Hematopoietic stem cells as inducers of tolerance to solid organ transplants

2004 ◽  
Vol 9 (3) ◽  
pp. 279-283
Author(s):  
Michel Goldman ◽  
Vincent Donckier ◽  
Michel Toungouz
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2204-2204
Author(s):  
Mary-Elizabeth A. Muchmore ◽  
Matthew J. Burge ◽  
Judith A. Shizuru

Abstract Transplantation of purified allogeneic hematopoietic stem cells (HSC) has the potential to be a curative treatment for autoimmune diseases. Before it becomes a viable therapy, however, the treatment-related mortality and difficulty of achieving engraftment must be addressed. Our research has focused on developing non-myeloablative regimens that lead to donor-derived engraftment of purified HSC in a murine model. Total lymphoid irradiation (TLI) consists of low-dose fractionated irradiation targeted to the thymus, abdomen, and peripheral nodes, while the skull, lungs, and long bones remain shielded. The non-myeloablative conditioning regimen of TLI and anti-thymocyte globulin (ATG) was followed by HSC transplantation. HSCs were isolated by the composite phenotype of Thy1.1+, c-kit+, Sca-1+, and lineage- (KTLS) or, in strains lacking the Thy1.1 marker, c-kit+, Sca-1+, and lineage- (KSL). We tested HSC transplantations across three major histocompatiblity complex (MHC)-matched strain combinations known through previous studies in our group to have significantly different barriers to engraftment. In all three strain combinations we observed stable mixed chimerism (approximately 50% donor-derived cells) when high doses of HSC (10,000/mouse) were administered. Chimerism was measured at thirty-day intervals, and initially sharply increased and then stabilized around day ninety post-transplantation. In prior studies from our laboratory in a spontaneously arising autoimmune diabetes model, we demonstrated that mixed allogeneic chimerism alone following low dose total body irradiation (TBI) and HSC transplantation was sufficient to block the autoimmune pathogenesis. In order to establish a second clinically relevant conditioning regimen, we attempted here to lower the dose of TBI by using cyclophosphamide and ATG in addition to low dose TBI. However, less robust engraftment was observed as compared to the TLI/ATG approach. To study how TLI/ATG allows engraftment, we have examined the marrow of TLI/ATG conditioned, untransplanted animals. Though TUNEL and Caspase-3 assays did not show a significant increase in apoptosis compared to controls, a 71% decrease in the quantitative number of HSCs isolated from these animals was observed. This depletion of HSCs in the marrow could provide a niche for donor HSCs to inhabit. Further histologic studies on lymphoid organs exposed to radiation through TLI, including the thymus and spleen, are ongoing and may further elucidate the mechanisms by which TLI reconditions the host immune system. The durable mixed chimerism observed following TLI/ATG conditioning and HCT will be applied to mice affected with the rodent form of multiple sclerosis (experimental autoimmune encephalomyelitis) and to tolerance induction of solid-organ grafts. SUMMARY: The combination of TLI/ATG non-myeloablative conditioning and transplantation of allogeneic HSC leads to a durable mixed chimeric state between donor and host and will next be applied to the induction of tolerance to autoantigens and alloantigens.


2020 ◽  
pp. 106-106
Author(s):  
Olivera Jovicic ◽  
Jelena Mandic ◽  
Zoran Mandinic ◽  
Aleksandra Colovic

Introduction/Objective. The aim of this paper is to point out the prevalence and severity of oral diseases in patients in the period before and after the transplantation of solid organs and hematopoietic stem cells. Methods. MEDLINE literature search was done via PubMed. Results. The development and improvement of transplantation medicine in specialized centers lead to an increasing number of patients, both adults and children, with transplanted solid organs and hematopoietic stem cells. Despite the success of therapy, numerous changes and complications can be observed on other organs in patients undergoing transplantation of solid organs and hematopoietic stem cells in the pre and post-transplant phase. Systemic diseases and conditions related to organ and cell transplantation, which are accompanied by numerous oral manifestations. The most common oral changes are gingival enlargement, desquamation of the oral epithelium, very painful ulcerations, polypoid and granulomatous changes in the oral mucosa, hard dental tissues with frequent complications, developmental anomalies of teeth in younger children, and in the later stage also the occurrence of oral cancer. After transplantation of solid organs and hematopoietic changes in the oral cavity and other organs occur depending on the patient?s post- transplantation period as well as on the applied immunosuppressive therapy. Conclusion. Oral changes development pre and post transplantation of solid organ and hematopoietic stem cells points to the importance of timely and good cooperation between the dentist and the doctor who treats the underlying disease.


2016 ◽  
Vol 30 (4) ◽  
pp. 227-234 ◽  
Author(s):  
Reza Elahimehr ◽  
Andrew T. Scheinok ◽  
Dianne B. McKay

2006 ◽  
Author(s):  
Hideyo Hirai ◽  
Pu Zhang ◽  
Tajhal Dayaram ◽  
Christopher Hetherington ◽  
Shin-ichi Mizuno ◽  
...  

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