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AD-MSCs as Neural Progenitor Cells: Insights into Differentiation Mechanisms and Signaling Pathways
Author(s):
1. Lubna Khan: Institute of Biomedical Sciences, DUHS, Karachi, Pakistan
2. Nazia Ahmed: Dow Research Institute of Biotechnology and Biomedical Sciences, DUHS, Karachi, Pakistan
3. Nadia Naeem: Dow Research Institute of Biotechnology and Biomedical Sciences, DUHS, Karachi, Pakistan
4. Sumreen Begum: Stem Cells Research Laboratory, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
5. Abdul Khalique Mahar: Dow International Medical College, DUHS, Karachi, Pakistan
6. Bushra Nadeem: Surgical Unit 4, Civil Hospital, Karachi, Pakistan
Abstract:
Regenerative medicine field provides a vast prospect for developing neural cells from different stem cell sources for cellular therapy to treat neurological disorders. Mesenchymal stem cell (MSCs) population in adipose tissue has proposed the potential to differentiate in neural cells which participate in repair and regeneration of damaged brain areas. The abundant progress has been made in discovering fundamental mechanisms of small molecules and growth factors to differentiate MSCs into a specific cell lineage. The developmental studies explained the importance of Wnt, Notch and fibroblast growth factor signaling for in vitro generation of neural precursors/progenitors. The objective of the current study was to cultivate and differentiate human adipose tissue derived MSCs (AD-MSCs) in neural progenitor cells using small molecules Valproic acid, CHIR99021 and fibroblast growth factor-9 (FGF-9). The morphological results of treated cells showed neural like cells appearance induced by VPA+FGF-9 with highest expression of neural progenitor marker nestin (P<0.001) as compared to the cells treated by VPA+CHIR+FGF-9 and CHIR+FGF-9. Furthermore, a significant increase was found in the expression levels of other neural genetic markers Choline Acetyltransferase (ChAT) and Glial fibrillary acidic protein (GFAP) in cells treated with VPA+FGF-9 (P<0.001 and P<0.05 respectively). The findings propose that Notch/FGF signaling has a potential role in neural induction of AD-MSCs in-vitro. Initial activation of notch signaling by VPA with addition of FGF-9 has generated cholinergic like neurons from AD-MSCs. However, further molecular signaling mechanism and in vivo studies will be required to confirm the potential use of these factors for neurogenesis and regeneration in future.
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Published: Journal: Abstract Book on 9th Annual Neuroscience Conference (ANC-23) August 12-13, 2023 , Volume: 0, Issue: 0, Year: 2023
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