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


CONCLUSIONS
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.
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.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. maria.fernandez@ciemat.es.
María
M
Fernández-García
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. rosamaria.yanez@ciemat.es.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. rosamaria.yanez@ciemat.es.
Rosa M
RM
Yañez
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. rebeca.sanchez@externos.ciemat.es.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. rebeca.sanchez@externos.ciemat.es.
Rebeca
R
Sánchez-Domínguez
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. miriam.hernando@externos.ciemat.es.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. miriam.hernando@externos.ciemat.es.
Miriam
M
Hernando-Rodriguez
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. mpecesbarbagomez@gmail.com.
Miguel
M
Peces-Barba
Cytometry Service. UCIM. INCLIVA-Universidad de Valencia, Avda Blasco Ibañez 13, 46010, Valencia, Spain. gherreramartin@gmail.com.
Guadalupe
G
Herrera
Laboratory of Cytomics. Universidad de Valencia, Avda Blasco Ibañez 13, 46010, Valencia, Spain. jose.e.oconnor@uv.es.
Jose E
JE
O'Connor
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. jc.segovia@ciemat.es.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. jc.segovia@ciemat.es.
José C
JC
Segovia
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. juan.bueren@ciemat.es.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. juan.bueren@ciemat.es.
Juan A
JA
Bueren
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. maruja.lamana@ciemat.es.|Unidad Mixta de Terapias Avanzadas. Instituto de Investigación Sanitaria Fundación Jiménez Díaz. (IIS-FJD, UAM), Avda Complutense 40, 28040, Madrid, Spain. maruja.lamana@ciemat.es.
María L
ML
Lamana
D000818:Animals; D002478:Cells, Cultured; D006084:Graft Rejection; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D014182:Transplantation, Autologous