The excitement you get when your experiments work out, and the joy of making new discoveries. I also like the thrill of designing experiments that may advance the field, and the feeling that what you’re doing day-to-day is contributing to a body of knowledge that others may find useful. I find it especially rewarding to be a scientist in the medical field, working on translational projects closely related to finding cures for diseases.