Abstract
Objective: To evaluate the therapeutic effect of transplanted glial cell derived neurotrophic factor (GDNF) modified marrow stromal cells (MSCs) on an experimental ischemic brain injury based on the behavioral, morphological, and immunohistochemical observations. Methods: The MSCs from four-week newborn rats were cultured in vitro. The cerebral ischemia and reperfusion model was established in adult Sprague–Dawley (SD) rats by using the suture method. Three days after model establishment, the animals were injected with prepared MSCs via their caudal veins. The animals were then divided into a sham-operation group, ischemia group, MSCs transplantation group, or GDNF+ MSCs transplantation group and were scored for their neurobehavioral manifestations at 3, 14, and 28 days after the transplantation was performed. At this time, the survival condition of intracerebral transplanted cells was measured by laser confocal microscopy while the effect of transplantation on the Generic Digital Beam Former (GDNF) expression in the ischemic brain tissue was evaluated. Results: The MSCs cells transfected with GDNF gene were characterized by green fluorescence. Three days after the transplantation, the animals that underwent the cell transplantation showed significantly better behavioral data than the controls. Fourteen days after transplantation, the animals transplanted with GDNF gene modified MSCs were better than those transplanted with common MSCs. As compared with common MSCs transplantation, GDNF+MSCs transplantation was significantly more effective in reducing apoptotic cell volume and enhancing Bcl-2 expression, which was favorable for the ischemic brain injury. Conclusions: Transplanted GDNF modified MSCs can improve the nervous function and have a protective effect on the ischemic brain injury through reducing apoptotic cell volume and enhancing the expression of anti-apoptotic gene Bcl-2.
Highlights
As a principle component of non-hematopoietic system in bone marrow, marrow stromal cells (MSCs) (Shichinohe et al, 2008; Zacharek et al, 2010; Yilmaz et al, 2011) can express multiple neuron- and gliocyte-specific markers and grow morphological processes similar to that of neural cells when treated with inducers in vitro
glial cell derived neurotrophic factor (GDNF) could reduce the calcium reflux induced by NMDA, a glutamic receptor, via the mitogen activated protein kinase (MAPK) pathway
It was reported that GDNF had a protective effect on the ischemic brain injury by suppressing the production of free radicals and active toxics (Nicole et al, 2001; Horita et al, 2006)
Summary
As a principle component of non-hematopoietic system in bone marrow, marrow stromal cells (MSCs) (Shichinohe et al, 2008; Zacharek et al, 2010; Yilmaz et al, 2011) can express multiple neuron- and gliocyte-specific markers and grow morphological processes similar to that of neural cells when treated with inducers in vitro. This indicates the potential of MSCs to differentiate into neural cells and provides theoretical evidence for cell transplantation in treating ischemic brain injuries. The expressed green fluorescent protein was considered the reporter gene to optimize the transfection condition
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