Neuronal differentiation of adipose-derived stem cells and their transplantation for cerebral ischemia.

Objective: To review published data on the biological characteristics, differentiation and applications of adipose-derived stem cells in ischemic diseases. Data Retrieval: A computer-based online search of reports published from January 2005 to June 2012 related to the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia was performed in Web of Science using the key words "adipose-derived stem cells", "neural-like cells", "transplantation", "stroke", and "cerebral ischemia". Selection Criteria: The documents associated with the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia were selected, and those published in the last 3-5 years or in authoritative journals were preferred in the same field. Totally 89 articles were obtained in the initial retrieval, of which 53 were chosen based on the inclusion criteria. Main Outcome Measures: Biological characteristics and induced differentiation of adipose-derived stem cells and cell transplantation for disease treatment as well as the underlying mechanism of clinical application. Results: The advantages of adipose-derived stem cells include their ease of procurement, wide availability, rapid expansion, low tumorigenesis, low immunogenicity, and absence of ethical constraints. Preclinical experiments have demonstrated that transplanted adipose-derived stem cells can improve neurological functions, reduce small regions of cerebral infarction, promote angiogenesis, and express neuron-specific markers. The improvement of neurological functions was demonstrated in experiments using different methods and time courses of adipose-derived stem cell transplantation, but the mechanisms remain unclear. Conclusion: Further research into the treatment of ischemic disease by adipose-derived stem cell transplantation is needed to determine their mechanism of action. Research Highlights Adipose-derived stem cells (ADSCs) are ideal candidates for neural stem cell transplantation. This study summarizes studies on ADSCs transplantation for cerebral ischemia with respect to the biological characteristics of ADSCs, the expression of surface antigens by ADSCs, the differentiation of ADSCs into nerve cells, stereotaxic heterogenic transplantation of ADSCs, heterogenic intravenous transplantation of ADSCs, and allogeneic intravenous transplantation of ADSCs. The transplantation of ADSC-conditioned medium for the treatment of cerebrovascular disease is also discussed. Abbreviations ADSCs, adipose-derived stem cells; MSCs, mesenchymal stem cells; EGF, epidermal growth factor; FGF, fibroblast growth factor; MCAO: middle cerebral artery occlusion