Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy

Abstract

Abstract-Cell-based therapies for the prevention and treatment of cardiac dysfunction offer the potential to significantly modulate cardiac function and improve outcomes in patients with cardiovascular disease. To date several clinical studies have suggested the potential efficacy of several different stem cell types; however, the benefits seen in clinical trials have been inconsistent and modest. In parallel, preclinical studies have identified key events in the process of cell-based myocardial repair, including stem cell homing, engraftment, survival, paracrine factor release, and differentiation that need to be optimized to maximize cardiac repair and function. The inconsistent and modest benefits seen in clinical trials combined with the preclinical identification of mediators responsible for key events in cell-based cardiac repair offers the potential for cell-based therapy to advance to cell-based gene therapy in an attempt to optimize these key events in the hope of maximizing clinical benefit. Below we discuss potential key events in cardiac repair and the mediators of these events that could be of potential interest for genetic enhancement of stem cell-based cardiac repair. (Circ Res.

Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells

“…1 However, clinical trials of stem cell therapy have shown a slight improvement of cardiac function, and if some improvement was observed, it is now thought to be attributable to paracrine effects but not transdifferentiation of transplanted stem cells into cardiomyocytes of transplanted cells. 2 The major obstacles to current stem cell therapy are as follows. First, the efficiency of cardiomyocyte differentiation of cultured and transplanted stem cells is quite low.…”

Biomaterials to Enhance Stem Cell Function in the Heart

“…77 Gene therapy currently lacks precise quantitative control of expression, but some applications may tolerate broad ranges of overexpression. Biomaterials can sustain delivery, protect plasmid DNA from degradation, and increase transfection efficiency.…”

Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

“…How to improve the survival of grafted MSCs is a demanding task for further research. [3][4][5] One strategy is to manipulate the expression of key genes involved in the cell survival. In the previous studies, genetic modification of MSCs overexpressing some pro-survival genes, such as Akt, Bcl-2, stromal-derived factor 1 (SDF-1), and chemokine (c-c motif) receptor-1, had been tested to improve the survival of grafted cells in vivo but with little efficacy.…”

“…In the previous studies, genetic modification of MSCs overexpressing some pro-survival genes, such as Akt, Bcl-2, stromal-derived factor 1 (SDF-1), and chemokine (c-c motif) receptor-1, had been tested to improve the survival of grafted cells in vivo but with little efficacy. 3,6 Small interfering RNA (siRNA)-mediated silencing of oxidative injuryrelated gene expression may open a novel possibility for enhancing cell survival. As an oxygen-dependent gene, the prolyl hydroxylase domain protein 2 (PHD2) gene regulates hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-κB (NF-κB), which submit your manuscript | www.dovepress.com…”