To understand the process of neurogenesis, generation of functional dopaminergic (DAergic) neurons from human mesenchymal stem cells (hMSCs) is important. BDNF has been reported to be responsible for inducing neuronal maturation and functionality. Previously, we have reported the efficient generation of neurons from human bone marrow derived MSCs using FGF2 alone. We hypothesize that hMSCs from various tissues [(bone marrow (BM), adipose tissue (AD) and dental pulp (DP)], if treated with BDNF on 9th day of induction, alongwith FGF2 will generate functional DAergic neurons. Hence, cells were characterized at morphometric, transcription and translational levels for various markers like MAP2, TH, NGN2, PITX3, DAT, synaptophysin, Kv4.2 and SCN5A. Functionality of in vitro generated neurons was studied by calcium ion imaging. Result analysis depicted that BDNF has effect on expression of dopaminergic neuronal markers at gene and protein levels and functionality of neurons. Among these hMSCs, DP-MSC showed significantly better neuronal characteristics in terms of morphology, expression of neuronal markers and foremost, functionality of neurons. From the present study, therefore, we concluded that i) BDNF has additive effect on neuronal characteristics and functionality ii) DP-MSC are better MSC candidate to study DAergic neurogenesis and perform future studies.
Clinical trials using human Mesenchymal Stem Cells (MSCs) have shown promising results in the treatment of various diseases. Different tissue sources, such as bone marrow, adipose tissue, dental pulp and umbilical cord, are being routinely used in regenerative medicine. MSCs are known to reduce increased oxidative stress levels in pathophysiological conditions. Differences in the ability of MSCs from different donors and tissues to ameliorate oxidative damage have not been reported yet. In this study, for the first time, we investigated the differences in the reactive oxygen species (ROS) reduction abilities of tissue-specific MSCs to mitigate cellular damage in oxidative stress. Hepatic Stellate cells (LX-2) and cardiomyocytes were treated with Antimycin A (AMA) to induce oxidative stress and tissue specific MSCs were co-cultured to study the reduction in ROS levels. We found that both donor's age and source of tissue affected the ability of MSCs to reduce increased ROS levels in damaged cells. In addition, the abilities of same MSCs differed in LX-2 and cardiomyocytes in terms of magnitude of reduction of ROS, suggesting that the type of recipient cells should be kept in consideration when using MSCs in regenerative medicine for treatment purposes.
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