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Assessment of neuroprotective effects of human umbilical cord blood mononuclear cell subpopulations in vitro and in vivo

: Boltze, Johannes; Reich, Doreen M.; Hau, Susann; Reymann, Klaus G.; Strassburger, Maria; Lobsien, Donald; Wagner, Daniel-Christoph; Kamprad, Manja; Stahl, Tobias

Abstract (HTML; )

Cell Transplantation 21 (2012), Nr.4, S.723-737
ISSN: 0963-6897
ISSN: 1555-3892
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IZI ()
stroke; cell transplantation; MRI; cell therapy; neuroprotection

Experimental transplantation of human umbilical cord blood (hUCB) mononuclear cells (MNCs) in rodent stroke models revealed the therapeutic potential of these cells. However, effective cells within the heterogeneous MNC population and their modes of action are still under discussion. MNCs and MNC fractions enriched (CD34?) or depleted (CD34?) for CD34-expressing stem/progenitor cells were isolated from hUCB. Cells were transplanted intravenously following middle cerebral artery occlusion in spontaneously hypertensive rats and directly or indirectly co-cultivated with hippocampal slices previously subjected to oxygen and glucose deprivation. Application of saline solution or a human T-cell line served as controls. In vivo, MNCs, CD34? and CD34? cells reduced neurofunctional deficits and diminished lesion volume as determined by magnetic resonance imaging. MNCs were superior to other fractions. However, human cells could not be identified in brain tissue 29 days after stroke induction. Following direct application on post-ischemic hippocampal slices, MNCs reduced neural damage throughout a three day observation period. CD34? cells provided transient protection for two days. The CD34? fraction, in contrast to in vivo results, failed to reduce neural damage. Direct co-cultivation of MNCs was superior to indirect co-cultivation of equal cell numbers. Indirect application of up to ten-fold MNC concentrations enhanced neuroprotection to a level comparable to direct co-cultivation. After direct application, MNCs migrated into the slices. Flow cytometric analysis of migrated cells revealed that the CD34? cells within MNCs were preferably attracted by damaged hippocampal tissue. Our study suggests that MNCs provide the most prominent neuroprotective effect with CD34? cells seeming to be particularly involved in the protective action of MNCs. CD34? cells preferentially home to neural tissue in vitro, but are not superior concerning the overall effect, implying that there is another, still undiscovered protective cell population. Furthermore, MNCs did not survive in the ischemic brain for longer periods without immunosuppression.