title: Dopaminergic-primed fetal liver mesenchymal stromal-like cells can reverse parkinsonian symptoms in 6-hydroxydopamine-lesioned mice.
abstract: OBJECTIVE
  Cell replacement therapy is considered a promising alternative in the treatment of degenerative diseases, and in this context, mesenchymal stromal cells (MSCs) have been proposed for transplantation in Parkinson disease (PD). Thus far, the results of animal studies are found to be inconsistent and inconclusive regarding the therapeutic ability of the cells. This study investigated the efficacy of fetal liver (FL)-MSC-derived dopaminergic (DA) neuronal primed cells for correction of parkinsonian symptoms in mice.
  
  
  METHODS
  FL-MSCs were differentiated for 21 days in the presence of a combination of neurotropic factors. The extent of cellular reprogramming was analyzed by quantitative polymerase chain reaction for DA-specific neuronal gene expressions and protein expressions by immuno-cytochemistry. The functionality of the cells was determined by electrophysiology and dopamine release assays. Ten-day-primed neuron-like cells or unprimed MSCs were transplanted into the 6-hydroxydopamine (6-OHDA)-lesioned striatum using a stereotaxic device. Dopamine-secreting properties and behavioral studies were used to assess improvement of parkinsonian symptoms.
  
  
  RESULTS
  The differentiated cells expressed DA-specific genes and proteins, while exhibiting a high level of voltage-gated potassium current. Furthermore, neuronal primed cells differentiated into tyrosine hydroxylase immunoreactive and dopamine-secreting functional neuron-like cells. Symptomatic correction of PD in the recipient mice within 2 months of transplantation was also observed.
  
  
  CONCLUSIONS
  FL-MSC-derived primed neuron-like cells integrated into the striatum of PD mice, improving parkinsonian symptoms. This study demonstrates an effective cell-based therapy for PD.
authors: Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors: Amit
authors: A
authors: Kumar
authors: Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors: Swati
authors: S
authors: Dudhal
authors: Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors: Abinaya
authors: A
authors: Sundari T
authors: Daiichi Sankyo India Pharma Pvt Ltd, Village Sarhaul, Gurgaon, India.
authors: Mallikarjuna
authors: M
authors: Sunkara
authors: Daiichi Sankyo India Pharma Pvt Ltd, Village Sarhaul, Gurgaon, India.
authors: Hyder
authors: H
authors: Usman
authors: Daiichi Sankyo India Pharma Pvt Ltd, Village Sarhaul, Gurgaon, India.
authors: Anurag
authors: A
authors: Varshney
authors: Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India. Electronic address: ashok@nii.ac.in.
authors: Asok
authors: A
authors: Mukhopadhyay
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D005333:Fetus / Q000166:cytology*; D008099:Liver / Q000187:drug effects / Q000196:embryology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D011247:Pregnancy; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: 6-OHDA; Apomorphine-induced rotation; Differentiation; Dopamine secretion; Dopaminergic neurons; Fetal liver MSCs; Parkinson disease