Preconditioning Strategy in Stem Cell Transplantation Therapy
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REVIEW ARTICLE
Preconditioning Strategy in Stem Cell Transplantation Therapy Shan Ping Yu & Zheng Wei & Ling Wei
Received: 18 December 2012 / Accepted: 27 December 2012 / Published online: 11 January 2013 # Springer Science+Business Media New York 2013
Abstract Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of cell-based therapy. To this end, some recent investigations have sought to benefit from wellknown mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sublethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. S. P. Yu : L. Wei (*) Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Memorial Research Building, Suite 620, Atlanta, GA 30322, USA e-mail: [email protected] S. P. Yu : Z. Wei Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China 100191
It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy. Keywords Stem cell preconditioning . Stroke . Ischemia . Neurodegenerative disorder . Heart attack Abbreviations BDNF Brain-derived neurotrophic factor CoPP Cobalt protoporphyrin Cx43 Connexin-43 CXCR CXC chemokine receptor EPO Erythropoietin ERK Extracellular signal-regulated kinase FAK Focal adhesion kinase GSK-3β Glycogen synthase kinase-3β HIF-1 Hypoxia-inducible factor-1 HSPs Heat shock protein IGF-1 Insulin-like growth factor-1 IL-1β Interleukin-1beta IL-6 Interleukin-6 LPS Lipopolysaccharide miR micro-RNA MMP Matrix metalloproteinase NOS Nitric oxide synthase polyP Poly
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