Research Article: Therapeutic Effects of HLA-G Overexpressing hAMSCs on aGVHD After Allo-HSCT: Involving in the Gut Microbiota at the Intestinal Barrier
Abstract:
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a promising cellular therapy to cure various hematological malignancies, non-hematological malignancies and some genetic and metabolic diseases. However, acute graft-versus-host disease (aGVHD), in which donor-derived T cells recognize recipient tissues as heterologous, resulting in high morbidity and mortality, remains the main cause of short-term death after allo-HSCT and the major obstacle to allo-HSCT. Systemic corticosteroids are still the standard first-line therapy for aGVHD, whereas ~% of patients are refractory to steroid therapy. There was no uniformly adopted or approved second-line therapy for patients with steroid-refractory aGVHD (SR-aGVHD), whose -year overall survival is only %., It is thus the impetus to develop more effective strategies for this devastating disease while maintaining graft-versus-leukemia (GVL) effects to avoid a potential increase in recurrence-related mortality. The gastrointestinal tract, harboring a dense and diverse microbial community, is the primary severely affected target organ by aGVHD. Under physiological conditions, the crosstalk between the intestinal barrier, immunity, gut microbiota and its metabolites is in a steady state, maintaining intestinal homeostasis and protecting against pathogens. During allo-HSCT, antibiotics and conditioning regimen including radiotherapy and chemotherapy result in the brokenness of intestinal homeostasis including intestinal barrier damage and gut microbiota dysbiosis. Antigen presenting cells recognize gut microbiota components, which induce T cell immune imbalance and inflammatory cascade to exacerbate tissue damage and promote aGVHD development. Thus, it is the imputes to maintain the homeostasis in the intestines to reduce aGVHD.
Introduction:
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a promising cellular therapy to cure various hematological malignancies, non-hematological malignancies and some genetic and metabolic diseases. However, acute graft-versus-host disease (aGVHD), in which donor-derived T cells recognize recipient tissues as heterologous, resulting in high morbidity and mortality, remains the main cause of short-term death after allo-HSCT and the major obstacle to allo-HSCT. Systemic corticosteroids are still the…
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