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Problems associated with the use of dispersed pancreatic tissue for xenotransplantation: A possible solution
Author(s) -
Wahoff David C.,
Nelson Lindsey A.,
Sutherland David E.R.,
Gores Paul F.
Publication year - 1995
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.1995.tb00075.x
Subject(s) - xenotransplantation , islet , peritoneal cavity , transplantation , medicine , pancreas , diabetes mellitus , intraperitoneal injection , pancreatectomy , urology , group a , andrology , surgery , endocrinology
In light of the disappointing clinical results with purified islets, we propose that a simple preparation of impure islets may provide a better graft for both future allogeneic and xenogeneic transplantation trials. We hypothesize that the simplest, least traumatic procedure to disperse the pancreas, which minimizes the disruption of normal cellular associations, will yield an islet graft of maximum viability. The peritoneal cavity is an attractive site for the transplantation of such preparations since it can accommodate nearly unlimited graft volumes, and is easily accessible. In the present study, we tested the ability of impure islet autografts transplanted in the peritoneal cavity to reverse diabetes in a preclinical model. Dogs (N=29) underwent total pancreatectomy and were divided into three groups: group I (N=7) received intraportal pure islets; group II (N=13) received intraperitoneal pure islets; group III (N=9) received intraperitoneal impure islets. There were no significant differences in islet mass transplanted in the groups: group I 11,686 ± 2,514 IE/kg, group II 10,274 ± 1,125 IE/kg, and group III 11,735 ± 1,497. At 15 months, all purified grafts in group I failed, and all but one purified graft in group II failed, while five impure grafts in group III continued to function ( P < 0.05, versus group I and II, X 2 ). Glucose disposal in dogs with functioning grafts did not differ between groups. In conclusion, free impure islets are able to engraft within the peritoneal cavity and reverse diabetes in a large animal. Impure islets grafts were superior to purified grafts in initial engraftment and long‐term functional survival. Thus, the peritoneal cavity represents a site that can support the engraftment and long‐term function of both impure islet allografts and possibly xenografts if sufficient immune suppression or tolerance is achieved.