London, Canada -
Antibody-mediated acute vascular rejection (AVR) is a major problem in organ transplantation. The C3H to BALB/c heterotopic (second heart) cardiac transplant model resembles the human condition of AVR. When recipients are given a course of the conventionally used immune suppressant agent cyclosporin A, grafts survive 15 days. This is approximately 8 days more than if left untreated.
A recent study (Wang et al. Free bone graft attenuates acute rejection and in combination with cyclosporin a leads to indefinite cardiac allograft survival. J Immunol. 2009 May 15;182(10):5970-81) demonstrated that addition of donor or third party bone graft to the cyclosporin immune suppression leads to indefinite allograft survival, associated with lack of AVR.
The investigators found that this immune modulation was associated with generation of T regulatory cells and tolerogenic dendritic cells. Furthermore investigators demonstrated that the immune modulatory component of the free bone graft was radioresistant. While bone marrow mononuclear cells had no effect on survival.
Medistem's Thomas Ichim was listed as a co-author on this publication.
The possibility of using stem cells to immune modulate has previously been explored by this group (Dr. Hao Wang and Medistem) in a publication using fat stem cells to alter the course of multiple sclerosis. It will be interesting to see if these adipose-based approaches will also be translated into the field of transplantation tolerance.