Mesenchymal Stem Cell Transplantation for Ischemic Diseases: Mechanisms and Challenges.

Ischemic diseases are conditions associated with the restriction or blockage of blood supply to specific tissues. These conditions can cause moderate to severe complications in patients, and can lead to permanent disabilities. Since they are blood vessel-related diseases, ischemic diseases are usually treated with endothelial cells or endothelial progenitor cells that can regenerate new blood vessels. However, in recent years, mesenchymal stem cells (MSCs) have shown potent bioeffects on angiogenesis, thus playing a role in blood regeneration. Indeed, MSCs can trigger angiogenesis at ischemic sites by several mechanisms related to their trans-differentiation potential. These mechanisms include inhibition of apoptosis, stimulation of angiogenesis via angiogenic growth factors, and regulation of immune responses, as well as regulation of scarring to suppress blood vessel regeneration when needed. However, preclinical and clinical trials of MSC transplantation in ischemic diseases have shown some limitations in terms of treatment efficacy. Such studies have emphasized the current challenges of MSC-based therapies. Treatment efficacy could be enhanced if the limitations were better understood and potentially resolved. This review will summarize some of the strategies by which MSCs have been utilized for ischemic disease treatment, and will highlight some challenges of those applications as well as suggesting some strategies to improve treatment efficacy.

Transcriptional Factors of Thermogenic Adipocyte Development and Generation of Brown and Beige Adipocytes From Stem Cells.

Brown and beige adipocytes have been widely known for their potential to dissipate excessive energy into heat form, resulting in an alleviation of obesity and other overweight-related conditions. This review highlights the origins, characteristics, and functions of the various kinds of adipocytes, as well as their anatomic distribution inside the human body. This review mainly focuses on various essential transcriptional factors such as PRDM16, FGF21, PPARα, PPARγ and PGC-1α, which exert their effects on the development and activation of thermogenic adipocytes via important pathways such as JAK-STAT, cAMP-PKA and PI3K-AKT signaling pathways. Additionally, this review will underline promising strategies to generate an unexhausted source of thermogenic adipocytes differentiated from human stem cells. These exogenous thermogenic adipocytes offer therapeutic potential for improvement of metabolic disorders via application as single cell or whole tissue transplantation. Graphical abstract Caption is required. Please provide.