Multi-germ layer lineage central nervous system repair: Nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain

Sudhakar Vadivelu, Marina M. Platik, Luke Choi, Molly L. Lacy, Aarti R. Shah, Yun Qu, Terrence F. Holekamp, Daniel Becker, David I. Gottlieb, Jeffrey M. Gidday, John W. McDonald

Research output: Contribution to journalArticle

Abstract

Object. To restore proper function to a damaged central nervous system (CNS) through transplantation, it is necessary to replace both neural and nonneural elements that arise from different germ layers in the embryo. Mounting evidence indicates the importance of signals related to vasculogenesis in governing neural proliferation and differentiation in early CNS development. Here, the authors examined whether embryonic stem cell (ESC) - derived progenitors can selectively generate both neural and endothelial cells after transplantation in the damaged CNS. Methods. Injections of 20 nmol N-methyl-D-aspartate created a unilateral striatal injury in 7-day-old rats. One week postinjury, murine ESCs, neural-induced with retinoic acid, were transplanted into the injured striatum. Histological staining, laser confocal microscopy, and transmission electron microscopy of grafted ESCs were performed 1 week posttransplantation. Conclusions. Transplanted ESCs differentiated into neural cells, which segregated into multiple pools and formed neurons that conformed to host cytoarchitecture. The ESCs also generated endothelial cells, which integrated with host cells to form chimeric vasculature. The combination of ESC pluripotentiality and multiple germ layer differentiation provides a new conceptual framework for CNS repair.

Original languageEnglish (US)
Pages (from-to)124-135
Number of pages12
JournalJournal of neurosurgery
Volume103
Issue number1
DOIs
StatePublished - Jul 2005

Keywords

  • Differentiation
  • Endothelial cell
  • Neural element
  • Pluripotent cell
  • Progenitor cell
  • Rat
  • Regeneration

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Vadivelu, S., Platik, M. M., Choi, L., Lacy, M. L., Shah, A. R., Qu, Y., Holekamp, T. F., Becker, D., Gottlieb, D. I., Gidday, J. M., & McDonald, J. W. (2005). Multi-germ layer lineage central nervous system repair: Nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain. Journal of neurosurgery, 103(1), 124-135. https://doi.org/10.3171/jns.2005.103.1.0124