Islet Survival and Function Following Intramuscular Autotransplantation in the Minipig

The liver may not be an optimal site for islet transplantation due to obstacles by an instant blood‐mediated inflammatory response (IBMIR), and low revascularization of transplanted islets. Therefore, intramuscular islet transplantation (IMIT) offers an attractive alternative, based on its simplicit...

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Bibliographic Details
Published in:	American journal of transplantation 2013-04, Vol.13 (4), p.891-898
Main Authors:	Sterkers, A., Hubert, T., Gmyr, V., Torres, F., Baud, G., Delalleau, N., Vantyghem, M. C., Kerr‐Conte, J., Caiazzo, R., Pattou, F.
Format:	Article
Language:	eng
Subjects:	Animals Biological and medical sciences Cell Survival Fibrosis Glucagon - metabolism Glucose - metabolism Graft Survival Hypoxia Injections, Intramuscular Insulin - metabolism Islets of Langerhans - cytology Islets of Langerhans Transplantation - methods Medical sciences Muscles - blood supply Muscles - cytology Neovascularization, Physiologic Pancreas - surgery Porcine islets preclinical studies revascularization suppress engraftment Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Swine Swine, Miniature Transplantation, Autologous Transplantation, Heterotopic Transplants & implants
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Summary:	The liver may not be an optimal site for islet transplantation due to obstacles by an instant blood‐mediated inflammatory response (IBMIR), and low revascularization of transplanted islets. Therefore, intramuscular islet transplantation (IMIT) offers an attractive alternative, based on its simplicity, enabling easier access for noninvasive graft imaging and cell explantation. In this study, we explored the outcome of autologous IMIT in the minipig (n = 30). Using the intramuscular injection technique, we demonstrated by direct histological evidence the rapid revascularization of islets autotransplanted into the gracilius muscle. Islet survival assessment was performed using immunohistochemistry staining for insulin and glucagon up to a period of 6 months. Furthermore, we showed the crucial role of minimizing mechanical trauma to the myofibers and limiting exocrine contamination. Intramuscular islet graft function after transplantation was confirmed by documenting the acute insulin response to intravenous glucose in 5/11 pancreatectomized animals. Graft function after IMIT remained however significantly lower than the function measured in 12 out of 18 minipigs who received a similar islet volume in the liver through intraportal infusion. Collectively, these results demonstrated in a clinically relevant preclinical model, suggest IMIT as a promising alternative to intraportal infusion for the transplantation of β cells in certain medical situations. In this study, the authors demonstrate the interest of muscle as a promising alternative site to intraportal infusion for the transplantation of β‐cell in a preclinical minipig model.
ISSN:	1600-6135 1600-6143