Regeneration of the ischemic brain by engineered stem cells: fuelling endogenous repair processes. Brain Res Rev

Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Brain Research Reviews (Impact Factor: 5.93). 05/2009; 61(1):1-13. DOI: 10.1016/j.brainresrev.2009.03.003
Source: PubMed

ABSTRACT After ischemic brain injury various cell types including neurons, glia and endothelial cells are damaged and lose their function. Effective regeneration of brain tissue requires that all these cell types have to be replenished and combined to form a new functional network. Recent advances in regenerative medicine show the ability of stem cells to differentiate into various cell lineages. Several types of stem cells have been used to treat ischemic brain injury in rodent models including neuronal stem cells, mesenchymal stem cells and hematopoietic stem cells. Although these studies show promising results, it remains to be determined whether the beneficial effect of cell-based therapies in ischemic brain injury results from direct replacement of damaged cells by the transplanted cells. On the basis of the current literature we propose that neuroprotection by activation of anti-apoptotic mechanisms as well as improvement of the trophic milieu necessary for endogenous repair processes may be more important mechanisms underlying the improved functional outcome after stem cell treatment. Transplantation of native unmodified stem cells as such may not be sufficient to boost repair mechanisms provided by the endogenous stem cell population. An important aim of this review is to discuss the literature on the possible enhancement of regenerative function by combining stem cell transplantation with gene transduction into stem cells to enhance their regenerative and neuroprotective therapeutic potential. Finally, we briefly discuss the possibility of translation of this therapy to the clinic.

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Available from: Cindy Van Velthoven, Aug 18, 2014
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    • "Although exogenous administration of stem cells seems beneficial for the preterm ischemic brain, the alternative of pharmacologically potentiating the endogenous regenerative capacity after injury remains appealing as biological risks, logistics and costs remain as potential obstacles for exogenous stem cell therapy (Gortner et al., 2012). In preterm infants especially, the brain and other tissues possess high numbers of regenerative stem cells (Bennet et al., 2012; Titomanlio et al., 2011; van Velthoven et al., 2009). Pharmacological interventions aimed at mobilizing these stem cells after injury form a promising prospect in the preterm environment (Gortner et al., 2012). "
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    • "Current data suggest that the contribution of MSC differentiation is limited due to poor engraftment and survival of MSCs at the site of injury. Given these limitations, it has been proposed that MSC paracrine signaling is the primary mechanism accounting for the beneficial effects of MSCs on responses to injury such as inflammation, angiogenesis, and fibroproliferation [14] [15] [16] [17] [18] [19] [20] [21]. This hypothesis is further supported by the observation that MSCconditioned medium also enhances tissue repair [21] [22]. "
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    • "Orthotopic MSCs support hematopoietic stem cells to differentiate into mature blood cells by secretion of cytokines and growth factors. In the injured brain, transplanted MSCs are thought to improve endogenous repair processes by release of growth and differentiation factors enhancing the local trophic milieu (Li et al., 2002; Qu et al., 2007; van Velthoven et al., 2009). It has also been suggested that MSCs can differentiate into neurons and oligodendrocytes and thereby contribute to repair of the injured brain (Mezey et al., 2000; Shen et al., 2007). "
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