Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Abstract

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood-derived CD34 + cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34 + cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.

Improving Outcome after Stroke: Overcoming the Translational Roadblock

“…Stem and progenitor cells from the bone marrow, in particular so-called endothelial progenitor cells, may promote vascular repair, neovascularization and improve endothelial function [54, 55]. Only recently has it become apparent that poststroke angiogenesis can indeed promote regeneration [56, 57].…”

Evaluation of neural plasticity in adult stem cells

“…Similar to in vitro differentiation, in vivo differentiated cells should express the correct complement of neuronal or glial markers, function appropriately, and integrate in the neural circuitry. The last criterion is the most difficult to attain, as many in vivo studies using NSCs have not fully proven true function of NSC-derived neurons in vivo, and it remains to be determined in many cases whether functional benefit is the result of the integration of donor neural cells in the brain or spinal cord, versus trophic effects elaborated by the donor cells that elicit endogenous neural cells to repair the deficit (Chopp & Li 2002;Lu et al 2003;Taguchi et al 2004;Yan et al 2004). For instance, when grafted in the striatum, dopaminergic committed cells mature further and appear to be able to provide functional benefit, even though most of these papers do not demonstrate functional integration (Carvey et al 2001;Tai & Svendsen 2004;Wang et al 2004).…”

Neurorepair versus Neuroprotection in Stroke

“…bone marrow [135, 136]. In animals, the transplants of different stem cells have been reported to partly reverse some behavioral deficits [137,138,139,140,141,142,143,144]. …”