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Table 1 Overview of different approaches for mesenchymal stem cell modulation in order to increase cell survival

From: Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

General effect Strategy Reference
Upregulation of different pro-survival and pro-angiogenic genes (HIF1α, SDF1α/CXCR4, EPO, VEGF, BDNF, GDNF) Hypoxic preconditioning [112, 113]
Addition of factors to the culture medium [122, 124, 133]
Genetic modification to induce gene overexpression [125, 126, 129132]
Physical protection of MSCs against hypoxia Oxygen supply via oxygen generating scaffolds and biomaterials [127, 128]
Stimulation of PI3K/Akt pathway to prevent apoptosis Treatment with chemokines (for example, SDF1α) [138]
Knockout of TLR4 [137]
Overexpression of genes involved in apoptosis [139]
Downregulation of caspase 3 activity to prevent apoptosis Treatment with compounds (carvedilol, salvianolic acid) that block the activity [140, 141]
Decreased apoptosis Down- or upregulation of microRNA [142]
  1. BDNF, brain-derived neurotrophic factor; EPO, erythropoietin; GDNF, glial cell line-derived neurotrophic factor; HIF, hypoxia-inducible factor; MSC, mesenchymal stem cell; PI3K, phosphoinositide 3-kinase; SDF, stromal-derived factor; TLR, Toll-like receptor; VEGF, vascular endothelial growth factor.