Publications (2)4.21 Total impact
-
Article: Transplants of Human Mesenchymal Stem Cells Improve Functional Recovery After Spinal Cord Injury in the Rat
[show abstract] [hide abstract]
ABSTRACT: Human mesenchymal stem cells (hMSCs) derived from adult bone marrow represent a potentially useful source of cells for cell replacement therapy after nervous tissue damage. They can be expanded in culture and reintroduced into patients as autografts or allografts with unique immunologic properties. The aim of the present study was to investigate (i) survival, migration, differentiation properties of hMSCs transplanted into non-immunosuppressed rats after spinal cord injury (SCI) and (ii) impact of hMSC transplantation on functional recovery. Seven days after SCI, rats received i.v. injection of hMSCs (2×106 in 0.5mL DMEM) isolated from adult healthy donors. Functional recovery was assessed by Basso–Beattie–Bresnahan (BBB) score weekly for 28 days. Our results showed gradual improvement of locomotor function in transplanted rats with statistically significant differences at 21 and 28 days. Immunocytochemical analysis using human nuclei (NUMA) and BrdU antibodies confirmed survival and migration of hMSCs into the injury site. Transplanted cells were found to infiltrate mainly into the ventrolateral white matter tracts, spreading also to adjacent segments located rostro-caudaly to the injury epicenter. In double-stained preparations, hMSCs were found to differentiate into oligodendrocytes (APC), but not into cells expressing neuronal markers (NeuN). Accumulation of GAP-43 regrowing axons within damaged white matter tracts after transplantation was observed. Our findings indicate that hMSCs may facilitate recovery from spinal cord injury by remyelinating spared white matter tracts and/or by enhancing axonal growth. In addition, low immunogenicity of hMSCs was confirmed by survival of donor cells without immunosuppressive treatment.Cellular and Molecular Neurobiology 04/2012; 26(7):1165-1178. · 1.97 Impact Factor -
Article: Induction of Mesenchymal Stem Cells Leads to HSP72 Synthesis and Higher Resistance to Oxidative Stress
[show abstract] [hide abstract]
ABSTRACT: The phenomenon of neuronal transdifferentiation performed on bone marrow mesenchymal stem cells (MSCs) has been criticized by recent studies indicating that acquired neuron-like morphology of induced MSCs is caused by cellular stress. Therefore, to test this hypothesis we have investigated whether exposure of rat MSCs (rMSCs) to chemical inducer 2mM β-mercaptoethanol (BME) for 1–3h followed by 24h incubation leads to HSP72 synthesis, thus suggesting higher resistance of rMSCs to oxidative damage. Present data from immunohistochemistry clearly indicate development of time-dependent sub-cellular HSP72 distribution, initially seen in nuclei at 1h followed by its translocation to surrounding central cytoplasm and processes at 2–3h after BME stimulation. Western blot (WB) analysis confirmed the expression of HSP72 protein in induced rMSCs at both stimulation periods. Furthermore, preconditioned rMSCs with BME for 1h expressing HSP72 positivity at 24h showed higher resistance (78±10% of survival cells) to oxidative stress caused by 1mM H2O2 when compared to those preconditioned for 3h (59±8% of survival cells) or control-unconditioned rMSCs exposed to the same stressor conditions (56±6% of survival cells). Thus, the cellular protection was lost if the duration of BME preconditioning was increased as far as possible (3h) (while still remaining sub-lethal). This suggests that exposure of rMSCs to the optimal concentration of BME (2mM) during optimal induction period (1h) mediate their protection and increases resistance to oxidative injury, while over crossing these limits is in-effective. In addition, our findings confirm that cultured rMSCs remain competent to be preconditioned by BME, through a pathway that may increase the antioxidant balance or involve activation of HSP72 protein induced tolerance.Neurochemical Research 04/2012; 31(8):1011-1020. · 2.24 Impact Factor
