Determination of the Therapeutic Time Window for Human Umbilical Cord Blood Mononuclear Cell Transplantation following Experimental Stroke in Rats
- 1 June 2012
- journal article
- research article
- Published by SAGE Publications in Cell Transplantation
- Vol. 21 (6), 1199-1211
- https://doi.org/10.3727/096368911x589609
Abstract
Experimental treatment strategies using human umbilical cord blood mononuclear cells (hUCB MNCs) represent a promising option for alternative stroke therapies. An important point for clinical translation of such treatment approaches is knowledge on the therapeutic time window. Although expected to be wider than for thrombolysis, the exact time window for hUCB MNC therapy is not known. Our study aimed to determine the time window of intravenous hUCB MNC administration after middle cerebral artery occlusion (MCAO). Male spontaneously hypertensive rats underwent MCAO and were randomly assigned to hUCB MNC administration at 4, 24, 72, and 120 or 14 days. Influence of cell treatment was observed by magnetic resonance imaging on days 1, 8, and 29 following MCAO and by assessment of functional neurological recovery. On day 30, brains were screened for glial scar development and presence of hUCB MNCs. Further, influence of hUCB MNCs on necrosis and apoptosis in postischemic neural tissue was investigated in hippocampal slices cultures. Transplantation within a 72-h time window resulted in an early improvement of functional recovery, paralleled by a reduction of brain atrophy and diminished glial scarring. Cell transplantation 120 h post-MCAO only induced minor functional recovery without changes in the brain atrophy rate and glial reactivity. Later transplantation (14 days) did not show any benefit. No evidence for intracerebrally localized hUCB MNCs was found in any treatment group. In vitro hUCB MNCs were able to significantly reduce postischemic neural necrosis and apoptosis. Our results for the first time indicate a time window of therapeutic hUCB MNC application of at least 72 h. The time window is limited, but wider than compared to conventional pharmacological approaches. The data furthermore confirms that differentiation and integration of administered cells is not a prerequisite for poststroke functional improvement and lesion size reduction.Keywords
This publication has 41 references indexed in Scilit:
- Cord blood administration induces oligodendrocyte survival through alterations in gene expressionBrain Research, 2010
- Human Umbilical Cord Blood Cells Decrease Microglial Survival In VitroStem Cells and Development, 2010
- Delayed treatments for stroke influence neuronal death in rat organotypic slice cultures subjected to oxygen glucose deprivationNeuroscience, 2009
- Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic StrokeStroke, 2009
- Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+stem cellsBMC Neuroscience, 2008
- Evidence for neuroprotective properties of human umbilical cord blood cells after neuronal hypoxia in vitroBMC Neuroscience, 2008
- Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brainBMC Neuroscience, 2008
- Development of cerebral infarction, apoptotic cell death and expression of X-chromosome-linked inhibitor of apoptosis protein following focal cerebral ischemia in ratsLife Sciences, 2006
- Human umbilical cord blood cells express neurotrophic factorsNeuroscience Letters, 2005
- Nervous system–derived chondroitin sulfate proteoglycans regulate growth cone morphology and inhibit neurite outgrowth: A light, epifluorescence, and electron microscopy studyMicroscopy Research and Technique, 2001