Background: It has been demonstrated that embryonic kidneys (metanephroi) xenotransplanted into the omentum of adult recipients continue to develop and display immune protection due to their more naïve immune presentation. To date, this has been achieved using rat, pig and human metanephroi, with unilateral nephrectomy (UNX) of recipient rats a requisite of renal development. The aim of this study was to adapt this approach for use in mice and examine the parameters affecting successful onward development in this species. Methods: Metanephroi at embryonic age (E) 13.5 were transplanted either onto the body wall, abdominal fat pads or omentum of recipient isogenic C57/Bl6 mice using either sutures or polyglycolic acid mesh. Having established greatest success with polyglycolic acid mesh on the body wall, E12.5 and 15.5 days metanephroi from C57/Bl6 mice were then transplanted onto the body wall of control (non-pregnant non-UNX), UNX or 12.5 days post-coitum pregnant isogenic recipients. After 7 days, implanted tissue was harvested and examined using histology and immunohistochemistry for markers of renal maturation. The mean number of S-shaped bodies and glomeruli per section were recorded and statistically analysed for significant differences between all recipient groups and untransplanted metanephroi. The degree of development was scored qualitatively. Results: Transplanted E12.5 metanephroi developed S-shaped bodies and glomeruli in all recipient groups, although there were statistically higher numbers of S-shaped bodies in UNX (n = 2) and pregnant recipients (n = 9) than in control recipients (n = 4). Continued development, as indicated by mature vascularized glomeruli, was only observed in those E15.5 metanephroi transplanted into pregnant recipients (n = 11) with a 15.5-fold increase in S-shaped bodies and 4-fold increase in glomeruli compared with control transplants (n = 12). Conclusions: We have successfully established metanephros transplantation in mice and demonstrated enhancement of onward development of E12.5 metanephroi in response to both pregnancy and UNX. Using E15.5 metanephroi, continued development only occurred in pregnant recipients, implying pregnancy provides an environment conducive to continued organogenesis. This murine assay, when coupled with transgenically-tagged strains of mice, will allow the investigation of the relative contribution of donor and recipient cells to this process.

1.
Steele DJ, Auchincloss H Jr: Xenotransplantation. Annu Rev Med 1995;46:345–360.
2.
Kerr SR, Dalmasso AP, Apasova EV, Chen SS, Kirschfink M, Matas AJ: Mouse-to-rabbit xenotransplantation: a new small animal model of hyperacute rejection mediated by the classical complement pathway. Transplantation 1999;67:360–365.
3.
Magnusson S, Strokan V, Molne J, Nilsson K, Rydberg L, Breimer ME: Blocking of human anti-pig xenoantibodies by soluble GAL α1-3Gal and Gal α1-2Gal disaccharides: studies in a pig kidney in vitro perfusion model. Transpl Int 2000;13:402–412.
4.
Zhan Y, Corbett AJ, Brady JL, Sutherland RM, Lew AM: Delayed rejection of fetal pig pancreas in CD4 cell-deficient mice was correlated with residual helper activity. Xenotransplantation 2000;7:267–274.
5.
Rogers SA, Lowell JA, Hammerman NA, Hammerman MR: Transplantation of developing metanephroi into adult rats. Kidney Int 1998;54:27–37.
6.
Dekel B, Burakova T, Arditti FD, Reich-Zeliger S, Milstein O, Aviel-Ronen S, Rechavi G, Friedman N, Kaminski N, Passwell JH, Reisner Y: Human and porcine early kidney precursors as a new source for transplantation. Nat Med 2003;9:53–60.
7.
Hammerman MR: Distinguished Scientists Lecture Series. New developments in kidney development. Nephron 1999;81:131–135.
8.
Dekel B, Amariglio N, Kaminski N, Schwartz A, Goshen E, Arditti FD, Tsarfaty I, Passwell JH, Reisner Y, Rechavi G: Engraftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal human kidney development. J Am Soc Nephrol 2002;13:977–990.
9.
Dekel B, Reisner Y: Engraftment of human early kidney precursors. Transpl Immunol 2004;12:241–247.
10.
Rogers SA, Hammerman MR: Transplantation of metanephroi after preservation in vitro. Am J Physiol 2001;281:R661–R665.
11.
Rogers SA, Liapis H, Hammerman MR: Transplantation of metanephroi across the major histocompatibility complex in rats. Am J Physiol 2001;280:R132–R136.
12.
Rogers SA, Talcott M, Hammerman MR: Transplantation of pig metanephroi. ASAIO J 2003;49:48–52.
13.
Rogers SA, Hammerman MR: Transplantation of rat metanephroi into mice. Am J Physiol 2001;280:R1865–R1869.
14.
Sasmono RT, Oceandy D, Pollard JW, Tong W, Pavli P, Wainwright BJ, Ostrowski MC, Himes SR, Hume DA: A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood 2003;101:1155–1163.
15.
Okabe M, Ikawa M, Kominami K, Nakanishi T, Nishimune Y: ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett 1997;407:313–319.
16.
Dobson A: An Introduction to Generalised Linear Models. London, Chapman & Hall, 2002.
17.
Chue WL, Campbell GR, Caplice N, Muhammed A, Berry CL, Thomas AC, Bennett MB, Campbell JH: Dog peritoneal and pleural cavities as bioreactors to grow autologous vascular grafts. J Vasc Surg 2004;39:859–867.
18.
Abrahamson DR, St John PL, Pillion DJ, Tucker DC: Glomerular development in intraocular and intrarenal grafts of fetal kidneys. Lab Invest 1991;64:629–639.
19.
Robert B, St John PL, Hyink DP, Abrahamson DR: Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts. Am J Physiol 1996;271:F744–F753.
20.
Shohat J, Davidowitz M, Erman A, Silbergeld A, Boner G: Serum and renal IGF-I levels after uninephrectomy in the rat. Scand J Clin Lab Invest 1997;57:167–173.
21.
Ishibashi K, Sasaki S, Sakamoto H, Hoshino Y, Nakamura T, Marumo F: Expressions of receptor gene for hepatocyte growth factor in kidney after unilateral nephrectomy and renal injury. Biochem Biophys Res Commun 1992;187:1454–1459.
22.
Nishida M, Kawakatsu H, Ishiwari K, Tamai M, Sawada T, Nishimura M, Yoshimura M: Serum hepatocyte growth factor levels in patients with renal diseases. Am J Nephrol 1999;19:509–512.
23.
Takayama H, LaRochelle WJ, Sabnis SG, Otsuka T, Merlino G: Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in transgenic mice overexpressing hepatocyte growth factor/scatter factor. Lab Invest 1997;77:131–138.
24.
Kubota T, Kamada S, Taguchi M, Aso T: Determination of insulin-like growth factor-2 in feto-maternal circulation during human pregnancy. Acta Endocrinol (Copenh) 1992;127:359–365.
25.
Chen C, Spencer TE, Bazer FW: Expression of hepatocyte growth factor and its receptor c-met in the ovine uterus. Biol Reprod 2000;62:1844–1850.
26.
Depret-Mosser S, Jomin M, Monnier JC, Vinatier D, Bouthors-Ducloy AS, Christiaens JL, Krivosic-Horber R: Cerebral tumors and pregnancy. Apropos of 8 cases (in French). J Gynecol Obstet Biol Reprod (Paris) 1993;22:71–80.
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