Stem Cell Therapy in Limb Ischemia: State-of-Art, Perspective, and Possible Impacts of Endometrial-Derived Stem Cells

Abstract

As an evidence-based performance, the rising incidence of various ischemic disorders has been observed across many nations. As a result, there is a growing need for the development of more effective regenerative approaches that could serve as main therapeutic strategies for the treatment of these diseases. From a cellular perspective, promoted complex inflammatory mechanisms, after inhibition of organ blood flow, can lead to cell death in all tissue types. In this case, using the stem cell technology provides a safe and regenerative approach for ischemic tissue revascularization and functional cell formation. Limb ischemia (LI) is one of the most frequent ischemic disease types and has been shown to have a promising regenerative response through stem cell therapy based on several clinical trials. Bone marrow-derived mononuclear cells (BM-MNCs), peripheral blood CD34-positive mononuclear cells (CD34+ PB-MNCs), mesenchymal stem cells (MSCs), and endothelial stem/progenitor cells (ESPCs) are the main, well-examined stem cell types in these studies. Additionally, our investigations reveal that endometrial tissue can be considered a suitable candidate for isolating new safe, effective, and feasible multipotent stem cells for limb regeneration. In addition to other teams’ results, our in-depth studies on endometrial-derived stem cells (EnSCs) have shown that these cells have translational potential for limb ischemia treatment. The EnSCs are able to generate diverse types of cells which are essential for limb reconstruction, including endothelial cells, smooth muscle cells, muscle cells, and even peripheral nervous system populations. Hence, the main object of this review is to present stem cell technology and evaluate its method of regeneration in ischemic limb tissue.

Mesenchymal Stromal Cells Overexpressing Farnesoid X Receptor Exert Cardioprotective Effects Against Acute Ischemic Heart Injury by Binding Endogenous Bile Acids

“…Earlier studies demonstrated that Nqo-1 counteracts intracellular ROS generation, thus attenuating DNA damage and improving cell survivability. [26,72] Our experimental results confirm for the first time that bile acid-FXR axis activation significantly improves the antiapoptotic effect of ADSC by promoting Nqo-1 expression, thus increasing the quantity of transplanted MSC.…”

“…[ 70,71 ] However, as one of the key features in the myocardial ischemic microenvironment, excessive oxidative stress is directly harmful to ADSC survival. [ 26 ] Inconsistent with the in vivo results, cellular experiments failed to confirm that FXR overexpression promoted ADSC survival under oxidative stress. However, in the presence of bile acids, ADSC‐FXR exhibited a stronger antioxidative damage ability.…”

“…Compared with the cell culture environment in vitro, the myocardial ischemic microenvironment in vivo is more complicated. [26,45] There is increasing evidence that multiple metabolic disorders occur in the progression of myocardial ischemia, such as glucose, branched chain amino acids, and lipid metabolism disorders, and those metabolic alterations further influence disease progression. [46][47][48][49][50] It has been reported that as one of the central tenets of microbehost crosstalk, bile acids have the potential to influence host cardiometabolic health.…”

“…Increased oxidative stress is one of the key features of acute MI and is directly tied to ADSC apoptosis. [26,27] Previous studies have uncovered the antioxidative role of FXR activation in liver or renal cells. [28][29][30][31] To clarify whether bile acid-FXR signal activation affects oxidative stress, several important antioxidative stress molecules were assessed in ADSC-con/ADSC-FXR treated with vehicle or OCA.…”

Targeting Grancalcin Accelerates Wound Healing by Improving Angiogenesis in Diabetes

“…The bone marrow‐derived cell (BMDC) induces paracrine release of cytokines, exosomes, and growth factors to promote tissue regeneration and wound repair. [ 3 ] The therapeutic effects of BMDCs in diabetes‐related vascular complications, including DFUs, [ 4 ] diabetic nephropathy, [ 5 ] and limb ischemia, [ 6 ] have been reported. Although most of these studies focused on the beneficial BMDC‐induced paracrine factors, several studies have indicated that BMDCs from animals and individuals with diabetes evince a major beneficial‐to‐harmful alteration in their secretome components.…”