Mesenchymal Stem Cells in Regenerative Medicine and Immunomodulation

Dear Colleagues,

Mesenchymal stem cells (MSCs) represent a heterogeneous population of adult, fibroblast-like, multipotent cells. MSCs have drawn much attention in the field of regenerative medicine over the last decade. Due to their immunomodulatory properties, they are now considered an extraordinary opportunity for multifunctional therapeutic approaches. They have the capacity to differentiate into specific cell types and produce several soluble growth factors and cytokines, as well as possessing supporting properties, all of which enable them to contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, and adipose. MSCs can migrate to sites of inflammation and induce significant immunomodulatory and anti-inflammatory effects through cell-to-cell interactions between MSCs and lymphocytes or through the production of soluble factors. Therefore, the application of MSCs in many disease situations points to future clinical treatments. In addition, hundreds of clinical trials are being run using MSCs for the treatment of several immune-mediated diseases, including GVHD, rheumatoid arthritis (RA), and COVID-19. Manufacturing MSCs for clinical trials is also an important aspect as their differentiation, homing, and immunomodulatory properties may sometimes differ. Since these cells are "immunoprivileged," they may be the first cell type able to be used as an "off-the-shelf" therapeutic product. It has been demonstrated that cultured MSCs have the ability, upon migration, to engraft into healthy as well as injured tissue and can differentiate into several cell types in vivo, which makes MSCs an ideal tool for regenerative therapy in different disease types. The immunomodulatory effects of MSCs during damage repair seem to be crucial for exploring novel immunomodulatory strategies to achieve disease recovery and tissue regeneration. Nevertheless, some observations have raised questions about the limitations for proper use of MSCs considering some critical factors that warn against regular clinical use.

New observations and reviews of MSCs' immunomodulatory properties and potential mechanisms, as well as their effects on immunomodulation-mediated disease therapies and tissue regeneration, will be of invaluable interest to readers for the future development of MSC-based clinical applications.

Dr. Biancamaria Longoni
Dr. Serena Barachini
Dr. Hiroshi Wakao
Guest Editors

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