Authors: Daadi, Marcel M.; Lee, Sang Hyung; Arac, Ahmet; Grueter, Brad A.; Bhatnagar, Rishi; Maag, Anne-Lise; Schaar, Bruce; Malenka, Robert C.; Palmer, Theo D.; Steinberg, Gary K.

Source: Cell Transplantation, Volume 18, Number 7, 2009 , pp. 815-826(12)

Publisher: Cognizant Communication Corporation

Abstract:

Currently there are no effective treatments targeting residual anatomical and behavioral deficits resulting from stroke. Evidence suggests that cell transplantation therapy may enhance functional recovery after stroke through multiple mechanisms. We used a syngeneic model of neural transplantation to explore graft-host communications that enhance cellular engraftment.The medial ganglionic eminence (MGE) cells were derived from 15-day-old transgenic rat embryos carrying green fluorescent protein (GFP), a marker, to easily track the transplanted cells. Adult rats were subjected to transient intraluminal occlusion of the medial cerebral artery. Two weeks after stroke, the grafts were deposited into four sites, along the rostro-caudal axis and medially to the stroke in the penumbra zone. Control groups included vehicle and fibroblast transplants. Animals were subjected to motor behavioral tests at 4 week posttransplant survival time. Morphological analysis demonstrated that the grafted MGE cells differentiated into multiple neuronal subtypes, established synaptic contact with host cells, increased the expression of synaptic markers, and enhanced axonal reorganization in the injured area. Initial patch-clamp recording demonstrated that the MGE cells received postsynaptic currents from host cells. Behavioral analysis showed reduced motor deficits in the rotarod and elevated body swing tests. These findings suggest that graft-host interactions influence the fate of grafted neural precursors and that functional recovery could be mediated by neurotrophic support, new synaptic circuit elaboration, and enhancement of the stroke-induced neuroplasticity.

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Keywords: Cell transplantation; Graft-host interactions; Stroke-injured environment; Synaptogenesis; Axonal sprouting; Neuroplasticity

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096368909X470829

Affiliations: 1: Department of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA. mdaadi@stanford.edu

Publication date: 2009-07-01

More about this publication?

• Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
  

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• In this Subject: Anatomy & Physiology ,  Biology ,  Biotechnology ,  Pharmacology ,  Surgery
• By this author: Daadi, Marcel M. ;  Lee, Sang Hyung ;  Arac, Ahmet ;  Grueter, Brad A. ;  Bhatnagar, Rishi ;  Maag, Anne-Lise ;  Schaar, Bruce ;  Malenka, Robert C. ;  Palmer, Theo D. ;  Steinberg, Gary K.

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