PMID- 16596121 OWN - NLM STAT- MEDLINE DCOM- 20070917 LR - 20200730 IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 27 IP - 1 DP - 2007 Jan TI - Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. PG - 6-13 AB - Bone marrow stromal cells (BMSCs) facilitate functional recovery in rats after stroke when administered acutely (1 day) or subacutely (7 days). In this study, we postponed the time of cell transplantation to 1 month after stroke. Female retired breeder rats were subjected to 2 h of middle cerebral artery occlusion (MCAo). Male BMSCs (3 x 10(6)) or phosphate-buffered saline were administered intravenously, and the animals were killed 3 months later. An additional population of nontreated rats was killed at 1 month after MCAo. Significant recovery of behavior was found in BMSC-treated rats beginning at 1 month after cell injection in the modified neurologic severity score test and the adhesive-removal test compared with control animals (P<0.05). In situ hybridization showed that BMSCs survived and preferentially localized to the ipsilateral hemisphere. Double staining revealed that approximately 13% and 6% Y-chromosome-positive cells expressed the astrocyte marker, glial fibrillary acidic protein, and the neuronal marker, microtubule-associated protein-2, respectively. In addition, BMSC treatment reduced scar thickness, and increased the number of proliferating cells and oligodendrocyte precursor cells along the subventricular zone in the ipsilateral hemisphere. Expression of the chemokine stromal-cell-derived factor-1 (SDF-1) was significantly increased along the ischemic boundary zone compared with the corresponding areas in the contralateral hemisphere at 1 month and 4 months (P<0.01) after stroke. The SDF-1 receptor, CXC-chemokine receptor-4 (CXCR4), was expressed in BMSCs both in vitro and in vivo. Our data show that the time window of BMSC therapy is at least 1 month after stroke; the interaction of SDF-1/CXCR4 may contribute to the trafficking of transplanted BMSCs. FAU - Shen, Li Hong AU - Shen LH AD - Department of Neurology, Henry Ford Health Sciences Center, Henry Ford Hospital, Detroit, Michigan 48202, USA. FAU - Li, Yi AU - Li Y FAU - Chen, Jieli AU - Chen J FAU - Zacharek, Alex AU - Zacharek A FAU - Gao, Qi AU - Gao Q FAU - Kapke, Allissa AU - Kapke A FAU - Lu, Mei AU - Lu M FAU - Raginski, Kim AU - Raginski K FAU - Vanguri, Padmayathy AU - Vanguri P FAU - Smith, Alan AU - Smith A FAU - Chopp, Michael AU - Chopp M LA - eng GR - P01 NS042345/NS/NINDS NIH HHS/United States GR - R01 NS045041/NS/NINDS NIH HHS/United States GR - P01 NS23393/NS/NINDS NIH HHS/United States GR - R01 NS45041/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060405 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Biomarkers) RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (Immunoglobulins) RN - 0 (Membrane Glycoproteins) RN - 0 (Nptn protein, rat) RN - 0 (Receptors, CXCR4) SB - IM MH - Animals MH - Behavior, Animal/physiology MH - Biomarkers MH - *Bone Marrow Transplantation MH - Chemokine CXCL12 MH - Chemokines, CXC/blood MH - Female MH - Immunoglobulins/blood MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Infarction, Middle Cerebral Artery/pathology MH - Male MH - Membrane Glycoproteins/blood MH - Physical Stimulation MH - Psychomotor Performance/physiology MH - Rats MH - Rats, Wistar MH - Receptors, CXCR4/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stroke/pathology/psychology/*therapy MH - Stromal Cells/*transplantation EDAT- 2006/04/06 09:00 MHDA- 2007/09/18 09:00 CRDT- 2006/04/06 09:00 PHST- 2006/04/06 09:00 [pubmed] PHST- 2007/09/18 09:00 [medline] PHST- 2006/04/06 09:00 [entrez] AID - 9600311 [pii] AID - 10.1038/sj.jcbfm.9600311 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2007 Jan;27(1):6-13. doi: 10.1038/sj.jcbfm.9600311. Epub 2006 Apr 5.