The idea of stem cell therapy for diabetes is both exciting and in a way practical. By that I mean that there’s a good common sense foundation here.
The idea of stem cell therapy for diabetes
What do I mean?
If medical researchers can replace lost beta cells in the pancreas using stem cell-produced beta cells, diabetes might be effectively treated or even cured in some cases.
It’s possible that the transplanted beta cells don’t even need to be in the pancreas itself.
But you’ve got to have persistent cells both sensing blood sugar levels and making the right amount of insulin over time.
A PubMed search found 356 papers with title words stem cells and diabetes. There’s understandably a great deal of interest in this kind of research. Unfortunately, it’s such early days that there aren’t any relevant trial meta analyses. Here’s a SCOPUS search sorted by citations.
A review this year in the journal Cells includes a very helpful timeline (above) of how this field has been evolving and future directions.
You can see a video I’ve done about this post which gives a nice concise overview of the key topics I cover here. If you like that video or others in our stem cell series please subscribe to our stem cell YouTube channel.
Clinical trials, possible IPO
It’s still early days in terms of human studies, but some trials provide at least hope here for the future.
ViaCyte is doing clinic trial work right now on implantable capsules that may be placed under the skin in the back. These devices contain pancreatic progenitor cells at the time of implantation. Once inside the body, the cells mature and a subpopulation becomes beta cells that control blood sugar in animal studies.
I’m excited to see how that work progresses and how trials by other teams turn out. Some are trying to use just populations of already differentiated beta cells made from stem cells.
It’ll be interesting to see how the different approaches compare as trial data accumulates.
There currently are 230 clinical trial listings for stem cells for diabetes including the search phrase “stem cells.” This kind of Clinicaltrials.gov search can bring up false positives, but in a quick scan through some of the listings there are quite a few actual interventional trials. At the same time this sort of search can miss trials as well.
As I’ve expected for a few years, it’s looking increasingly likely that we’ll see a Viacyte IPO. I thought it’d be an IPO or an acquisition by another larger firm. Viacyte also has a collaboration with CRISPR therapeutics for gene-editing to make cells more suited for transplantation.
In another exciting development, Vertex, which acquired Semma a couple years back, is launching its first diabetes trial with iPS cell-derived islet cells.
Recent stem cells for diabetes papers of note
- Preprint: Functional, metabolic and transcriptional maturation of stem cell derived beta cells, from Timo Otonkoski group.
- Glucose Response by Stem Cell-Derived beta Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis. Davis JC, Alves TC, Helman A, Chen JC, Kenty JH, Cardone RL, Liu DR, Kibbey RG, Melton DA.Cell Rep. 2020 May 12;31(6):107623. doi: 10.1016/j.celrep.2020.107623.PMID: 32402282
- Inducible Pluripotent Stem Cells as a Potential Cure for Diabetes. Verhoeff K, Henschke SJ, Marfil-Garza BA, Dadheech N, Shapiro AMJ.Cells. 2021 Jan30;10(2):278. doi: 10.3390/cells10020278.
- Identification of a LIF-Responsive, Replication-Competent Subpopulation of Human beta Cells. Rosado-Olivieri EA, Aigha II, Kenty JH, Melton DA. Cell Metab. 2020 Feb 4;31(2):327-338.e6. doi: 10.1016/j.cmet.2019.12.009. Epub 2020 Jan 9.
Some of the complex challenges
Trying to treat type-I diabetes faces challenges. Transplanted beta cells derived from some other person might be wiped out by the immune system either right away or eventually over time. In the latter scenario this might require additional fresh treatments on an ongoing basis over the lifetime of the patient. Encapsulated devices are ideally suited for that kind of situation as they can be popped out and replaced with new capsules. These devices also lower risks of cells within the device escaping and potentially causing issues.
Still, there are specific challenges for the implanted encapsulated devices containing pancreatic cells. They must form a vascular connection to the rest of the body to most effectively sense blood sugar. That feature would aid in the effectiveness of insulin secretion too. This sensing-secreting kind of mechanism requires an exquisite balance. Hypoglycemia is a real risk if the device isn’t “tuned” right.
At the same time, forming a vascular connection means the potential for the patient’s immune cells to attack the cells in the device. Most studies are focusing on allogeneic cells, meaning cells from someone else. For this reason there’s real potential for immune rejection. This also raises the issue of possibly using immunosuppressants.
Another factor is that for a robust vascular connection the devices probably need to be at least partially “open” in the sense of allowing for blood vessel entry. This could also allow destructive immune cells inside.
Even with using a patient’s own cells, it’s possible that in the diabetic context that the patient’s immune system could attack the transplanted cells.
Using the patient’s own cells such as via induced pluripotent stem cells or iPS cells could eliminate some of the possible immune issues. It’s good that different groups and biotechs are pursuing both autologous and allogeneic pathways.
Type-II diabetes too?
Millions of people have type-II diabetes. There has naturally been discussion of the idea of using stem cell therapy here as well. However, the mechanisms of type-II diabetes are fairly different. A beta cell-containing medical implant might not work that well in this case.
Others have proposed that stem cells may help type-II diabetes indirectly. For instance, they theorize that infusions of stem cells might alter hormones, inflammation, or something else in some beneficial way.
I’m more skeptical of this kind of idea.
The notion of using MSCs or bone marrow cells to treat diabetes more generally also seems like a long shot to me. However, even so this approach is sold by stem cell clinics across the U.S. and the world.
Future perspectives
Overall, treating type-I diabetes with stem cell or cellular therapy-based approaches seems extremely promising.
One way or another I believe we’re going to get there to a safe, effective treatment.
It’s just likely to take longer than one would have hoped. Already, after following this area for more than a decade things have turned out to be more complicated than I might have hoped back ten or more years ago.
In another 10 years or less I predict we’ll see an FDA-approved cellular therapy-based treatment for type-I diabetes.
References
- Clinicaltrials.gov search on June 8, 2021 for stem cell therapy for diabetes.
- June 8, 2021 PubMed search with title words stem cells and diabetes.
- Inducible Pluripotent Stem Cells as a Potential Cure for Diabetes, Verhoeff, et al. Cells, 2021.
- Endpoints on ViaCyte, June 9,2021.
When I get back from treatment I will tell the world if it worked or didn’t work.thank you for listening
I am going down to Tijuana for stem cell treatment of my diabetes, my kidneys and my nervous system. My friend is also coming along to get stem cell treatment for his ataxia .I hope it all works I will post how everything went when I return
Hi Ralph,
I hope you might reconsider and not go. It sounds risky to me and not likely to do anything helpful. If you are comfortable sharing, what kind of stem cells are you going to get? What evidence is the Tijuana place showing you that gives you confidence this might be helpful.
Good luck to you. Paul