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Growing a Surrogate Organ in Lymph Node

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Abstract

Currently, the shortage of organs available for transplant into terminally ill patients represents a major worldwide medical, social, and economic challenge. For many years, the transplant of (stem) cells to regenerate failing organs has been proposed as an alternative to whole-organ transplantation. However, orthotopic cell-based therapy directed at a diseased organ may not be feasible for many patients. The efficacy of cell-based therapy becomes questionable in disease states which compromise the environment needed for cellular engraftment and function. This is true in many end stage organ failure scenarios such as cirrhotic or fibrotic liver. In another such example, DiGeorge syndrome patients suffer from an absence of thymic development causing severe immunodeficiency. In this instance, ectopic transplantation of allografted tissue is necessary to replace thymic function. Consequently, a critical component of cell therapy for these patients is the establishment of an optimal in vivo ectopic cell or tissue transplant site to achieve restoration of organ function. We have pioneered use of the lymph node as a site for ectopic tissue and organ development. In this chapter, we will discuss two applications, the transplantation of hepatocytes and thymic tissues in lymph node, to develop functional ectopic organs.

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Abbreviations

OLT:

Orthotopic liver transplantation

Fah:

Fumarylacetoacetate hydrolase

NTBC:

2-(2-nitro-4-trifluoro-methylbenzyol)-1,3-cyclohexanedione

IP:

intraperitoneally

SP:

splenic injection

BrdU:

5-Bromo-2′-deoxyuridine

CK8:

cytokeratin 8

CK5:

cytokeratin 5

ES/iPSC:

Embryonic Stem Cells/Induced Pluripotent Stem Cells

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Acknowledgments

This work was supported by the NIH Grant R01-DK085711. We thank Lynda Guzik for proofreading and editing.

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Correspondence to Eric Lagasse .

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Lagasse, E. (2016). Growing a Surrogate Organ in Lymph Node. In: Watanabe, T., Takahama, Y. (eds) Synthetic Immunology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56027-2_8

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