The mouse lymph node as an ectopic transplantation site for multiple tissues

Abstract

Cell-based therapy has been viewed as a promising alternative to organ transplantation, but cell transplantation aimed at organ repair is not always possible. Here we show that the mouse lymph node can support the engraftment and growth of healthy cells from multiple tissues. Direct injection of hepatocytes into a single mouse lymph node generated enough ectopic liver mass to rescue the survival of mice with lethal metabolic disease. Furthermore, thymuses transplanted into single lymph nodes of athymic nude mice generated functional immune systems that were capable of rejecting allogeneic and xenogeneic grafts. Additionally, pancreatic islets injected into the lymph nodes of diabetic mice restored normal glucose control. Collectively, these results suggest the practical approach of targeting lymph nodes to restore, maintain or improve tissue and organ functions.

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Figure 1: Direct injection of hepatocytes into a single lymph node of a C57BL/6 wild-type mouse.
Figure 2: Direct injection of hepatocytes into a single lymph node of a Fah−/− mouse.
Figure 3: Functional ectopic thymus in the jejunal lymph node.
Figure 4: Ectopic pancreas generation in the jejunal lymph node after islet transplantation.
Figure 5: Neovascularization of ectopic tissue.

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Acknowledgements

We would like to thank S. Thorne and R. Sikorski for the in vivo imaging and the luciferase C57BL/6 transgenic mice. 129sv and 129sv Fah−/− mice were a kind gift from M. Grompe (Oregon Health and Sciences University). CTLA4-Ig and MR1 antibodies were a kind gift from F. Lakkis (University of Pittsburgh). This project used University of Pittsburgh Cancer Institute shared resources that are supported in part by award P30CA047904. This work was supported by the US National Institutes of Health grant R01 DK085711 (J.K., L.B., A.D. and E.L.).

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J.K., L.B. and A.D. performed and analyzed experiments for liver, thymus and pancreatic islets, respectively. T.H. conducted experiments. J.K., L.B., A.D. and E.L. designed experiments and wrote the manuscript. E.L. performed overall project planning and coordination. All authors edited and approved the final manuscript.

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Correspondence to Eric Lagasse.

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The authors declare no competing financial interests.

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Komori, J., Boone, L., DeWard, A. et al. The mouse lymph node as an ectopic transplantation site for multiple tissues. Nat Biotechnol 30, 976–983 (2012). https://doi.org/10.1038/nbt.2379

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