Determination of the Therapeutic Time Window for Human Umbilical Cord Blood Mononuclear Cell Transplantation Following Experimental Stroke in Rats
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.
No Supplementary Data.
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Human umbilical cord blood (hUCB);
Magnetic resonance imaging;
Document Type: Research Article
Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Leibniz Institute for Neurobiology, Project Group Neuropharmacology, Magdeburg, Germany
Department for Neuroradiology, University of Leipzig, Leipzig, Germany
Department of Neurology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany
Publication date: 2012-06-01
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