Preconditioning and Stem Cell Survival

Abstract

The harsh ischemic and cytokine-rich microenvironment in the infarcted myocardium, infiltrated by the inflammatory and immune cells, offers a significant challenge to the transplanted donor stem cells. Massive cell death occurs during transplantation as well as following engraftment which significantly lowers the effectiveness of the heart cell therapy. Various approaches have been adopted to overcome this problem nevertheless with multiple limitations with each of these current approaches. Cellular preconditioning and reprogramming by physical, chemical, genetic, and pharmacological manipulation of the cells has shown promise and "prime" the cells to the "state of readiness" to withstand the rigors of lethal ischemia in vitro as well as posttransplantation. This review summarizes the past and present novel approaches of ischemic preconditioning, pharmacological and genetic manipulation using preconditioning mimetics, recombinant growth factor protein treatment, and reprogramming of stem cells to overexpress survival signaling molecules, microRNAs, and trophic factors for intracrine, autocrine, and paracrine effects on cytoprotection.

Bradykinin‐mediated Ca2+ signalling regulates cell growth and mobility in human cardiac c‐Kit+ progenitor cells

“…Previous studies have explored different strategies to enhance the survival rate of the donor cells using growth factor genes24 or preconditioning donor stem cells with different interventions including nitric oxide donor,25 HO‐1 inducer CoPP26 and exposure to hypoxia 27, 28. Our recent report10 and the present study demonstrated that the endogenous peptide bradykinin can initiate proliferation and migration of human cardiac c‐Kit + progenitor cells.…”

Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways

“…Pharmacological pretreatment has been shown to be a rational approach to reinforce the cells to withstand the ischemic and reperfusion injury environment. 5) Tetramethylpyrazine (TMP), a biologically active alkaloid extracted from Ligusticum chuanxiong HORT (Umbelliferae), has been widely used in China for the treatment of cardiovascular and cerebrovascular diseases. 6) Its effects are mainly related to its antioxidative, anti-apoptosis, and anti-inflammatory actions.…”

The role of the microenvironment on the fate of adult stem cells

“…Massive cell death thus occurs during transplantation and following engraftment, which significantly lowers the effectiveness of the clinical therapy. The simulated hypoxia microenvironment triggers the improved survival of the SCs in vitro and after transplantation [62,64]. Studies show that sub-lethal levels of hypoxia can significantly increase the tolerance of treated cells to apoptotic and other insults in vitro as well as in the harsh environments of the ischemic and adjacent regions.…”