Abstract
With no permanent cure for neurodegenerative diseases, the symptoms reappear shortly after the withdrawal of medicines. A better treatment outcome can be expected if the damaged neurons are partly replaced by functional neurons and/or they are repaired using trophic factors. In this regard, safe cell therapy has been considered as a potential alternative to conventional treatment. Here, we have described a two-stage culture process to differentiate Wharton Jelly mesenchymal stem cells (WJ-MSCs) into neuronal-like cells in the presence of various cues involved in neurogenesis. The fate of cells at the end of each stage was analyzed at the morphometric, transcriptional, and translational levels. In the first stage of priming, constitutively, wingless-activated WJ-MSCs crossed the lineage boundary in favor of neuroectodermal lineage, identified by the loss of mesenchymal genes with concomitant expression of neuron-specific markers, like SOX1, PAX6, NTRK1, and NEUROD2. Neuronal-like cells formed in the second stage expressed many mature neuronal proteins like Map2, neurofilament, and Tuj1 and possessed axon hillock-like structures. In conclusion, the differentiation of a large number of neuronal-like cells from nontumorigenic and trophic factors secreting WJ-MSCs promises the development of a therapeutic strategy to treat neurodegenerative diseases.
Highlights
Neurodegenerative disorders, accounting above 10% of worldwide deaths, arise due to loss or dysfunction of neurons and/or glial cells of the central nervous system [1]
Besides the analysis of a various cluster of differentiation (CD) markers as laid down by the International Society of Cellular Therapy (ISCT) in 2006 (Supplementary Figures 1A and 1B) [42], WJ-derived mesenchymal stem cells (MSCs) were analyzed for the expression of pluripotent CD markers
CD146/Melanoma cell adhesion molecule (MCAM), which acts as a receptor of laminin was found to express in 96:5 ± 1:79% of the WJMSCs, whereas, unlike BM-MSCs, Wharton’s jelly-derived MSCs (WJ-MSCs) did not show the expression of CD271 (Figure 1(a))
Summary
Neurodegenerative disorders, accounting above 10% of worldwide deaths, arise due to loss or dysfunction of neurons and/or glial cells of the central nervous system [1]. To circumvent the concerns associated with the abovementioned stem cells, the potential of mesenchymal stem cells (MSCs) for cell-based therapy is explored owing to their hypoimmunogenic, immunomodulatory, homing, nontumorogenic, and transdifferentiation properties [8, 15]. Wharton’s jelly-derived MSCs (WJ-MSCs) seem more promising with higher immunomodulatory, hypoimmunogenic, and multilineage differentiation potential, owing to their primitive origin [20]. The caveats of this potential therapy are that the paracrine effects alone may not be adequate to reverse neurodegeneration in the advanced stage of patients and the ability of MSCs to form multilineage tissues in vivo. Being immunomodulatory in nature, MSCs transplantation may suppress the host immune system [30] To circumvent these problems, it is always safe to differentiate or prime MSCs towards the neuronal lineage prior to transplantation for treating patients suffering from neurodegeneration
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