title: The lymph node as a new site for kidney organogenesis.
abstract: The shortage of organs for kidney transplantation has created the need to develop new strategies to restore renal structure and function. Given our recent finding that the lymph node (LN) can serve as an in vivo factory to generate or sustain complex structures like liver, pancreas, and thymus, we investigated whether it could also support kidney organogenesis from mouse renal embryonic tissue (metanephroi). Here we provide the first evidence that metanephroi acquired a mature phenotype upon injection into LN, and host cells likely contributed to this process. Urine-like fluid-containing cysts were observed in several grafts 12 weeks post-transplantation, indicating metanephroi transplants' ability to excrete products filtered from the blood. Importantly, the kidney graft adapted to a loss of host renal mass, speeding its development. Thus, the LN might provide a unique tool for studying the mechanisms of renal maturation, cell proliferation, and fluid secretion during cyst development. Moreover, we provide evidence that inside the LN, short-term cultured embryonic kidney cells stimulated with the Wnt agonist R-Spondin 2 gave rise to a monomorphic neuron-like cell population expressing the neuronal 200-kDa neurofilament heavy marker. This finding indicates that the LN might be used to validate the differentiation potential of candidate stem cells in regenerative nephrology.
authors: Department of Pathology, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Ri.MED Foundation, Palermo, Italy.
authors: Maria Giovanna
authors: MG
authors: Francipane
authors: Department of Pathology, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Ri.MED Foundation, Palermo, Italy Lagasse@pitt.edu.
authors: Eric
authors: E
authors: Lagasse
mesh_terms: D064591:Allografts; D000818:Animals; D000943:Antigens, Differentiation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D038081:Organogenesis; D033581:Stem Cell Transplantation; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation
keywords: Bioreactor; Kidney; Lymph node; Organogenesis; Stem cells
references: Development. 1995 Mar;121(3):867-75
references: 7720589
references: J Am Soc Nephrol. 2006 Sep;17(9):2443-56
references: 16885410
references: Nat Biotechnol. 2012 Oct;30(10):976-83
references: 23000933
references: Dev Growth Differ. 1993 Apr;35(2):123-128
references: 37281298
references: Transplantation. 2009 Jul 27;88(2):151-9
references: 19623009
references: Oncotarget. 2013 Nov;4(11):1948-62
references: 24185040
references: Development. 1999 Dec;126(24):5847-56
references: 10572058
references: Eur J Surg Suppl. 1997;(577):5-9
references: 9076446
references: Kidney Int. 2005 Nov;68(5):1956-61
references: 16221175
references: Kidney Int. 1998 Jul;54(1):27-37
references: 9648060
references: Genes Dev. 2014 Feb 15;28(4):305-16
references: 24532711
references: Biochemistry. 2013 Oct 15;52(41):7295-304
references: 24050775
references: J Clin Invest. 2004 Sep;114(6):795-804
references: 15372103
references: Nephrol Dial Transplant. 2002;17 Suppl 9:37-8
references: 12386283
references: Am J Physiol. 1996 Sep;271(3 Pt 2):F744-53
references: 8853438
references: Organogenesis. 2011 Apr-Jun;7(2):123-34
references: 21519195
references: Am J Physiol. 1996 May;270(5 Pt 2):F886-99
references: 8928852
references: Clin Transl Med. 2013 May 21;2(1):11
references: 23688352
references: Nature. 2009 May 14;459(7244):262-5
references: 19329995
references: PLoS One. 2012;7(9):e46453
references: 23029522
references: Br J Surg. 2008 Dec;95(12):1449-61
references: 18991254
references: Transplantation. 2013 Dec 27;96(12):1026-33
references: 24056625
references: Eur J Pediatr. 1995;154(9 Suppl 4):S65-8
references: 8529714
references: J Hepatol. 2010 Feb;52(2):211-9
references: 20022655
references: Cell Stem Cell. 2014 Jan 2;14(1):53-67
references: 24332837
references: Gastroenterology. 2011 Feb;140(2):656-666.e2
references: 21070777
references: Lab Invest. 1991 May;64(5):629-39
references: 2030577
references: Am J Physiol Cell Physiol. 2001 Oct;281(4):C1318-25
references: 11546670
references: Sci Rep. 2014 Jan 27;4:3872
references: 24464028
references: Dev Biol. 2007 Nov 1;311(1):124-35
references: 17904116
references: Nephrol Dial Transplant. 2008 Mar;23(3):871-9
references: 17933838
references: Transplantation. 2007 May 15;83(9):1249-58
references: 17496543
references: Dev Growth Differ. 2002 Apr;44(2):161-7
references: 11940102
references: Nat Cell Biol. 2014 Jan;16(1):118-26
references: 24335651
references: PLoS One. 2014 Jan 15;9(1):e84881
references: 24454758
references: Curr Opin Organ Transplant. 2014 Apr;19(2):169-74
references: 24480968
references: Nat Cell Biol. 2013 Dec;15(12):1507-15
references: 24240476
references: J Korean Med Sci. 2010 Feb;25(2):203-10
references: 20119571
references: Am J Physiol Renal Physiol. 2007 Jan;292(1):F269-77
references: 16926446
references: Dev Biol. 2003 Jun 15;258(2):406-18
references: 12798297
references: Exp Physiol. 2007 Jan;92(1):263-71
references: 17085675
references: Nephrol Dial Transplant. 2012 Sep;27(9):3449-55
references: 22513705
references: J Am Soc Nephrol. 2005 Dec;16(12):3527-34
references: 16267156
references: Kidney Int. 2012 Jul;82(2):138-46
references: 22437414
references: Am J Kidney Dis. 2012 Jan;59(1 Suppl 1):A7, e1-420
references: 22177944
references: J Pathol. 2013 Jan;229(2):221-31
references: 23097132
references: J Am Soc Nephrol. 2004 May;15(5):1126-32
references: 15100352
references: Nat Genet. 2006 Nov;38(11):1304-9
references: 17041600
references: J Am Soc Nephrol. 2006 Nov;17(11):3028-40
references: 16988061
references: Nat Rev Immunol. 2001 Nov;1(2):154-60
references: 11905823
references: Diabetes. 2013 May;62(5):1357-64
references: 23613549
references: Kidney Int. 1996 May;49(5):1478-87
references: 8731117