title: Mobilized human hematopoietic stem/progenitor cells promote kidney repair after ischemia/reperfusion injury.
abstract: BACKGROUND
  Understanding the mechanisms of repair and regeneration of the kidney after injury is of great interest because there are currently no therapies that promote repair, and kidneys frequently do not repair adequately. We studied the capacity of human CD34(+) hematopoietic stem/progenitor cells (HSPCs) to promote kidney repair and regeneration using an established ischemia/reperfusion injury model in mice, with particular focus on the microvasculature.
  
  
  RESULTS
  Human HSPCs administered systemically 24 hours after kidney injury were selectively recruited to injured kidneys of immunodeficient mice (Jackson Labs, Bar Harbor, Me) and localized prominently in and around vasculature. This recruitment was associated with enhanced repair of the kidney microvasculature, tubule epithelial cells, enhanced functional recovery, and increased survival. HSPCs recruited to kidney expressed markers consistent with circulating endothelial progenitors and synthesized high levels of proangiogenic cytokines, which promoted proliferation of both endothelial and epithelial cells. Although purified HSPCs acquired endothelial progenitor markers once recruited to the kidney, engraftment of human endothelial cells in the mouse capillary walls was an extremely rare event, indicating that human stem cell mediated renal repair is by paracrine mechanisms rather than replacement of vasculature.
  
  
  CONCLUSIONS
  These studies advance human HSPCs as a promising therapeutic strategy for promoting renal repair after injury.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Amy
authors.initials: A
authors.lastname: Cohen
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hudson
authors.forename: Delara
authors.initials: D
authors.lastname: Motlagh
authors.forename: David L
authors.initials: DL
authors.lastname: Amrani
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries / Q000473:pathology; D002465:Cell Movement; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004847:Epithelial Cells; D005355:Fibrosis / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007121:Immunocompetence; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000098:blood supply / Q000503:physiopathology; D051379:Mice / Q000276:immunology; D008833:Microcirculation; D019899:Paracrine Communication; D020127:Recovery of Function; D012038:Regeneration; D015427:Reperfusion Injury / Q000503:physiopathology*; D016019:Survival Analysis; D014945:Wound Healing
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor
references.citation: J Clin Invest. 1997 Dec 1;100(11 Suppl):S25-9
references.pmid: 9413397
references.citation: N Engl J Med. 2005 Sep 8;353(10):999-1007
references.pmid: 16148285
references.citation: J Am Soc Nephrol. 2007 Nov;18(11):2921-8
references.pmid: 17942965
references.citation: Am J Pathol. 2003 Dec;163(6):2289-301
references.pmid: 14633603
references.citation: Kidney Int. 2007 Jul;72(2):151-6
references.pmid: 17495858
references.citation: Am J Pathol. 2010 Jan;176(1):85-97
references.pmid: 20008127
references.citation: J Thromb Haemost. 2006 Mar;4(3):671-7
references.pmid: 16460450
references.citation: Circ Res. 2005 Aug 19;97(4):314-22
references.pmid: 16020753
references.citation: Am J Physiol Renal Physiol. 2001 Nov;281(5):F887-99
references.pmid: 11592947
references.citation: J Immunol. 2009 Nov 15;183(10):6733-43
references.pmid: 19864592
references.citation: Nat Med. 2004 Aug;10(8):858-64
references.pmid: 15235597
references.citation: Nephrol Dial Transplant. 2008 Jul;23(7):2126-8
references.pmid: 18587158
references.citation: J Clin Invest. 2005 Jul;115(7):1743-55
references.pmid: 16007251
references.citation: Nat Med. 2003 Jun;9(6):702-12
references.pmid: 12778169
references.citation: Mod Pathol. 2008 Jul;21(7):837-46
references.pmid: 18487998
references.citation: J Clin Invest. 2004 Aug;114(3):330-8
references.pmid: 15286799
references.citation: Blood. 2005 Oct 1;106(7):2347-55
references.pmid: 15985545
references.citation: Stem Cells. 2008 Mar;26(3):819-30
references.pmid: 18192236
references.citation: J Am Soc Nephrol. 2007 Apr;18(4):1292-8
references.pmid: 17314324
references.citation: Nat Rev Cancer. 2006 Nov;6(11):835-45
references.pmid: 17036040
references.citation: Stem Cells Dev. 2009 Apr;18(3):475-85
references.pmid: 18564903
references.citation: Bone. 2008 Sep;43(3):434-9
references.pmid: 18547890
references.citation: Stem Cells. 2006 May;24(5):1185-93
references.pmid: 16410390
references.citation: Am J Pathol. 2006 Aug;169(2):372-87
references.pmid: 16877340
references.citation: J Am Soc Nephrol. 1998 Feb;9(2):231-42
references.pmid: 9527399
references.citation: Am J Pathol. 2006 Oct;169(4):1440-57
references.pmid: 17003498
references.citation: Nature. 2005 Dec 15;438(7070):932-6
references.pmid: 16355210
references.citation: Kidney Int. 2006 Jan;69(2):323-30
references.pmid: 16408122
references.citation: Kidney Int. 2008 Aug;74(3):257-8
references.pmid: 18626492
references.citation: Blood Cells. 1994;20(2-3):411-23
references.pmid: 7538347
references.citation: J Am Soc Nephrol. 2007 Sep;18(9):2486-96
references.pmid: 17656474
references.citation: Am J Physiol Cell Physiol. 2004 Sep;287(3):C572-9
references.pmid: 15308462
references.citation: Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):270-1
references.pmid: 15681306
references.citation: J Mol Med (Berl). 2004 Oct;82(10):671-7
references.pmid: 15322703
references.citation: Ann Intern Med. 2002 Jan 1;136(1):54-71
references.pmid: 11777364
references.citation: J Hepatol. 2006 Jul;45(1):13-9
references.pmid: 16635534
references.citation: N Engl J Med. 1996 May 30;334(22):1448-60
references.pmid: 8618585
references.citation: J Clin Invest. 2003 Jul;112(2):160-9
references.pmid: 12865405
references.citation: J Cell Mol Med. 2009 Jan;13(1):87-102
references.pmid: 19067770
references.citation: Trends Mol Med. 2008 Jul;14(7):277-85
references.pmid: 18554984
references.citation: Thromb Haemost. 2005 Feb;93(2):228-35
references.pmid: 15711737
references.citation: J Am Soc Nephrol. 2004 May;15(5):1307-15
references.pmid: 15100371
references.citation: Am J Pathol. 2008 Dec;173(6):1617-27
references.pmid: 19008372
references.citation: Am J Physiol Renal Physiol. 2007 May;292(5):F1626-35
references.pmid: 17213465
references.citation: Hypertension. 1999 Apr;33(4):1013-9
references.pmid: 10205240
references.citation: J Am Soc Nephrol. 2009 Jan;20(1):223-8
references.pmid: 19020007
references.citation: Stem Cells Dev. 2009 Mar;18(2):229-34
references.pmid: 18491948
references.citation: Lancet. 2005 Jan 22-28;365(9456):331-40
references.pmid: 15664230
references.citation: Circulation. 2003 Oct 28;108(17):2070-3
references.pmid: 14568894
references.citation: Am J Physiol Renal Physiol. 2009 Aug;297(2):F461-70
references.pmid: 19458120