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The Journal of Neuroscience, March 29, 2006, 26(13):3444-3453; doi:10.1523/JNEUROSCI.5165-05.2006

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Neurobiology of Disease
Intracerebral Peripheral Blood Stem Cell (CD34⁺) Implantation Induces Neuroplasticity by Enhancing 1 Integrin-Mediated Angiogenesis in Chronic Stroke Rats

Woei-Cherng Shyu,^1 * Shinn-Zong Lin,^1 * Ming-Fu Chiang,² Ching-Yuan Su,³ and Hung Li^3,4

¹Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan 970, ²Department of Neurosurgery, Mackay Memorial Hospital, Mackay Junior College of Nursing, Taipei, Taiwan 112, ³Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 115, and ⁴Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan 112

Correspondence should be addressed to Dr. Hung Li, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 115. Email: hungli{at}ccvax.sinica.edu.tw

Although stem cell-based treatments for stroke and other neurodegenerative diseases have advanced rapidly, there are still few clinical treatments available. In this study, rats receiving intracerebral peripheral blood hematopoietic stem cell (CD34⁺) (PBSC) transplantation showed much more improvement in neurological function after chronic cerebral ischemia in comparison with vehicle-treated control rats. Using laser-scanning confocal microscopy, implanted PBSCs were seen to differentiate into glial cells [GFAP⁺ (glial fibrillary acidic protein-positive)], neurons [Nestin⁺, MAP-2⁺ (microtubule-associated protein 2-positive), Neu-N⁺ (neuronal nuclear antigen-positive)], and vascular endothelial cells [vWF⁺ (von Willebrand factor-positive)], thereby enhancing neuroplastic effects in the ischemic brain. Cortical neuronal activity, as evaluated by ¹H-MRS (proton magnetic resonance spectroscopy), also increased considerably in PBSC-treated rats compared with a vehicle-treated control group. In addition, PBSC implantation promoted the formation of new vessels, thereby increasing the local cortical blood flow in the ischemic hemisphere. These observations may be explained by the involvement of stem cell-derived macrophage/microglial cells, and 1 integrin expression, which might enhance this angiogenic architecture over the ischemic brain. Furthermore, quantitative reverse transcription-PCR analysis showed significantly increased modulation of neurotrophic factor expression in the ischemic hemisphere of the PBSC-transplanted rats compared with vehicle-treated control rats. Thus, intracerebral PBSC transplantation might have potential as a therapeutic strategy for treating cerebrovascular diseases.

Key words: peripheral blood hematopoietic stem cells (PBSCs); CD34⁺; chronic stroke animal model; neuroplasticity; angiogenesis; 1 integrin

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Received Sept. 23, 2005; revised Jan. 20, 2006; accepted Jan. 25, 2006.

Correspondence should be addressed to Dr. Hung Li, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 115. Email: hungli{at}ccvax.sinica.edu.tw

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