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We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke\u2010injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, although the exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to demonstrate definitively the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. Thus careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury. J. Comp. Neurol. 515:125\u2013144, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.22038","type":"journal-article","created":{"date-parts":[[2009,3,20]],"date-time":"2009-03-20T17:01:00Z","timestamp":1237568460000},"page":"125-144","source":"Crossref","is-referenced-by-count":158,"title":["Stem cells for ischemic brain injury: A critical review"],"prefix":"10.1002","volume":"515","author":[{"given":"Terry C.","family":"Burns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Verfaillie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter C.","family":"Low","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,27]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Interim State Population Projections","author":"American Association on Aging","year":"2005"},{"key":"e_1_2_8_3_1","unstructured":"American Heart Association.2007.www.americanheart.org. 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