期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 2, 期 3, 页码 204-216出版社
WILEY
DOI: 10.5966/sctm.2012-0110
关键词
Spinal cord injury; Stem cell transplantation; Fate; Migration; CGRP; Mechanical allodynia; Thermal hyperalgesia
资金
- National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) [R01-NS049885]
- Christopher Reeve Foundation [AAC-2005]
- California Institute for Regenerative Medicine (CIRM) Stem Cell Training Grant [T1-00008]
- University of California's Alliance for Graduate Education
- Professoriate (UCAGEP) Fellowship NSF [HRD0450366]
- CIRM Postdoctoral Training Grant [TG2-01152]
Neural stem cell transplantation may have the potential to yield repair and recovery of function in central nervous system injury and disease, including spinal cord injury (SCI). Multiple pathological processes are initiated at the epicenter of a traumatic spinal cord injury; these are generally thought to make the epicenter a particularly hostile microenvironment. Conversely, the injury epicenter is an appealing potential site of therapeutic human central nervous system-derived neural stem cell (hCNS-SCns) transplantation because of both its surgical accessibility and the avoidance of spared spinal cord tissue. In this study, we compared hCNS-SCns transplantation into the SCI epicenter (EPI) versus intact rostral/caudal (R/C) parenchyma in contusion-injured athymic nude rats, and assessed the cell survival, differentiation, and migration. Regardless of transplantation site, hCNS-SCns survived and proliferated; however, the total number of hCNS-SCns quantified in the R/C transplant animals was twice that in the EPI animals, demonstrating increased overall engraftment. Migration and fate profile were unaffected by transplantation site. However, although transplantation site did not alter the proportion of human astrocytes, EPI transplantation shifted the localization of these cells and exhibited a correlation with calcitonin gene-related peptide fiber sprouting. Critically, no changes in mechanical allodynia or thermal hyperalgesia were observed. Taken together, these data suggest that the intact parenchyma may be a more favorable transplantation site than the injury epicenter in the subacute period post-SCI. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:204-216
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