Date: Monday, June 3, 2019
Session Name: Concurrent Session: Basic & Clinical Science - VCA
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: Room 209
*Purpose: Adipose-derived stem cells (ASC) have increased levels of anti-inflammatory and immunoregulatory factors. Murine studies have shown stable macrochimerism and long-term full thickness skin graft survival after a co-infusion of ASC and bone marrow cells (BMC). We hypothesized that co-infusion of ASC and BMC with a depletional conditioning regimen would promote chimerism and prolong graft survival in an established non-human primate (NHP) facial transplantation model.
*Methods: Three cynomolgus macaques underwent heterotopic facial subunit transplantation from MHC-mismatched donors. Anti-CD4 and Anti-CD8 monoclonal antibodies were administered (50 mg/kg) on postoperative (POD) days 0, 2, 5, 7, and 14 in addition to a non-myeloablative dose of busulfan (5 mg/kg). On POD 7 (20 x 106 cells/kg) adipose-derived stem cells (ASC) and donor vertebral bone marrow (dBMC) were infused. Tacrolimus and mycophenolate mofetil were then administered for maintenance immunosuppression. Clinical evidence of graft rejection was assessed via gross appearance and histopathologic analysis according to Banff classification. Peripheral chimerism was determined via flow cytometry.
*Results: After administration of monoclonal antibodies, CD3+ cells decreased to a mean of 28.4% of baseline, CD4+ cells decreased to a mean of 2.9% of baseline, and CD8+ cells decreased to a mean of 37.0% of baseline. Animal 1 and 2 achieved a mean rejection-free survival of 63.5 days, pathology at the time of necropsy demonstrated Banff 4 rejection. Animal 3 is ongoing without gross or histopathologic evidence of rejection. The maximum level of peripheral chimerism achieved was 6.01%, 13.48%, and 26.1% in Animals 1, 2, and 3 respectively.
*Conclusions: With the ease of acquiring adipose-derived stem cells in the clinical setting and chimerism noted in pre-clinical models, utilizing ASC is a promising method for promoting tolerance and graft survival in highly antigenic transplanted allografts. Developing well-tolerated regimens that lead to improved engraftment is imperative in eliminating complications associated with high levels of long-term immunosuppression.
To cite this abstract in AMA style:Shockcor N, Buckingham B, Hassanein W, Parsell D, Dhru U, Akinsiku B, Elster E, Davis T, Gimble J, Nam A, Bartlett S, Barth R. Adipose Stem Cells Promote Composite Tissue Engraftment [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/adipose-stem-cells-promote-composite-tissue-engraftment/. Accessed July 1, 2020.
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