Extrinsic modulation of integrin α6 and progenitor cell behavior in mesenchymal stem cells
Nieto-Nicolau, Núria (Institut d'Investigació Biomèdica Sant Pau)
de la Torre, Raquel M. (Universitat de Barcelona. Centres Científics i Tecnològics)
Fariñas-Balaguer, Oscar (Institut d'Investigació Biomèdica Sant Pau)
Savio, Andrés (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Vilarrodona, Anna (Institut d'Investigació Biomèdica Sant Pau)
Casaroli-Marano, Ricardo Pedro (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	Mesenchymal stem cells (MSC) are heterogeneous cells of complex nature that show different potentials while different culture conditions can modify their functionalities through interactions with the microenviroment. Here, we found that bone marrow (BM) MSC from different donor sources and passages that expressed higher levels of α6 integrin subunit (ITGA6), showed higher clonogenicity, migration and differentiation potential. ITGA6 showed important roles improving these potentials and regulating proliferation through protein kinase B (AKT) pathway and cell cycle inhibitor proteins p53 and p21. Moreover, ITGA6 downregulation impaired migration. Cell confluence regulated ITGA6, increasing its expression in low density cultures and decreasing in high density cultures. Besides, ITGA6- cells expressed ITGA6 when seeded at low densities. We found higher ITGA6 expression on fibronectin substrates at lower confluency. Fibronectin increased proliferation, clonogenicity, activation of AKT, decreased cell cycle inhibitor proteins and augmented growth factors expression. Spheres-derived MSC showed higher ITGA6 expression and enhanced potentials for migration, clonogenicity and proliferation. In conclusion, though there is an intrinsic regulation of ITGA6 expression, associated to the progenitor potential of BM-MSC, this expression is regulated by culture conditions and is translated in changes in cell behavior and proliferation. This knowledge could be used to enhance the potential of BM-MSC for clinical application.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Clonogenicity ; Integrin alpha 6 ; Mesenchymal stem cells ; Migration ; Proliferation ; Protein kinase B
Published in:	Stem Cell Research, Vol. 47 (august 2020) , p. 101899, ISSN 1876-7753

DOI: 10.1016/j.scr.2020.101899
PMID: 32659733

13 p, 5.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles