Mesenchymal Stem Cell-Based Therapy for Type 1 Diabetes

Currently, it’s estimated that nearly 1.5 million Americans are living with type 1 diabetes (T1D), a number that is expected to increase to over 2 million by the year 2040^[1].  In the U.S. alone, healthcare costs and lost wages directly related to T1D currently exceed $16 billion per year.  

While the most common treatment for T1D continues to be regular injections of insulin and is effective in improving hyperglycemia, the treatment has proven ineffective in removing autoimmunity and regenerating lost islets. Additionally, islet transplantation, a recent and experimental treatment option for T1D, has demonstrated its own set of issues, primarily poor immunosuppression and a limited supply of human islets.

The rapid progression and recent advances in stem cell therapy, including mesenchymal stem cell (MSC) therapy, have created interest in using stem cells to help manage the symptoms of T1D. In this review, Hai Wu reviewed the properties of MSCs and highlighted the progress of using MSCs in the potential treatment of T1D.

Diabetes clinics have demonstrated progress using depleting antibodies as a way to treat T1D, but continue to find remission to typically last for only a short period of time. Additionally, treatment with these antibodies has shown not to discriminate between different types of T cells, meaning even T cells involved in maintaining normal immune function are depleted; this phenomenon has been shown to contribute to other serious health complications.

In addition to the immunomodulatory effects demonstrated by MSCs, they have also shown the ability to recruit and increase the immunosuppressive cells of host immunity. Recent results from clinical trials have shown that just a single treatment with MSCs provided a lasting reversal of autoimmunity and improved glycemic control in subjects with T1D. 

While these results demonstrate the potential of MSCs for a wide range of autoimmune diseases, Wu points out that the small sample size of these studies necessitates further clinical trials before considering approval for use in clinical applications.

Studies of human islets and human islet transplantation have been limited because of a shortage of pancreas donors. Although unable to be definitively demonstrated, and considering their ability to differentiate into other cell types, there is a hypothesis that MSCs can transdifferentiate to insulin-producing cells. While not yet fully understood, this hypothesis is further supported by the observation of crosstalk between MSCs and the pancreas in diabetic animals.

Other in vivo studies examining this relationship has produced mixed results.  For example, Chen et al. (2004) were unsuccessful in attempts to transdifferentiate MSCs into insulin-producing cells in vitro. On the other hand, several studies, including those by Timper et al. (2006) and Chao et al. (2008) demonstrate the formation of islet-like clusters from in vitro cultured MSCs and the possibility of using MSCs as a source of human islets in vitro.

Despite these promising findings, the author highlights that most of these studies failed to generate sufficient amounts of islets required for human transplantation and long-term stability.  However, Wu notes recent advances in tissue engineering, including biocompatible scaffolds, might better support in vitro generation of islets from MSCs.

The author concludes that MSCs can be isolated from multiple tissues, are easily expanded and genetically modified in vitro, and are well-tolerated in both animal and human studies – making them a good candidate for future cell therapy.  On the other hand, stem cell therapy alone might not be enough to reverse the autoimmunity of T1D, and co-administration of immunosuppressive drugs may be necessary to prevent autoimmunity. 

MSCs have shown great promise in the field of regenerative medicine. While stem cells used as a potential treatment for T1D appear generally safe, the author calls for future in-depth mechanistic studies to overcome the identified scientific and manufacturing hurdles and to better learn how cell therapy can be used to treat – and eventually cure – T1D.

Source: “Mesenchymal stem cell-based therapy for type 1 diabetes – PubMed.” https://pubmed.ncbi.nlm.nih.gov/24641956/.

^[1] “Type 1 Diabetes Facts – JDRF.” https://www.jdrf.org/t1d-resources/about/facts/. Accessed 2 Nov. 2022.