期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 64, 期 2, 页码 185-199出版社
HUMANA PRESS INC
DOI: 10.1007/s12031-017-1008-8
关键词
CD45(+) pan-hematopoietic cells; Vaginal and cesarean deliveries; Neurotherapeutic effect; Transplantation; Traumatic brain injury; Umbilical cord blood
资金
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- David R. Bloom Center for Pharmacy
- Dr. Adolf and Klara Bretler Center for Research in Molecular Pharmacology and Therapeutics at the Hebrew University of Jerusalem, Israel
Human umbilical cord blood (HUCB) transplantation has become an alternative cell therapy for hematological and oncological malignancies in the clinic and is considered for neurological disorders. The heterogeneity in the content of the different stem and progenitor cells composing HUCB mononuclear cells (MNC) may influence their engraftment and neurotherapeutic effect. We hypothesized that CD45 pan-hematopoietic marker expression is heterogeneous in MNC, and therefore, CD45(+) subpopulation enrichment for neurotherapy may provide a tool to overcome cellular variance in different HUCB units. We employed an immunomagnetic separation method to isolate and characterize HUCB CD45(+) pan-hematopoietic subpopulation and to investigate whether the vaginal or cesarean deliveries influence their neurotherapeutic effect in a traumatic brain injury (TBI) mouse model. Adult C57BL/6J male mice were subjected to moderate TBI and intravenously xenotransplanted with 1 x 10(6) CD45(+) cells derived from either vaginal or cesarean HUCB units. A large heterogeneity in the expression of CD45 marker in MNC, both in vaginal and cesarean HUCB units, was found, regardless of the number of live births. A higher expression of hematopoietic markers was found in the CD45(+) subpopulation while low expressional levels of typical mesenchymal markers were detected. Neurotherapeutic effects, evaluated with an established neurological severity score and novel object recognition test, indicated improved functional motor and memory recovery and found independent of delivery type. Cytokine analysis in extracts of TBI brain cortices indicated an acute immunomodulatory effect by HUCB CD45(+) subpopulation upon xenotransplantation. These results may provide insights to CD45 marker as a predictor of HUCB units' quality for neurotherapy in TBI.
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