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Co-administration of human MSC overexpressing HIF-1α increases human CD34+ cell engraftment in vivo

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Co-administration of human MSC overexpressing HIF-1α increases human CD34+ cell engraftment in vivo

dc.contributor.author	Preciado, Silvia
dc.contributor.author	Sirerol-Piquer, M. Salomé
dc.contributor.author	Muntión, Sandra
dc.contributor.author	Osugui, Lika
dc.contributor.author	Martí-Chillón, Gerardo J.
dc.contributor.author	Navarro-Bailón, Almudena
dc.contributor.author	Sepúlveda, Pilar
dc.contributor.author	Sánchez-Guijo, Fermín
dc.date.accessioned	2022-04-04T13:14:51Z
dc.date.available	2022-04-04T13:14:51Z
dc.date.issued	2021
dc.identifier.citation	Preciado, Silvia Sirerol-Piquer, M. Salomé Muntión, Sandra Osugui, Lika Martí-Chillón, Gerardo J. Navarro-Bailón, Almudena Sepúlveda, Pilar Sánchez-Guijo, Fermín 2021 Co-administration of human MSC overexpressing HIF-1α increases human CD34+ cell engraftment in vivo Stem Cell Research & Therapy 12 601 1 12
dc.identifier.uri	https://hdl.handle.net/10550/82147
dc.description.abstract	Background: Poor graft function or graft failure after allogeneic stem cell transplantation is an unmet medical need, in which mesenchymal stromal cells (MSC) constitute an attractive potential therapeutic approach. Hypoxia-inducible factor-1α (HIF-1α) overexpression in MSC (HIF-MSC) potentiates the angiogenic and immunomodulatory properties of these cells, so we hypothesized that co-transplantation of MSC-HIF with CD34+ human cord blood cells would also enhance hematopoietic stem cell engraftment and function both in vitro and in vivo. Methods: Human MSC were obtained from dental pulp. Lentiviral overexpression of HIF-1α was performed transducing cells with pWPI-green fluorescent protein (GFP) (MSC WT) or pWPI-HIF-1α-GFP (HIF-MSC) expression vectors. Human cord blood CD34+ cells were co-cultured with MSC WT or HIF-MSC (4:1) for 72 h. Then, viability (Annexin V and 7-AAD), cell cycle, ROS expression and immunophenotyping of key molecules involved in engraftment (CXCR4, CD34, ITGA4, c-KIT) were evaluated by flow cytometry in CD34+ cells. In addition, CD34+ cells clonal expansion was analyzed by clonogenic assays. Finally, in vivo engraftment was measured by flow cytometry 4-weeks after CD34+ cell transplantation with or without intrabone MSC WT or HIF-MSC in NOD/SCID mice. Results: We did not observe significant differences in viability, cell cycle and ROS expression between CD34+ cells co-cultured with MSC WT or HIF-MSC. Nevertheless, a significant increase in CD34, CXCR4 and ITGA4 expression (p = 0.009; p = 0.001; p = 0.013, respectively) was observed in CD34+ cells co-cultured with HIF-MSC compared to MSC WT. In addition, CD34+ cells cultured with HIF-MSC displayed a higher CFU-GM clonogenic potential than those cultured with MSC WT (p = 0.048). We also observed a significant increase in CD34+ cells engraftment ability when they were co-transplanted with HIF-MSC compared to CD34+ co-transplanted with MSC WT (p = 0.016) or alone (p = 0.015) in both the injected and contralateral femurs (p = 0.024, p = 0.008 respectively). Conclusions: Co-transplantation of human CD34+ cells with HIF-MSC enhances cell engraftment in vivo. This is probably due to the ability of HIF-MSC to increase clonogenic capacity of hematopoietic cells and to induce the expression of adhesion molecules involved in graft survival in the hematopoietic niche.
dc.language.iso	eng
dc.relation.ispartof	Stem Cell Research & Therapy, 2021, vol. 12, num. 601, p. 1-12
dc.subject	Cèl·lules mare
dc.subject	Trasplantació d'òrgans, teixits, etc.
dc.title	Co-administration of human MSC overexpressing HIF-1α increases human CD34+ cell engraftment in vivo
dc.type	journal article	es_ES
dc.date.updated	2022-04-04T13:14:52Z
dc.identifier.doi	10.1186/s13287-021-02669-z
dc.identifier.idgrec	151122
dc.rights.accessRights	open access	es_ES