Clinical grade mesenchymal stem cells transdifferentiated under xenofree conditions alleviates motor deficiencies in a rat model of Parkinson's disease |
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Authors: | Prathibha Shetty Geeta Ravindran Shabari Sarang Anirbhan M. Thakur Harinarayana S. Rao Chandra Viswanathan |
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Affiliation: | aRegenerative Medicine, Haematopoietic Stem Cell Group;bLaboratory Animal Research Services, Reliance Life Sciences Pvt Ltd, Dhirubhai Ambani Life Sciences Centre, R-282 TTC Area of MIDC, Thane Belapur Road, Rabale, Navi Mumbai 400701, India |
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Abstract: | Bone marrow derived mesenchymal stem cells (BMMSCs) is a valid, definitive candidate for repair of damaged tissues in degenerative disorders in general and neurological diseases in particular. We have standardized the processing conditions for proliferation of BMMSCs using xenofree medium and checked their in vitro and in vivo neurogenic potential.MethodThe proliferative potential of BMMSCs was analyzed using xenofree media and functionality checked by transplantation into Parkinson's disease (PD) animal models. In vitro neuronal differentiation was investigated by neuronal induction media supplemented with growth factors. Differentiated cells were characterized at cellular and molecular levels. In vitro functionality estimated by dopamine secretion.ResultsA pure population of BMMSCs showing an 8–10 fold expansion was obtained using xenofree media. On differentiation to neuronal lineage, they exhibited neuronal morphology. Detectable levels of dopamine (1.93 ng/ml) were secreted into the culture media of differentiated cells. There was a significant behavioural improvement in PD models 3 months post transplantation.ConclusionOur study demonstrates that BMMSCs can be transdifferentiated efficiently into functional dopaminergic neurons both in vitro and in vivo. This holds immense clinical potential as a replacement therapy for PD and other neurodegenerative diseases. |
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Keywords: | Bone marrow Clinical grade mesenchymal stem cells (MSCs) Cord blood serum (CBS) Dopaminergic neurons 6-Hydroxydopamine (6-OHDA) Parkinson's disease (PD) |
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