How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models

BACKGROUND Bone marrow transplantation(BMT)can be applied to both hematopoietic and nonhematopoietic diseases;nonetheless,it still comes with a number of challenges and limitations that contribute to treatment failure.Bearing this in mind,a possible way to increase the success rate of BMT would be cotransplantation of mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs)to improve the bone marrow niche and secrete molecules that enhance the hematopoietic engraftment.AIM To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models.METHODS We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment.We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English.In PubMed,we initially identified 555 articles and after selection,only 12 were chosen.In Scopus,2010 were identified,and six were left after the screening and eligibility process.RESULTS Of the 2565 articles found in the databases,only 18 original studies met the eligibility criteria.HSC distribution by source showed similar ratios,with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1×10^(7) cells by intravenous or intrabone routes.However,MSCs had a high prevalence of human donors with a variety of sources(umbilical cord blood,bone marrow,tonsil,adipose tissue or fetal lung),using a lower dose,mainly 106 cells and ranging 104 to 1.5×107 cells,utilizing the same routes.MSCs were characterized prior to administration in almost every experiment.The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy.The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism,followed by hematopoietic reconstitution and survival analysis.Besides the engraftment,homing and cellularity were also evaluated in some studies.CONCLUSION The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models,in the absence of toxicity.

Immune privilege induced by cotransplantation of islet and allogeneic testicular cells

Objective To induce islet allograft long-term survival through cotransplantation of islet cells with sertoli cells.Methods Testicular sertoli cells were prepared by digestion with collagenase, trypsin and DNase, and were cultured for 48 hours. Collagenase digested and Ficoll purified donor (Wistar rat) islets were cotransplanted with allogeneic sertoli cells in the absence of systemic immunosuppression. Terminal leoxynucleotidyl transferase-mediated X-dUTP nick-end labeling (TUNEL) was used to label apoptosis of lymphocytes surrounding the islet graft.Results Cotransplantation of islets and 1 × 107 sertoli cells reversed the diabetic state for more than 60days in 100% (6/6) of the chemically diabetic Sprague Dawley rats. Grafts consisting of islets alone or islets plus 1 × 105 sertoli cells survived only for 5 - 6 days. Apoptosis of lymphocytes surrounding the islets was quite clear.Conclusion Cotransplantation of islets with FasL+ sertoli cells induces local immune privilege and allows long-term graft survival without systemic immunosuppression.