| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Neurology (Drs. Li, J. Chen, X. Chen, Wang, and Zhang), the Bone Marrow Transplant Program (Drs. Gautam, Xu, and Janakiraman), Division of Hematology and Medical Oncology, and Biostatistics and Research Epidemiology (Dr. Lu), Henry Ford Health Sciences Center, Detroit; and the Department of Physics (Dr. Chopp and M. Katakowski), Oakland University, Rochester, MI.
Address correspondence and reprint requests to Michael Chopp, PhD, Henry Ford Hospital, Neurology Department, E&R 3056, 2799 West Grand Boulevard, Detroit, MI 48202; e-mail: chopp{at}neuro.hfh.edu
Objective: To test the effect of IV-injected human bone marrow stromal cells (hMSC) on neurologic functional deficits after stroke in rats.
Methods: Rats were subjected to transient middle cerebral artery occlusion and IV injected with 3 x 106 hMSC 1 day after stroke. Functional outcome was measured before and 1, 7, and 14 days after stroke. Mixed lymphocyte reaction and the development of cytotoxic T lymphocytes measured the immune rejection of hMSC. A monoclonal antibody specific to human cellular nuclei (mAb1281) was used to identify hMSC and to measure neural phenotype. ELISA analyzed neurotrophin levels in cerebral tissue from hMSC-treated or nontreated rats. Bromodeoxyuridine injections were used to identify newly formed cells.
Results: Significant recovery of function was found in rats treated with hMSC at 14 days compared with control rats with ischemia. Few (1 to 5%) hMSC expressed proteins phenotypic of brain parenchymal cells. Brain-derived neurotrophic factor and nerve growth factor significantly increased, and apoptotic cells significantly decreased in the ischemic boundary zone; significantly more bromodeoxyuridine-reactive cells were detected in the subventricular zone of the ischemic hemisphere of rats treated with hMSC. hMSC induced proliferation of lymphocytes without the induction of cytotoxic T lymphocytes.
Conclusion: Neurologic benefit resulting from hMSC treatment of stroke in rats may derive from the increase of growth factors in the ischemic tissue, the reduction of apoptosis in the penumbral zone of the lesion, and the proliferation of endogenous cells in the subventricular zone.
This article has been cited by other articles:
|
|
 |
|
  C.-H. Song, O. Honmou, N. Ohsawa, K. Nakamura, H. Hamada, H. Furuoka, R. Hasebe, and M. Horiuchi Effect of Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells on Mice Infected with Prions J. Virol., June 1, 2009; 83(11): 5918 - 5927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Wang, J. E. Dennis, A. Awadallah, L. A. Solchaga, J. Molter, Y. Kuang, N. Salem, Y. Lin, H. Tian, J. A. Kolthammer, et al. Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging Physiol Genomics, March 3, 2009; 37(1): 23 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-S. Cho, H.-K. Park, H.-Y. Park, J. S. Jung, S.-G. Jeon, Y.-K. Kim, and H. J. Roh IFATS Collection: Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells in an Allergic Rhinitis Mouse Model Stem Cells, January 1, 2009; 27(1): 259 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Iwanami, M. Mogi, J.-M. Li, K. Tsukuda, L.-J. Min, A. Sakata, T. Fujita, M. Iwai, and M. Horiuchi Deletion of Angiotensin II Type 2 Receptor Attenuates Protective Effects of Bone Marrow Stromal Cell Treatment on Ischemia-Reperfusion Brain Injury in Mice * Supplemental Materials and Methods Stroke, September 1, 2008; 39(9): 2554 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Kim, S.-W. Yoo, T.-S. Park, S.-C. Ahn, H.-S. Jeong, J.-W. Kim, D.-Y. Chang, K.-G. Cho, S. U. Kim, Y. Huh, et al. Neural Induction with Neurogenin1 Increases the Therapeutic Effects of Mesenchymal Stem Cells in the Ischemic Brain Stem Cells, September 1, 2008; 26(9): 2217 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Lee, J. E. Dennis, and S. L. Gerson Imaging Stem Cell Implant for Cellular-Based Therapies Experimental Biology and Medicine, August 1, 2008; 233(8): 930 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Shyu, S.-Z. Lin, P.-S. Yen, C.-Y. Su, D.-C. Chen, H.-J. Wang, and H. Li Stromal Cell-Derived Factor-1{alpha} Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 834 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Love, F. Wang, J. Dennis, A. Awadallah, N. Salem, Y. Lin, A. Weisenberger, S. Majewski, S. Gerson, and Z. Lee Imaging of Mesenchymal Stem Cell Transplant by Bioluminescence and PET J. Nucl. Med., December 1, 2007; 48(12): 2011 - 2020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Isakova, K. Baker, M. DuTreil, J. Dufour, D. Gaupp, and D. G. Phinney Age- and Dose-Related Effects on MSC Engraftment Levels and Anatomical Distribution in the Central Nervous Systems of Nonhuman Primates: Identification of Novel MSC Subpopulations That Respond to Guidance Cues in Brain Stem Cells, December 1, 2007; 25(12): 3261 - 3270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cui, J. Chen, A. Zacharek, Y. Li, C. Roberts, A. Kapke, S. Savant-Bhonsale, and M. Chopp Nitric Oxide Donor Upregulation of Stromal Cell-Derived Factor-1/Chemokine (CXC Motif) Receptor 4 Enhances Bone Marrow Stromal Cell Migration into Ischemic Brain After Stroke Stem Cells, November 1, 2007; 25(11): 2777 - 2785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Shen, Y. Li, J. Chen, Y. Cui, C. Zhang, A. Kapke, M. Lu, S. Savant-Bhonsale, and M. Chopp One-Year Follow-Up After Bone Marrow Stromal Cell Treatment in Middle-Aged Female Rats With Stroke Stroke, July 1, 2007; 38(7): 2150 - 2156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. R. Santhanam, L. A. Smith, T. He, K. A. Nath, and Z. S. Katusic Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2 Circ. Res., May 11, 2007; 100(9): 1379 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Baker, V. Sica, L. M. Work, S. Williams-Ignarro, F. de Nigris, L. O. Lerman, A. Casamassimi, A. Lanza, C. Schiano, M. Rienzo, et al. Brain protection using autologous bone marrow cell, metalloproteinase inhibitors, and metabolic treatment in cerebral ischemia PNAS, February 27, 2007; 104(9): 3597 - 3602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bliss, R. Guzman, M. Daadi, and G. K. Steinberg Cell Transplantation Therapy for Stroke Stroke, February 1, 2007; 38(2): 817 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-C. Shyu, C.-P. Chen, S.-Z. Lin, Y.-J. Lee, and H. Li Efficient Tracking of Non-Iron-Labeled Mesenchymal Stem Cells With Serial MRI in Chronic Stroke Rats Stroke, February 1, 2007; 38(2): 367 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jomura, M. Uy, K. Mitchell, R. Dallasen, C. J. Bode, and Y. Xu Potential Treatment of Cerebral Global Ischemia with Oct-4+ Umbilical Cord Matrix Cells Stem Cells, January 1, 2007; 25(1): 98 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, O. Honmou, K. Harada, K. Nakamura, K. Houkin, H. Hamada, and J. D. Kocsis Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia Brain, October 1, 2006; 129(10): 2734 - 2745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kim, S. W. Cho, S. J. Her, J. Y. Yang, S. W. Kim, S. Y. Kim, and C. S. Shin Retrovirus-Mediated Gene Transfer of Receptor Activator of Nuclear Factor-{kappa}B-Fc Prevents Bone Loss in Ovariectomized Mice Stem Cells, July 1, 2006; 24(7): 1798 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Dunbar, M. I. Sandstrom, J. Rossignol, and L. Lescaudron Neurotrophic Enhancers as Therapy for Behavioral Deficits in Rodent Models of Huntington's Disease: Use of Gangliosides, Substituted Pyrimidines, and Mesenchymal Stem Cells. Behav Cogn Neurosci Rev, June 1, 2006; 5(2): 63 - 79. [Abstract] [PDF]
|
|
|
|
|
|
S. Francois, M. Bensidhoum, M. Mouiseddine, C. Mazurier, B. Allenet, A. Semont, J. Frick, A. Sache, S. Bouchet, D. Thierry, et al. Local Irradiation Not Only Induces Homing of Human Mesenchymal Stem Cells at Exposed Sites but Promotes Their Widespread Engraftment to Multiple Organs: A Study of Their Quantitative Distribution After Irradiation Damage Stem Cells, April 1, 2006; 24(4): 1020 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stagg, S. Pommey, N. Eliopoulos, and J. Galipeau Interferon-{gamma}-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell Blood, March 15, 2006; 107(6): 2570 - 2577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kawada, S. Takizawa, T. Takanashi, Y. Morita, J. Fujita, K. Fukuda, S. Takagi, H. Okano, K. Ando, and T. Hotta Administration of Hematopoietic Cytokines in the Subacute Phase After Cerebral Infarction Is Effective for Functional Recovery Facilitating Proliferation of Intrinsic Neural Stem/Progenitor Cells and Transition of Bone Marrow-Derived Neuronal Cells Circulation, February 7, 2006; 113(5): 701 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ikeda, N. Nonoguchi, M. Z. Zhao, T. Watanabe, Y. Kajimoto, D. Furutama, F. Kimura, M. Dezawa, R. S. Coffin, Y. Otsuki, et al. Bone Marrow Stromal Cells That Enhanced Fibroblast Growth Factor-2 Secretion by Herpes Simplex Virus Vector Improve Neurological Outcome After Transient Focal Cerebral Ischemia in Rats Stroke, December 1, 2005; 36(12): 2725 - 2730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Zappia, S. Casazza, E. Pedemonte, F. Benvenuto, I. Bonanni, E. Gerdoni, D. Giunti, A. Ceravolo, F. Cazzanti, F. Frassoni, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy Blood, September 1, 2005; 106(5): 1755 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. E. Sigurjonsson, M.-C. Perreault, T. Egeland, and J. C. Glover Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord PNAS, April 5, 2005; 102(14): 5227 - 5232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Lindvall and Z. Kokaia Recovery and Rehabilitation in Stroke: Stem Cells Stroke, November 1, 2004; 35(11_suppl_1): 2691 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vendrame, J. Cassady, J. Newcomb, T. Butler, K. R. Pennypacker, T. Zigova, C. Davis Sanberg, P. R. Sanberg, and A. E. Willing Infusion of Human Umbilical Cord Blood Cells in a Rat Model of Stroke Dose-Dependently Rescues Behavioral Deficits and Reduces Infarct Volume Stroke, October 1, 2004; 35(10): 2390 - 2395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-C. Shyu, S.-Z. Lin, H.-I Yang, Y.-S. Tzeng, C.-Y. Pang, P.-S. Yen, and H. Li Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor-Stimulated Stem Cells Circulation, September 28, 2004; 110(13): 1847 - 1854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Ji, B. P. He, S. T. Dheen, and S. S. W. Tay Interactions of Chemokines and Chemokine Receptors Mediate the Migration of Mesenchymal Stem Cells to the Impaired Site in the Brain After Hypoglossal Nerve Injury Stem Cells, May 1, 2004; 22(3): 415 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Jeong, K. Chu, K.-H. Jung, S. U. Kim, M. Kim, and J.-K. Roh Human Neural Stem Cell Transplantation Promotes Functional Recovery in Rats With Experimental Intracerebral Hemorrhage Stroke, September 1, 2003; 34(9): 2258 - 2263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, Z. G. Zhang, Y. Li, L. Wang, Y. X. Xu, S. C. Gautam, M. Lu, Z. Zhu, and M. Chopp Intravenous Administration of Human Bone Marrow Stromal Cells Induces Angiogenesis in the Ischemic Boundary Zone After Stroke in Rats Circ. Res., April 4, 2003; 92(6): 692 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Prockop Further proof of the plasticity of adult stem cells and their role in tissue repair J. Cell Biol., March 17, 2003; 160(6): 807 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Moskowitz and E. H. Lo Neurogenesis and Apoptotic Cell Death Stroke, February 1, 2003; 34(2): 324 - 326. [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Rempe and T. A. Kent Using bone marrow stromal cells for treatment of stroke Neurology, August 27, 2002; 59(4): 486 - 486. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
