STEM CELLS TREATMENT FOR DIABETIC MELLITUS
Recently, stem cell treatment has to reach positive results in medicine regarding the replacement, repair, and regeneration properties. Of note, 3R therapy utilize stem cells and as an effective implementation to repair, prevent, replace, and treat damaged organs. In fact, stem cell treatment has been used successfully in diabetes, from preclinical to clinical researches. (6) Stem cell transplantation is a great platform for diabetes treatment due to the fact that it can decrease the progression of diabetes and stop the complications of long-term blood glucose associated effect.
THE UMBILICAL CORD MSCS
TREATING DIABETIC MELLITUS
The most favored stem cell type that has been proved in diabetes mellitus therapy have been mesenchymal stem cells (MSCs). These cells have excellent potential and it is practicable to isolate them, there is an abundant source, and ethical problems are minimal. Mesenchymal stem cells are distributed everywhere in the body and can then be extracted from multiple sources, for example, the heart, bone marrow, skin, bodily fluids, and perinatal tissues. Mesenchymal stem cells respond to internal tissue environmental changes such as PH, oxygen, stress by producing immune-modulatory factors known to regenerate injured cells and tissues. (5)
Studies have proven that mesenchymal stem cells can be extracted, expanded, and cryopreserved from both Wharton’s jelly (umbilical cord matrix) and umbilical cord blood. However, advantages to the extract of mesenchymal stem cells from the Wharton’s jelly (WJ) include a higher yield, increased likelihood of successful MSC isolation, a more homogenous stem cell population, and better potential to turn into insulin-producing cells. (5)
MESENCHYMAL STEM CELL TRANSPLANTATION FOR DIABETES MELLITUS
It is known that MSCs play a crucial role in healing damaged tissues. They can differentiate to replace the dead cells as well as secrete stimulant factors to activate surrounding cells in the microenvironment, enhancing the tissue repair process. Therefore, MSCs can be applied to treat tissues impaired by chronic hyperglycemia. For T1DM, MSC transplantation can theoretically increase beta-cell mass via the following effects:
(1) beta cell replacement through in vitro or in vivo differentiation; (2) local microenvironment modification by the production of cytokines, chemokines, and factors to stimulate endogenous regeneration; (3) reduction or prevention of autoimmunity to beta cells. Although several MSC
transplantation studies have clearly shown the outcome of controlled glucose metabolism, there have been observations of decreased insulin resistance as well as enhanced beta-cell function effects. Moreover, the mechanisms of MSC treatment for T2DM still has not been well understood. Some studies have suggested that the immunomodulatory and inflammatory effects of MSCs are what contribute to the resulting reduction of insulin resistance. (6)
STEM CELL TRANSPLANT FOR DIABETES
MECHANISM OF ACTION
Cell replacement It has been proved that mesenchymal stem cell treatment can ameliorate blood glucose levels within the follow-up time from few weeks to several years. However, the mechanism behind this effect is still unclear. One mechanism is the replacement ability of transplanted mesenchymal stem cells derived cells. Mesenchymal stem cells are potentially to turn into insulin-producing cells and have been suggested to work instead of impaired pancreas cells in diabetic animals. Even though mesenchymal stem cells can be induced to produce insulin in the laboratory and in the human body, few mesenchymal stem cells become fully functional pancreas in the human body (only approximately 1.7 – 3% of transplanted cells). In addition, the temporary survival of transfused cells confirms that the replacement potential may not be the only reason for the therapeutic effect of mesenchymal stem cells. Sordi and team. have found the role of mesenchymal stem cells as support cells when they observed neovascular formation and normalized blood glucose levels after transplantation of pancreatic mesenchymal stem cells and islet mass.
Immune regulation: Not only the differentiation ability, but mesenchymal stem cells also have the special ability to regulate immune responses through multiple mechanisms. In the laboratory, the ability to decrease immune system sensitivity of mesenchymal stem cells was discovered in the late 1990s. When stem cells culture with white blood cells, it is found that mesenchymal stem cells are able to change the cell division of multiple types of immune cells. They have the potential to stop white blood cell generation and function. In particular, mesenchymal stem cells are able to modulate the immune system to inhibit inflammation, resulting in reducing insulin resistance in diabetes type 2. Mesenchymal stem cells are capable of reducing autoimmune responses in diabetes type 1. It has been shown that mesenchymal stem cells can secrete much essential substance which modulates and improve the surrounding cells.
UMBILICAL CORD STEM CELLS,
IMMUNE PRIVILEGE PROPERTY
It has been proposed that mesenchymal stem cells do not only have the ability to change into various kinds of adult stem cells but also universal donor cells because of their ability to avoid immune rejection. Furthermore, systemic delivery of mesenchymal stem cells derived from patient cells or other person source or even animal have been reported which can generate non-specific systemic immunosuppression. The transplanted mesenchymal stem cells could survive and differentiate in other person or animal recipients due to their immunotolerance capability. Atoui and team. have shown that the underlying mechanism of immunotolerance capability of mesenchymal stem cells comes from their low immune triggering, immune modulation, and immune suppression. As a result, transplanted mesenchymal stem cells can be tolerated (in part) in the recipients and can produce local pancreatic stem cells to generate, leading to the replacement of impaired cells in the diabetic.
Reference 1.Harvard Health Publishing “Diabetic Type 2” Harvard Medical school 2.Mayo Clinic “Type 2 diabetic “ https://www.mayoclinic.org/diseases-conditions/type-2- diabetes/symptoms-causes/syc-20351193 3.International diabetes foundation “Type 2 diabetes” 4.EMRO Technical Publications Series 32” Guidelines for the prevention, management and care of diabetes mellitus” World Health Organization 5.Alvaro Moreira, Samuel Kahlenberg “Therapeutic Potential of Mesenchymal Stem Cells for Diabetes”, J Mol Endocrinol. 2017 Oct 6.Loan Thi-Tung Dang ,Ngoc Kim Phan,Kiet Dinh Truong, “Mesenchymal stem cells for diabetes mellitus treatment: new advances “ Biomedical Research and therapy
