Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Coinfusion
Abstract
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 (100million/kg) 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2018
- Accession Number
- AD1095138
Entities
People
- Megan Sykes
Organizations
- Columbia University Irving Medical Center