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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.


Effect of Ad-MSC co-infusion in the homing of transplanted HSCs in the recipients’ organs. Two, four, and 24 hours after the infusion of DiD+ LSK cells, the number present in a bone marrow, b peripheral blood, c spleen, and d lungs of recipient mice was determined. The figure represents the proportion of the infused DiD+ LSK cells detected in each organ. White bars, mice infused with LSK cells. Grey bars, mice co-infused with LSK cells and Ad-MSCs. Bars represent standard error of the mean. *P ≤ 0.05. Ad-MSC adipose tissue-derived mesenchymal stem cell, HSC hematopoietic stem cell, LSK lineage− Sca-1+ cKit+, ns non-significant difference
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Fig5: Effect of Ad-MSC co-infusion in the homing of transplanted HSCs in the recipients’ organs. Two, four, and 24 hours after the infusion of DiD+ LSK cells, the number present in a bone marrow, b peripheral blood, c spleen, and d lungs of recipient mice was determined. The figure represents the proportion of the infused DiD+ LSK cells detected in each organ. White bars, mice infused with LSK cells. Grey bars, mice co-infused with LSK cells and Ad-MSCs. Bars represent standard error of the mean. *P ≤ 0.05. Ad-MSC adipose tissue-derived mesenchymal stem cell, HSC hematopoietic stem cell, LSK lineage− Sca-1+ cKit+, ns non-significant difference

Mentions: Interestingly, Ad-MSC co-infusion significantly increased the homing of LSK cells in recipients’ BM at all investigated time points (2, 4, and 24 h) (Fig. 5a). Neither in PB (Fig. 5b) nor in the spleen (Fig. 5c) did Ad-MSC co-infusion modify the presence of LSK cells in these tissues. However, at 24 h post-transplantation, increased numbers of donor LSK cells were observed in the lung of recipients that had been transplanted with Ad-MSCs (Fig. 5d), indicating that the increased homing of LSK cells in BM was not due to a decreased trapping of these cells in the lung.Fig. 5


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)

Effect of Ad-MSC co-infusion in the homing of transplanted HSCs in the recipients’ organs. Two, four, and 24 hours after the infusion of DiD+ LSK cells, the number present in a bone marrow, b peripheral blood, c spleen, and d lungs of recipient mice was determined. The figure represents the proportion of the infused DiD+ LSK cells detected in each organ. White bars, mice infused with LSK cells. Grey bars, mice co-infused with LSK cells and Ad-MSCs. Bars represent standard error of the mean. *P ≤ 0.05. Ad-MSC adipose tissue-derived mesenchymal stem cell, HSC hematopoietic stem cell, LSK lineage− Sca-1+ cKit+, ns non-significant difference
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Effect of Ad-MSC co-infusion in the homing of transplanted HSCs in the recipients’ organs. Two, four, and 24 hours after the infusion of DiD+ LSK cells, the number present in a bone marrow, b peripheral blood, c spleen, and d lungs of recipient mice was determined. The figure represents the proportion of the infused DiD+ LSK cells detected in each organ. White bars, mice infused with LSK cells. Grey bars, mice co-infused with LSK cells and Ad-MSCs. Bars represent standard error of the mean. *P ≤ 0.05. Ad-MSC adipose tissue-derived mesenchymal stem cell, HSC hematopoietic stem cell, LSK lineage− Sca-1+ cKit+, ns non-significant difference
Mentions: Interestingly, Ad-MSC co-infusion significantly increased the homing of LSK cells in recipients’ BM at all investigated time points (2, 4, and 24 h) (Fig. 5a). Neither in PB (Fig. 5b) nor in the spleen (Fig. 5c) did Ad-MSC co-infusion modify the presence of LSK cells in these tissues. However, at 24 h post-transplantation, increased numbers of donor LSK cells were observed in the lung of recipients that had been transplanted with Ad-MSCs (Fig. 5d), indicating that the increased homing of LSK cells in BM was not due to a decreased trapping of these cells in the lung.Fig. 5

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.