Reinnervation of Syngeneic Mouse Pancreatic Islets Transplanted Into Renal Subcapsular Space

Abstract

A syngeneic transplantation of 150 islets into the subcapsular renal space was performed on normoglycemic or alloxan-induced diabetic male C57BL/6 mice. Six, 8, 14, or 20-21 wk after transplantation, the graft-bearing kidney was removed and processed for microscopical examinations with indirect immunofluorescence for neuropeptides and tyrosine hydroxylase, and with acetylcholinesterase staining to visualize nerve fibers within the graft. Six weeks after implantation, only a few scattered nerve fibers were observed within the grafts. A progressive increase in the number of nerves was observed until 14 wk after transplantation, after which, a stable level was reached. Alloxan-induced diabetic mice showed quantitatively and qualitatively similar reinnervation to normoglycemic mice 20 wk after transplantation. The findings demonstrate the presence of sympathetic nerve fibers (containing tyrosine hydroxylase and neuropeptide Y), mainly accompanying ingrowing blood vessels; parasympathetic nerve fibers (containing acetylcholinesterase and vasoactive intestinal peptide), possibly reaching the graft from the adjacent renal capsule; and afferent nerve fibers (containing substance P and calcitonin gene-related peptide), which were less numerous. The data suggest that transplanted islets become reinnervated by ingrowth of nerve fibers from the implantation organ and that several types of nerves are present.

Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function

“…Islets are reinnervated after transplantation, both in the eye (present results and ref. 42) and elsewhere (43)(44)(45)(46). Independently of the transplantation site, the innervation pattern of the islet grafts seems to differ only slightly from that in the native pancreas (43,45).…”

Initial increase and subsequent loss of vasoactive intestinal polypeptide immunoreactivity in acetylcholinesterase-positive neurons of mouse islets transplanted to the kidney

“…In islets transplanted to the kidney, a progressive reinnervation of the grafts with cholinergic and VIP-ergic nerves has been interpreted as originating from the renal capsule (Korsgren et al 1992). Unlike whole-pancreatic fragments transplanted to the spleen (Madureira et al 1985), islet grafts allegedly contained no nerve cell bodies (Korsgren et al 1992(Korsgren et al , 1993.…”

“…Unlike whole-pancreatic fragments transplanted to the spleen (Madureira et al 1985), islet grafts allegedly contained no nerve cell bodies (Korsgren et al 1992(Korsgren et al , 1993. To explain this apparent discrepancy, Korsgren et al (1992) envisaged the disappearence of neuroinsular complexes during preparatory culture of the islets to be transplanted.…”

“…Unlike whole-pancreatic fragments transplanted to the spleen (Madureira et al 1985), islet grafts allegedly contained no nerve cell bodies (Korsgren et al 1992(Korsgren et al , 1993. To explain this apparent discrepancy, Korsgren et al (1992) envisaged the disappearence of neuroinsular complexes during preparatory culture of the islets to be transplanted. Several authors have interpreted the reinnervation of transplanted islets as originating from the implantation organ (Korsgren et al 1992(Korsgren et al , 1993Noda et al 1993;Gardemann et al 1994;Portis et al 1994).…”

“…To explain this apparent discrepancy, Korsgren et al (1992) envisaged the disappearence of neuroinsular complexes during preparatory culture of the islets to be transplanted. Several authors have interpreted the reinnervation of transplanted islets as originating from the implantation organ (Korsgren et al 1992(Korsgren et al , 1993Noda et al 1993;Gardemann et al 1994;Portis et al 1994). To our knowledge, no report exists on the intrinsic regeneration of nerve fibers from existing nerve cell bodies in the transplanted islets.…”