Vaidya, A. and Singh, S. and Limaye, L. and Kale, V. (2019) Chimeric feeders of mesenchymal stromal cells and stromal cells modified with constitutively active AKT expandhematopoietic stem cells. Regenerative Medicine, 14 (6). pp. 535-553.

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Abstract

Aim: To examine whether AKT-modified stromal cells expand human CD34+ hematopoietic stem cells (HSCs). Methods: Coculture, in vitro functional assays, immuno-fluorescence microscopy, flow cytometry. Results: M2-10B4 stromal cells (M2) modified with AKT1 (M2-AKT) expanded primitive CD34+38- HSCs, but affected their functionality. A chimeric feeder layer comprising naive human bone marrow-derived mesenchymal stromal cells and M2-AKT not only overcame the negative effects of M2-AKT, but, unexpectedly, also gave a synergistic effect on the growth and functionality of the HSCs. Conditioned medium of bone marrow stromal cells worked as effectively, but cell–cell contact between HSCs and M2-AKT cells was necessary for the synergistic effect of M2-AKT and bone marrow-derived mesenchymal stromal cells or their CM. Conclusion: Chimeric feeders expand HSCs. Graphical abstract showing the effect of various stromal cells on the growth and functionality of human CD34+ hematopoietic stem cells (HSCs): Stromal cells having a constitutively active AKT expand HSCs, but severely affect their functionality. Naive bone marrow-derived stromal cells support a limited expansion of functional HSCs. On the other hand, a combination of stromal cells having a constitutively active AKT and naive stromal cells or their conditioned medium exerts a synergistic effect on growth and functionality of the HSCs.

Item Type:	Article
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	21 Feb 2020 04:18
Last Modified:	21 Feb 2020 04:18
URI:	http://nccs.sciencecentral.in/id/eprint/726

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