Extrinsic modulation of integrin alpha 6 and progenitor cell behavior in mesenchymal stem cells
Por:
Nieto-Nicolau, N, de la Torre, RM, Farinas, O, Savio, A, Vilarrodona, A, Casaroli-Marano, RP
Publicada:
1 ago 2020
Resumen:
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 alpha 6 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, ITGA6cells 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.
Filiaciones:
Nieto-Nicolau, N:
Barcelona Tissue Bank BTB, Barcelona, Spain
Banc Sang & Teixits BST, Donor Ctr, Barcelona, Spain
Univ Barcelona, CellTec UB, Barcelona, Spain
Inst Biomed Res St Pau IIB St Pau, Barcelona, Spain
de la Torre, RM:
Univ Barcelona, CellTec UB, Barcelona, Spain
Farinas, O:
Barcelona Tissue Bank BTB, Barcelona, Spain
Banc Sang & Teixits BST, Donor Ctr, Barcelona, Spain
Inst Biomed Res St Pau IIB St Pau, Barcelona, Spain
Savio, A:
Barcelona Tissue Bank BTB, Barcelona, Spain
Banc Sang & Teixits BST, Donor Ctr, Barcelona, Spain
Inst Biomed Res St Pau IIB St Pau, Barcelona, Spain
Vilarrodona, A:
Barcelona Tissue Bank BTB, Barcelona, Spain
Banc Sang & Teixits BST, Donor Ctr, Barcelona, Spain
Inst Biomed Res St Pau IIB St Pau, Barcelona, Spain
Casaroli-Marano, RP:
Barcelona Tissue Bank BTB, Barcelona, Spain
Banc Sang & Teixits BST, Donor Ctr, Barcelona, Spain
Univ Barcelona, CellTec UB, Barcelona, Spain
Univ Barcelona, Sch Med, Dept Surg, Calle Sabino de Arana 1,2nd Floor Ophthalmol, E-08028 Barcelona, Spain
Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain
Inst Biomed Res St Pau IIB St Pau, Barcelona, Spain
Green Published, gold
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