Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities

Abstract

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.

Keywords: Cardiovascular diseases; Mesenchymal stem cells (MSCs): regenerative therapies; Neurological disorders; Reproductive disorders, endocrine-related diseases; Respiratory diseases; Skin burns.

Fig. 1

Sources, secretome composition, and therapeutic benefits of MSCs. MSCs can be obtained from several tissues, including the umbilical cord, BM, teeth, and AT. Prominent therapeutic applications of MSCs include neuroprotection, wound healing acceleration, angiogenesis induction, inflammation suppression, and prevention of cell apoptosis. This figure is modified by the corresponding author with permission from reference [44]

Fig. 2

(A) MSCs treat CVD by regulating inflammation, preventing fibrosis, promoting neovascularization, and differentiating into cardiomyocyte-like cells. (B) Approaches to improve the therapeutic impact of MSCs in CVD. To improve the therapeutic effects of MSCs, techniques such as 3D culture, patches containing MSCs, preconditioning with hypoxia or chemicals, gene modification, and viral injections combined with small compounds or shRNA have been employed. This figure is modified from reference [107]

Fig. 3

(A) The primary functions of MSCs in asthma, ARDS, idiopathic pulmonary fibrosis (IPF), and COPD. (B) Characteristics of MSCs in common respiratory inflammatory diseases. This figure is adapted and is freely accessible online from reference [163], Licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0)

Fig. 4

(A) AT, which supports and regulates numerous functions, is regarded as an endocrine organ. (B) T2DM affects AT’s function in lipid and glucose metabolism as well as appetite regulation, rendering autologous AT-MSCs inappropriate for treating metabolic disorders. Healthy donor-derived allogeneic AT-MSCs may therefore represent a more viable alternative. (C) AT-MSCs are effective in treating reproductive disorders owing to their capacity to migrate and establish a microenvironment within the damaged ovary, enhance cell regeneration, and regulate growth hormones. (D) AT-MSCs promote skin healing and regeneration by supporting neovascularization, angiogenesis, anti-apoptosis, inflammation regulation, and immunoregulation. This figure is adapted and is freely accessible online from reference [40], Licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0)