Advances and complications of regenerative medicine in diabetes therapy

Abstract

The rapid development of technologies in regenerative medicine indicates clearly that their common application is not a matter of if, but of when. However, the regeneration of beta-cells for diabetes patients remains a complex challenge due to the plurality of related problems. Indeed, the generation of beta-cells masses expressing marker genes is only a first step, with maintaining permanent insulin secretion, their protection from the immune system and avoiding pathological modifications in the genome being the necessary next developments. The prospects of regenerative medicine in diabetes therapy were promoted by the emergence of promising results with embryonic stem cells (ESCs). Their pluripotency and proliferation in an undifferentiated state during culture have ensured the success of ESCs in regenerative medicine. The discovery of induced pluripotent stem cells (iPSCs) derived from the patients’ own mesenchymal cells has provided further hope for diabetes treatment. Nonetheless, the use of stem cells has significant limitations related to the pluripotent stage, such as the risk of development of teratomas. Thus, the direct conversion of mature cells into beta-cells could address this issue. Recent studies have shown the possibility of such transdifferentiation and have set trends for regeneration medicine, directed at minimizing genome modifications and invasive procedures. In this review, we will discuss the published results of beta-cell regeneration and the advantages and disadvantages illustrated by these experiments.

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

“…Immunotherapies and cell replacement, which include islet transplantation and stem cell differentiation into β-cells, are the primary treatment strategies for T1DM [ 126 , 127 ]. The simultaneous restorative and immunomodulatory properties of EVs aligned with new hypotheses regarding the nature of T1DM could make them a favorable treatment option.…”

Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair

“…However, ESC application is associated with social and moral issues regarding embryonal tissue decomposition [ 35 ]. Moreover, the risk of tumor formation is another problem that cannot be overlooked [ 39 ].…”

Extracellular Vesicle Therapy for Type 1 Diabetes

“…The main treatment strategies for T1D are immunotherapies (1) and cell replacement, including islet transplantation and stem cell differentiation into b-cells as a cell replacement method (7). As a new opportunity, EVs, with their therapeutic properties, had emerged (21,42).…”

“…Surgical islet transplantation and/or whole pancreas transplantation are the only current treatments for restoring the b-cells (7). Islet transplantation faces a limited source of islet donors and immune destruction after transplantation, requiring immunosuppression therapy (8,9).…”

“…Technological shortcomings, the limited translational success of adapting preclinical rodent studies to humans, and the ambiguity of the T1D pathogenesis have been involved in the current limitations of immunotherapies for T1D (5,10,11). Stem cell-based therapies that aim to replace or regenerate destructed b-cell are broadly investigated treatments (7). Although showing promising results, stem cell-derived b-cells need to be protected from immune-mediated destruction.…”