Objectives: Bone marrow (BM) has been recently shown to be an alternative and potentially immune-privileged site for islet transplantation. The aim of the study was to assess the survival of non-encapsulated and encapsulated xenogeneic islets transplanted into the BM of C57BL/6 mice, and to characterize the rejection.
Methods: Rat or human islets were transplanted into the medullary cavity of the femur (n=18) or under the kidney capsule (n=19) of streptozotocin-induced diabetic C57BL/6 mice. Rejection was characterized seven days after rat islets transplantation using non-diabetic mice. Bones were harvested for quantification of CD4, CD8, and F4/80 expression by flow cytometry and immunofluorescence; splenocytes were isolated for in vitro proliferation assays. The survival and fibrotic reaction of encapsulated rat islets were assessed by insulin and Masson staining one month after transplantation in the BM or under the kidney capsule.
Results: Free rat and human islets transplanted into the BM had a median survival of 9 and 7 days respectively. After transplantation under the kidney capsule, rat islets lasted for 14 days (p=0.005) and human islets for 10 days (p=0.004). Seven days after transplantation, increased numbers of CD8 cells were present in femurs of transplanted mice compared to contralateral femur or to naÏve mice femur. CD4, CD8, Macrophages were recruited around the islets in the BM. Splenocytes of transplanted mice specifically proliferate in contact to donor stimulators. Encapsulated rat islets transplanted in the BM had similar insulin positivity and fibrotic reaction when compared to encapsulated islet transplanted under the kidney capsule.
Conclusion: We successfully established an animal model for xenogeneic islets transplantation into the BM. There was no evidence for an immune-privileged environment. The xenorejection in the BM is cellular-dependent with antigen recognition in the spleen. Nevertheless, the BM may represent an adequate site for encapsulated xenogeneic islets transplantation.
To cite this abstract in AMA style:Meier R, Seebach J, Morel P, Mahou R, Bosco D, Berney T, Buhler L, Muller Y. Survival of Free and Encapsulated Islet Xenografts Transplanted in the Mouse Bone Marrow, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/survival-of-free-and-encapsulated-islet-xenografts-transplanted-in-the-mouse-bone-marrow-the/. Accessed May 17, 2021.
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