In their extensive review, entitled “Therapeutic Potential of Wharton’s Jelly Mesenchymal Stem Cells for Diabetes: Achievements and Challenges,” and published in the January 2020 issue of Frontiers in cell and developmental biology, researchers Mohamed Kamal and Dina H Kassem present interesting and compelling arguments for the clinical value of these unique stem cells, along with the challenges they currently face for practical application in the treatment of Diabetes.
Diabetes Mellitus—a progressively worsening disease with complicated medical management
Diabetes mellitus (DM) holds the title as the most prevalent metabolic disease of our time. While numerous studies have been and continue to be designed to improve treatment modalities, DM remains a disease significant affecting the quality of life of those who suffer with it, along with increased mortality.
Currently, biological models of research in DM are focused on studying the insulin-secreting β-cells inside the pancreas. Specifically, understanding the mechanisms for damage to these cells and whether or not the regenerative and reparative processes of stem cell therapies can help.
However, any traditional transplantation of live tissue is risky. Notably, the lack of donor tissue, immune rejection, and the damage that immunosuppressive drugs can further impart present the greatest barriers to treatment used now.
The unique characteristics of mesenchymal stem cells
With regards to stem cell transplant, mesenchymal stem cells (MSCs) derived from umbilical cord blood (UCB-MSCs) appear to circumvent almost all of the concerns discussed above. They offer reparative effects on a wide range of damaged tissue, they’re easily accessible from cord blood (otherwise discarded as medical waste), they appear to escape detection by the recipient’s immune system, and they are readily expanded in the lab.
Wharton’s Jelly—the mucous-like substance that surrounds the vessels contained within the umbilical cord—contains MSCs that are particularly appealing. While only 6% of MSCs can be extracted from cord blood, 100% of the stem cells in Wharton’s Jelly (WJ-MSCs) are available. In addition, WJ-MSCs tend to behave both like adult cells and primitive ones. This is important because they do not pose as many risks as other stem cells do, like the propensity for MSCs to form tumors.
Because it has become a common practice today to bank cord blood at the time of birth, robust amounts of these cells have the potential to be readily available. Add that to the lack of immune response issues, and the authors believe that WJ-MSCs should become the new gold standard for MSC therapies in general.
Clinical application of WJ-MSCs—what is known and what remains to be discovered
MSCs, in general, were first believed to be helpful strictly because they could grow new cells and replace damaged ones. However, it is now understood that they have abilities that go far beyond that.
In particular, WJ-MSCs are clinically helpful for the same reasons as MSCs (and a couple more), but much remains to be understood about their exact mechanism of action. It is this lack of knowledge that prevents their therapeutic application now. The following is a list of their known benefits, along with current knowledge gaps.
- Homing — Cells injected via IV have the ability to travel to an injury site. However, a number of factors influence their ability to do this correctly: how they’re grown in the lab, the patient’s health, and whether their entrapment in other organs (especially within the lungs) cause damage there.
- They can soothe their microenvironment — Once at the site of injury WJ-MSCs calm inflammation there. Scientists also believe they can possibly “reprogram” recipient cells as well. While the micro-reactions that make this possible are understood in a lab setting, it is uncertain from a broad scale exactly how this occurs within injured tissues, as well as the overall long-term effect this has within the body.
- They have a positive effect on immune function — WJ-MSCs express a huge amount of immunosuppressants called cytokines, making them safer for allogenic (unmatched donor-recipient) transplantation. At the site of β-cells, they release macrophages which enhance insulin sensitivity. It is unknown if this effect lasts long-term, however, once the WJ-MSCs mature.
- They have potential for differentiation — This ability to regenerate a wide range of injury is good. The regrowth of β-cells has been demonstrated in rat studies, and WJ-MSCS elicit better outcomes in diabetic rats than MSCs from bone marrow. However, studies have shown that they exert more anti-inflammatory and immunomodulatory effects than regenerative ones.
- They might be a potential tool for gene therapy — Injection of genetically modulated WJ-MSCs had great response over several treatment categories for DM, but remains unclear if this benefit outweighs injection of unmodified WJ-MSCs.
Future applications for the treatment of DM
Of the 980 MSC trials being conducted as of August 2019, 64 were investigating DM, and only 16 were looking into WJ-MSCs specifically. Most of these trials have not reported outcomes yet, but the ones that have have reported greater β-cells function, less insulin requirements, and better metabolic control for patients with both DM type 1 and 2. These studies all demonstrated the use of WJ-MSCs to be safe, with a low incidence of side effects. However, the prime mechanism of action of the WJ-MSCs may be more anti-inflammatory and immunomodulatory than regenerative-based.
As researchers look for ways to apply WJ-MSC treatment, several challenges remain. These include problems and limitations with industrial manufacturing like:
- sensitivity to environmental conditions of the lab where they are expanded
- genetic and viral testing
- cryopreservation of cell lines
- establishing dosage
- universal banking practices
- trademarking live tissue
As studies continue to be designed to learn about WJ_MSCs, the authors hope that further investigation will answer a few key questions. Will mature cells derived from WJ-MSCs carry with them their immuno-privileged status? Is it better to inject immature cells or should they be differentiated within the lab to produce β-cells first? What are the long term effects of stem cell therapy in general?
Much is left to discover in this genre of research. One recommendation remains clear above all others. The benefits and unique expression of WJ-MSCs make it a top contender for future stem cell therapy. And, those with a family history of DM would be particularly well-advised to bank both cord blood and tissue as a routine practice.