Dopaminergic-like cells from epigenetically reprogrammed mesenchymal stem cells.
A number of recent studies have examined the ability of stem cells derived from different sources to differentiate into dopamine-producing cells and ameliorate behavioural deficits in Parkinsonian models. Recently, using the approach of cell reprogramming by small cell-permeable biological active compounds that involved in the regulation of chromatin structure and function, and interfere with specific cell signalling pathways that promote neural differentiation we have been able to generate neural-like cells from human bone marrow (BM)-derived MSCs (hMSCs). Neurally induced hMSCs (NI-hMSCs) exhibited several neural properties and exerted beneficial therapeutic effect on tissue preservation and locomotor recovery in spinal cord injured rats. In this study, we aimed to determine whether hMSCs neuralized by this approach can generate dopaminergic (DA) neurons. Immunocytochemisty studies showed that approximately 50-60% of NI-hMSCs expressed early and late dopaminergic marker such as Nurr-1 and TH that was confirmed by Western blot. ELISA studies showed that NI-hMSCs also secreted neurotrophins and dopamine. Hypoxia preconditioning prior to neural induction increased hMSCs proliferation, viability, expression TH and the secretion level of dopamine induced by ATP. Taken together, these studies demonstrated that hMSCs neurally modified by this original approach can be differentiated towards DA-like neurons.
Department of Neurosurgery, Neuroscience Research Labs, Medical College of Wisconsin, VAMC, Milwaukee, WI 53295, USA.
Zhiying
Z
Zhang
Arshak R
AR
Alexanian
D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000502:physiology*; D044127:Epigenesis, Genetic; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C579455:BDNF protein, human