Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat

Journal of Neuroscience Research - Tập 73 Số 6 - Trang 778-786 - 2003
Jieli Chen1, Yi Li2, Mark Katakowski2,3, Xiaoguang Chen2, Lei Wang2, Dunyue Lu4, Mei Lü5, Subhash C. Gautam6, Michael Chopp2,3
1Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA
2Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan
3Department of Physics, Oakland University, Rochester, Michigan
4Department of Neurosurgery,Henry Ford Health Sciences Center,Detroit,Michigan.
5† Department of Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Detroit, Michigan
6Division of Hematology/Oncology, Henry Ford Health Sciences Center, Detroit, Michigan

Tóm tắt

AbstractThe present study investigates the induction of neurogenesis, reduction of apoptosis, and promotion of basic fibroblast growth factor (bFGF) expression as possible mechanisms by which treatment of stroke with bone marrow stromal cells (MSCs) improves neurological functional recovery. Additionally, for the first time, we treated cerebral ischemia in female rats with intraveneous administration of MSCs. Female rats were subjected to 2 hr of middle cerebral artery occlusion (MCAo), followed by an injection of 3 × 106 male (for Y chromosome labeling) rat MSCs or phosphate‐buffered saline (PBS) into the tail vein 24 hr after MCAo. All animals received daily injection of bromodeoxyuridine (BrdU; 50 mg/kg, i.p.) for 13 days after treatment for identification of newly synthesized DNA. Animals were sacrificed at 14 days after MCAo. Behavioral tests (rotarod and adhesive‐removal tests) were performed. In situ hybridization, immunohistochemistry, and terminal deoxynucleotidyltransferase (TdT)‐mediated dUTP‐biotin nick‐end labeling (TUNEL) were performed to identify transplanted MSCs (Y chromosome), BrdU, bFGF, and apoptotic cells in the brain. Significant recovery of behavior was found in MSC‐treated rats at 7 days in the somatosensory test and at 14 days in the motor test after MCAo compared with control, PBS‐treated animals (P < .05). MSCs were found to survive and preferentially localize to the ipsilateral ischemic hemisphere. Significantly more BrdU‐positive cells were located in the subventricular zone (P < .05), and significantly fewer apoptotic cells and more bFGF immunoreactive cell were found in the ischemic boundary area (P < .05) of MSC‐treated rats than in PBS‐treated animals. Here we demonstrate that intravenously administered male MSCs increase bFGF expression, reduce apoptosis, promote endogenous cellular proliferation, and improve functional recovery after stroke in female rats. © 2003 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1002/j.1939-4640.1997.tb01921.x

10.1046/j.0953-816x.2001.01611.x

10.1038/nm747

Ashton BA, 1980, Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo, Clin Orthop, 294

10.1523/JNEUROSCI.21-17-06718.2001

10.1046/j.1460-9568.2002.01891.x

Cai S, 2002, Expression of human VEGF(121) cDNA in mouse bone marrow stromal cells, Chin Med J [English], 115, 914

10.1016/S1096-4959(01)00525-5

10.1038/jcbfm.1992.86

10.1016/S0028-3908(00)00006-X

10.1016/S0022-510X(01)00557-3

10.1161/01.STR.32.4.1005

10.1161/01.RES.0000063425.51108.8D

10.1046/j.1440-1789.2002.00450.x

10.1002/jnr.10334

10.1089/152581601750098372

10.1182/blood.V78.1.110.110

10.1073/pnas.94.8.4080

10.1126/science.279.5356.1528

10.1007/s004010000268

10.1046/j.1460-9568.2002.01892.x

10.1073/pnas.97.4.1823

10.1002/ana.410360402

10.1002/dev.10024

10.1016/S0306-4522(98)00612-5

10.1089/neu.1994.11.187

10.1161/01.STR.28.10.2039

10.1097/00004647-199808000-00009

10.1172/JCI14862

10.1073/pnas.182296499

10.1073/pnas.96.19.10711

10.1126/science.3798108

10.1016/S0002-9440(10)65287-X

10.1002/jlb.64.2.228

10.1038/jcbfm.1995.49

Li Y, 1995, Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat, Am J Pathol, 146, 1045

10.1016/S0022-510X(98)00036-7

10.1097/00004647-200009000-00006

10.1212/WNL.56.12.1666

10.1212/WNL.59.4.514

10.1016/S0169-328X(97)00152-6

10.1097/00005072-199403000-00002

10.1523/JNEUROSCI.18-19-07768.1998

10.1089/089771501316919175

10.1097/00006123-200111000-00031

10.1002/(SICI)1097-4652(199807)176:1<57::AID-JCP7>3.0.CO;2-7

10.1055/s-2001-18818

10.1073/pnas.95.3.1142

10.1002/jor.1100090504

10.1016/0006-8993(86)90261-1

10.1038/jcbfm.1990.47

10.1038/35081577

10.1002/1097-4644(20001215)79:4<672::AID-JCB150>3.0.CO;2-2

10.1038/364713a0

10.1016/S0022-510X(00)00268-9

10.1016/S0306-4522(01)00117-8