Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases

Abstract

Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.

Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review

“…Tian et al (2022) highlighted the research on tissue engineering of blood vessels using AD-MSCs as seed cells and self-assembled nano-polypeptide hydrogel for 3D printing of biological tissues [ 116 ]. These things considered, other studies have shown that MSCs can promote blood vessel formation and improve tissue perfusion in conditions such as myocardial infarction (MI) and hind limb ischemia [ 117 , 118 , 119 ]. In a study, MSCs were investigated in a murine model of hind limb ischemia.…”

The regulatory effect of growth differentiation factor 11 on different cells

“…For instance, GDF11 plays a therapeutic role in cardiovascular system diseases and nervous system diseases via the regulation of MSCs and neural stem cells (NSCs). MSCs can be used for treating ischemic diseases to promote angiogenesis has been extensively carried out (Figure 2C) (57)(58)(59). However, the regulatory function of GDF11 on NSCs are controversial.…”

Current Progress in Treating Systemic Lupus Erythematosus Using Exosomes/MicroRNAs

“…Further studies are needed to decode the complexity of exosome components to better understand the safety of their combined effects on target tissues. Bioengineering efforts are also needed to achieve the amplification and safe production of compositionally homogeneous exosomes containing specific miRNAs or inhibitors 105 of miRNAs 106 . The optimal dose and frequency of exosome administration should also be determined to maximize efficiency 107 .…”