Introduction: We hypothesized that hematopoietic stem cell (HSC) niches in bone marrow of vascularized osteomyocutaneous allografts (VOMA) will facilitate mixed chimerism (MC) and tolerance to donor matched renal allografts. Our goal was to investigate this novel non-myeloblative tolerance strategy in a non-human primate model.

Methods: Full MHC mismatched, ABO matched, 4-5 year-old (3-4.5 kg) cynomolgus male-female (donor-recipient) NHP pairs (n=4) were used for concomitant donor-matched renal-VOMA transplantation (distal 1/3 of femur). Induction consisted of ATG (Day -4 and -1) and total body irradiation (TBI) (200 cGy, Day -1). Maintenance therapy consisted of tacrolimus (TAC, i.m., b.i.d). MC was monitored by RT-PCR using NHP Y-chromosome (SRY) specific primers.

Results: All recipients developed acute rejection (AR) by 7-10 days in the skin component of the VOMA. Tac levels during AR were 3-6ng/ml. Recipients were received bolus steroid (Solumedrol, 40 mg, IV, 5 days) to rescue AR and converted from TAC to Cyclosporin A (CSA) (b.i.d, target trough range: 400-600ng/mL). Skin component of VOMA in 2 recipients progressed to Banff 3-4 AR (epidermolysis, necrosis) with coincident AR of renal grafts with CSA trough levels ranged between 50-100ng/mL. Two other recipients completely reversed AR of VOMA with CSA levels ranged between 400-600 ng/mL. After 2 months post Tx, CSA levels then tapered to 50-100ng/mL with complete withdrawal on 120 days post Tx. One recipient had increasing Cr levels after 150 days post Tx. Exploratory laparotomy at 180 days confirmed obstructive uropathy. Serum Cr levels were normal in other recipients up to 550 days post Tx. The skin of the VOMA was normal and vascular patency was maintained in all grafts until end point by ultrasound and CT imagingin in both recipients. Donor MC was detectable on RT-PCR up to 60 days post Tx. This is an ongoing study with further Tx underway.

Conclusion: We established a novel NHP model that combines renal and VOMA transplantation. The skin component of the VOMA can serve as a surrogate for renal allograft monitoring. Our preliminary results support the role of donor-matched VOMA in sustaining MC and facilitate renal-VOMA tolerance.

CITATION INFORMATION: Zhong F, Zhao G, Wang Y, Jiang J, Wang Y, Ye S, Tao S, Cai L, Wang X, Ye Q, Chen G, Zheng X. Induction of Tolerance to Renal Allografts in Non Human Primates by Concomitant Donor-Matched Vascularized Osteomyocutaneous Allotransplantation. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress