Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Coinfusion
Technical Report,15 Aug 2016,14 Aug 2018
Columbia University Medical Center New York United States
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While composite tissue reconstruction in the form of composite tissue allografts represents a therapeutic option in the treatment of congenital abnormalities, oncologic surgery and traumatic injuries, immunological rejection of the allograft remains the major barrier for this therapy and its avoidance requires life-long potent immunosuppression, which itself has life-threatening adverse effects. Induction of tolerance to allografts is the ideal solution. Induction of durable mixed allogeneic hematopoietic chimerism via hematopoietic cell transplant HCT has been shown to be a powerful approach to inducing tolerance to allografts in rodents. However, it is much more difficult to achieve durable mixed chimerism in large animals Non-human primates and humans. Human Amnion-derived multipotent progenitor AMP cells possess a unique immune phenotype and low immunogenicity and demonstrate immunosuppressive activities in vitro and in vivo in mouse models. We have investigated whether co-transplantation of human AMP cells can promote the induction of durable mixed allogeneic chimerism in a highly clinically relevant non-human primate HCT model. Our results show that intravenous injection of high dose 100millionkg of AMP cells did not prolong mixed chimerism or facilitate induction of tolerance to an allograft, in association with lack of persistence of AMP cells in vivo. We detected anti-AMP cell natural antibodies in recipient monkeys, which may explain the lack of persistence of AMP cells in vivo. We then screened candidate animals to select those with low anti-AMP cell natural antibodies as transplant recipients and co-transplanted AMP cells via intrabone injection, hoping that direct delivery of AMP cells to their effector sites could facilitate exertion of their immunosuppressive effects.
- Medicine and Medical Research