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Mesenchymal stromal cells enhance the engraftment of hematopoietic stem cells in an autologous mouse transplantation model.

Fernández-García M, Yañez RM, Sánchez-Domínguez R, Hernando-Rodriguez M, Peces-Barba M, Herrera G, O'Connor JE, Segovia JC, Bueren JA, Lamana ML - Stem Cell Res Ther (2015)

Bottom Line: This effect was Ad-MSC dose-dependent and associated with an increased homing of transplanted HSCs in recipients' bone marrow.In vivo and in vitro experiments also indicate that the Ad-MSC effects observed in this autologous transplant model are not due to paracrine effects but rather are related to Ad-MSC and HSC interactions, allowing us to propose that Ad-MSCs may act as HSC carriers, facilitating the migration and homing of the HSCs to recipient bone marrow niches.Our results demonstrate that Ad-MSCs facilitate the engraftment of purified HSCs in an autologous mouse transplantation model, opening new perspectives in the application of Ad-MSCs in autologous transplants, including HSC gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Hematopoietic Innovative Therapies Division. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER), Madrid, Spain. maria.fernandez@ciemat.es.

ABSTRACT

Introduction: Studies have proposed that mesenchymal stem cells (MSCs) improve the hematopoietic engraftment in allogeneic or xenogeneic transplants and this is probably due to the MSCs' immunosuppressive properties. Our study aimed to discern, for the first time, whether MSC infusion could facilitate the engraftment of hematopoietic stem cells (HSCs) in autologous transplantations models, where no immune rejection of donor HSCs is expected.

Methods: Recipient mice (CD45.2) mice, conditioned with moderate doses of radiation (5-7 Gy), were transplanted with low numbers of HSCs (CD45.1/CD45.2) either as a sole population or co-infused with increasing numbers of adipose-derived-MSCs (Ad-MSCs). The influence of Ad-MSC infusion on the short-term and long-term engraftment of donor HSCs was investigated. Additionally, homing assays and studies related with the administration route and with the Ad-MSC/HSC interaction were conducted.

Results: Our data show that the co-infusion of Ad-MSCs with low numbers of purified HSCs significantly improves the short-term and long-term hematopoietic reconstitution of recipients conditioned with moderate irradiation doses. This effect was Ad-MSC dose-dependent and associated with an increased homing of transplanted HSCs in recipients' bone marrow. In vivo and in vitro experiments also indicate that the Ad-MSC effects observed in this autologous transplant model are not due to paracrine effects but rather are related to Ad-MSC and HSC interactions, allowing us to propose that Ad-MSCs may act as HSC carriers, facilitating the migration and homing of the HSCs to recipient bone marrow niches.

Conclusion: Our results demonstrate that Ad-MSCs facilitate the engraftment of purified HSCs in an autologous mouse transplantation model, opening new perspectives in the application of Ad-MSCs in autologous transplants, including HSC gene therapy.

No MeSH data available.


Mouse Ad-MSC characterization. a Ad-MSCs’ fibroblast-like morphology. b Osteogenic differentiation. c Adipogenic differentiation. d Ad-MSC immunophenotype, negative for hematopoietic markers CD34, CD45.1, CD80, and low Sca-1 and positive for CD29, CD44, CD73, CD90.2, CD105, CD106, CD144, and CD166 expression. Ad-MSC adipose tissue-derived mesenchymal stem cell
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Fig1: Mouse Ad-MSC characterization. a Ad-MSCs’ fibroblast-like morphology. b Osteogenic differentiation. c Adipogenic differentiation. d Ad-MSC immunophenotype, negative for hematopoietic markers CD34, CD45.1, CD80, and low Sca-1 and positive for CD29, CD44, CD73, CD90.2, CD105, CD106, CD144, and CD166 expression. Ad-MSC adipose tissue-derived mesenchymal stem cell

Mentions: In the current studies, MSCs obtained from adipose tissue (Ad-MSCs) were used throughout. Consistent with our previous studies, Ad-MSCs showed the characteristic fibroblast-like morphology (Fig. 1a), had osteogenic and adipogenic differentiation capacity (Fig. 1b, c), and were negative for hematopoietic marker expression and positive for CD29, CD44, CD73, CD90.2, CD105, CD106, CD144, and CD166 expression (Fig. 1d).Fig. 1


Mesenchymal stromal cells enhance the engraftment of hematopoietic stem cells in an autologous mouse transplantation model.

Fernández-García M, Yañez RM, Sánchez-Domínguez R, Hernando-Rodriguez M, Peces-Barba M, Herrera G, O'Connor JE, Segovia JC, Bueren JA, Lamana ML - Stem Cell Res Ther (2015)

Mouse Ad-MSC characterization. a Ad-MSCs’ fibroblast-like morphology. b Osteogenic differentiation. c Adipogenic differentiation. d Ad-MSC immunophenotype, negative for hematopoietic markers CD34, CD45.1, CD80, and low Sca-1 and positive for CD29, CD44, CD73, CD90.2, CD105, CD106, CD144, and CD166 expression. Ad-MSC adipose tissue-derived mesenchymal stem cell
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4562358&req=5

Fig1: Mouse Ad-MSC characterization. a Ad-MSCs’ fibroblast-like morphology. b Osteogenic differentiation. c Adipogenic differentiation. d Ad-MSC immunophenotype, negative for hematopoietic markers CD34, CD45.1, CD80, and low Sca-1 and positive for CD29, CD44, CD73, CD90.2, CD105, CD106, CD144, and CD166 expression. Ad-MSC adipose tissue-derived mesenchymal stem cell
Mentions: In the current studies, MSCs obtained from adipose tissue (Ad-MSCs) were used throughout. Consistent with our previous studies, Ad-MSCs showed the characteristic fibroblast-like morphology (Fig. 1a), had osteogenic and adipogenic differentiation capacity (Fig. 1b, c), and were negative for hematopoietic marker expression and positive for CD29, CD44, CD73, CD90.2, CD105, CD106, CD144, and CD166 expression (Fig. 1d).Fig. 1

Bottom Line: This effect was Ad-MSC dose-dependent and associated with an increased homing of transplanted HSCs in recipients' bone marrow.In vivo and in vitro experiments also indicate that the Ad-MSC effects observed in this autologous transplant model are not due to paracrine effects but rather are related to Ad-MSC and HSC interactions, allowing us to propose that Ad-MSCs may act as HSC carriers, facilitating the migration and homing of the HSCs to recipient bone marrow niches.Our results demonstrate that Ad-MSCs facilitate the engraftment of purified HSCs in an autologous mouse transplantation model, opening new perspectives in the application of Ad-MSCs in autologous transplants, including HSC gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Hematopoietic Innovative Therapies Division. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER), Madrid, Spain. maria.fernandez@ciemat.es.

ABSTRACT

Introduction: Studies have proposed that mesenchymal stem cells (MSCs) improve the hematopoietic engraftment in allogeneic or xenogeneic transplants and this is probably due to the MSCs' immunosuppressive properties. Our study aimed to discern, for the first time, whether MSC infusion could facilitate the engraftment of hematopoietic stem cells (HSCs) in autologous transplantations models, where no immune rejection of donor HSCs is expected.

Methods: Recipient mice (CD45.2) mice, conditioned with moderate doses of radiation (5-7 Gy), were transplanted with low numbers of HSCs (CD45.1/CD45.2) either as a sole population or co-infused with increasing numbers of adipose-derived-MSCs (Ad-MSCs). The influence of Ad-MSC infusion on the short-term and long-term engraftment of donor HSCs was investigated. Additionally, homing assays and studies related with the administration route and with the Ad-MSC/HSC interaction were conducted.

Results: Our data show that the co-infusion of Ad-MSCs with low numbers of purified HSCs significantly improves the short-term and long-term hematopoietic reconstitution of recipients conditioned with moderate irradiation doses. This effect was Ad-MSC dose-dependent and associated with an increased homing of transplanted HSCs in recipients' bone marrow. In vivo and in vitro experiments also indicate that the Ad-MSC effects observed in this autologous transplant model are not due to paracrine effects but rather are related to Ad-MSC and HSC interactions, allowing us to propose that Ad-MSCs may act as HSC carriers, facilitating the migration and homing of the HSCs to recipient bone marrow niches.

Conclusion: Our results demonstrate that Ad-MSCs facilitate the engraftment of purified HSCs in an autologous mouse transplantation model, opening new perspectives in the application of Ad-MSCs in autologous transplants, including HSC gene therapy.

No MeSH data available.