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Background Human bone marrow multipotent mesenchymal stromal cells (hMSC), because of their capacity of multipotency, may provide an unlimited cell source for cell replacement therapy. The purpose of this study was to assess the developmental potential of hMSC to replace the midbrain dopamine neurons selectively lost in Parkinson's disease. Methods Cells were isolated and characterized, then induced to differentiate toward the neural lineage. In vitro analysis of neural differentiation was achieved using various methods to evaluate the expression of neural and dopaminergic genes and proteins. Neural-induced cells were then transplanted into the striata of hemi-Parkinsonian rats; animals were tested for rotational behavior and, after killing, immunohistochemistry was performed. Results Following differentiation, cells displayed neuronal morphology and were found to express neural genes and proteins. Furthermore, some of the cells exhibited gene and protein profiles typical of dopaminergic precursors. Finally, transplantation of neural-induced cells into the striatum of hemi-Parkinsonian rats resulted in improvement of their behavioral deficits, as determined by apomorphine-induced rotational behavior. The transplanted induced cells proved to be of superior benefit compared with the transplantation of naive hMSC. Immunohistochemical analysis of grafted brains revealed that abundant induced cells survived the grafts and some displayed dopaminergic traits. Discussion Our results demonstrate that induced neural hMSC may serve as a new cell source for the treatment of neurodegenerative diseases and have potential for broad application. These results encourage further developments of the possible use of hMSC in the treatment of Parkinson's disease.

Mesenchymal stromal cells (MSC) may be useful in a range of clinical applications. The placenta has been suggested as an abundant, ethically acceptable, less immunogenic and easily accessible source of MSC. The aim of this study was to evaluate the capacity of induced placental MSC to differentiate into neurotrophic factor-producing cells (NTF) and their protective effect on neuronal cells.MSC were isolated from placentas and characterized by fluorescence-activated cell sorting (FACS). The cells underwent an induction protocol to differentiate them into NTF. Analysis of the cellular differentiation was done using polymerase chain reactions (PCR), immunocytochemical staining and enzyme-linked immunosorbent assays (ELISA). Conditioned media from placental MSC (PL-MSC) and differentiated MSC (PL-DIFF) were collected and examined for their ability to protect neural cells.The immunocytochemical studies showed that the cells displayed typical MSC membrane markers. The cells differentiated into osteoblasts and adipocytes. PCR and immunohistology staining demonstrated that the induced cells expressed typical astrocytes markers and neurotrophic factors. Vascular endothelial growth factor (VEGF) levels were higher in the conditioned media from PL-DIFF compared with PL-MSC, as indicated by ELISA. Both PL-DIFF and PL-MSC conditioned media markedly protected neural cells from oxidative stress induced by H(2)O(2) and 6-hydroxydopamine. PL-DIFF conditioned medium had a superior effect on neuronal cell survival. Anti-VEGF antibodies (Bevacizumab) reduced the protective effect of the conditioned media from differentiated and undifferentiated MSC.This study has demonstrated a neuroprotective effect of MSC of placental origin subjected to an induction differentiation protocol. These data offer the prospect of using placenta as a source for stem cell-based therapies.

Background aims Bone marrow (BM) multipotent mesenchymal stromal cells (MSC) hold great potential for cell-based regenerative medicine. Because of the growing use of autologous rat MSC transplantation in various rat models, there is a need to establish minimal criteria for rat MSC characterization independent of the specific strain employed in each study. We aimed to compare the phenotypic and functional traits of BM MSC from the four strains of rats commonly used in research: Fisher, Lewis, SpragueDawley and Wistar. Methods Rat MSC were isolated from the BM of the four different rat strains in an identical fashion. Cells were characterized for their cell-surface phenotype in early and late passage. Functional mesenchymal differentiation capacities were examined following adipogenic and osteogenic inductions. Population doubling times were determined across the four strains throughout 10 passages. In vitro proliferation assays of immune cells were conducted following co-culture of spleen cells and MSC of the four different strains. Results We found that rat MSC from different strains exhibited similar cellsurface phenotype. Expansion rates and differentiation capacities of the MSC were also similar across the different strains. Co-culture of rat MSC with spleen cells obtained from rats of a different strain did not induce proliferation of immune cells. Conclusions Our findings suggest that BM-derived MSC from different strains share similar characteristics, in contrast to the variations previously described in the characterization of mice MSC from different strains.