From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Immunological Considerations

Abstract

Mesenchymal stem cell (MSC)-based therapy for type 1 diabetes mellitus (T1DM) has been the subject matter of many studies over the past few decades. The wide availability, negligible teratogenic risks and differentiation potential of MSCs promise a therapeutic alternative to traditional exogenous insulin injections or pancreatic transplantation. However, conflicting arguments have been reported regarding the immunological profile of MSCs. While some studies support their immune-privileged, immunomodulatory status and successful use in the treatment of several immune-mediated diseases, others maintain that allogeneic MSCs trigger immune responses, especially following differentiation or in vivo transplantation. In this review, the intricate mechanisms by which MSCs exert their immunomodulatory functions and the influencing variables are critically addressed. Furthermore, proposed avenues to enhance these effects, including cytokine pretreatment, coadministration of mTOR inhibitors, the use of Tregs and gene manipulation, are presented. As an alternative, the selection of high-benefit, low-risk donors based on HLA matching, PD-L1 expression and the absence of donor-specific antibodies (DSAs) are also discussed. Finally, the necessity for the transplantation of human MSC (hMSC)-derived insulin-producing cells (IPCs) into humanized mice is highlighted since this strategy may provide further insights into future clinical applications.

Insulin-producing cells from bone marrow stem cells versus injectable insulin for the treatment of rats with type I diabetes

“…Recent studies in laboratory and animal models have shown that mesenchymal stem cells play an effective role in regulating immunity in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and encephalitis [17,18]. Recently, many researchers have become interested in adult stem cells because they can transform into many tissues and there is no moral concern about using them [19,20].…”

Comparison of therapeutic effects of mesenchymal stem cells from umbilical cord and bone marrow in the treatment of type 1 diabetes

“…The underlying mechanism is mainly associated with modulating autoimmune responses against islets. In addition to suppressing pathogenic CD8 + T cells, T helper 1 (Th1) cells and T helper 17 (Th17) cells [ 9 , 10 ], MSCs can also promote regulatory T cells (Tregs) through paracrine effects, direct cell receptor interactions or mitochondrial transfer [ 11 , 12 ]. Because islets are highly vascularized mini-organs, the promotion of angiogenesis by MSCs in islets is another potential mechanism in T1D [ 13 , 14 ].…”

Mesenchymal Stem Cells‐Derived Extracellular Vesicles in Orthopedic Diseases: Recent Advances and Therapeutic Potential

“…MSCs can also be induced to differentiate into insulin‐secreting cells and adjust the state of the body's immune system, which is expected to have potential in the treatment of endocrine diseases such as diabetes. [ 26 ] MSCs have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes, and have strong effects on the repair and regeneration of cartilage and bone defects [ 27 ] ( Figure ).…”