Pancreatic islet cells isolation and transplantation into the bone marrow
Bone marrow is currently being considered as an alternative site for pancreatic islet transplantation. The goal of the present review is to report preclinical and clinical studies taking advantage of this new implantation site. Preclinical studies in mice demonstrated that syngeneic islets could survive in bone marrow indefinitely with a higher success in providing euglycemia compared to islets transplanted into the traditionally used implantation site, namely, the liver. In concordant and discordant xenogeneic models, the immune response was more stringent when islets were transplanted to the bone marrow as compared to the traditional implantation site in rodents, the kidney capsule. As demonstrated by histology, cellular and humoral rejection was prevented by islets protected by micro-encapsulation in calcium-alginate beads, and a similar degree of fibrotic reaction was induced at both site, although functional studies in diabetic animals are still needed. In clinical settings, a pilot study of four patients who received islet auto-transplantation into the bone marrow after a total pancreatectomy had been showed to be safe and feasible. Three out of four patients had a functioning graft, as measured by serum C-peptide, at an average follow-up of 545 ± 369 days. In conclusion, islet transplantation into the bone marrow may be a viable alternative to the liver as an implantation site, particularly with the perspective of transplanting encapsulated xenogeneic islets. Meanwhile, the efficacy of immunosuppressive drugs would still require to be evaluated in allogeneic and xenogeneic preclinical models of islet transplantation into the bone marrow.