Clinical grade mesenchymal stem cells transdifferentiated under xenofree conditions alleviates motor deficiencies in a rat model of Parkinson's disease.
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.


METHODS
The 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.


RESULTS
A 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.


CONCLUSIONS
Our 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.
Shetty
Prathibha
P
Regenerative Medicine, Haematopoietic Stem Cell Group, Dhirubhai Ambani Life Sciences Centre, R-282 TTC Area of MIDC, Thane Belapur Road, Rabale, Navi Mumbai 400701, India. prathibha_shetty@relbio.com
Ravindran
Geeta
G
Sarang
Shabari
S
Thakur
Anirbhan M
AM
Rao
Harinarayana S
HS
Viswanathan
Chandra
C
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
D015415:Biomarkers; D004298:Dopamine