title: Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation.
abstract: BACKGROUND
  In utero transplantation (IUT) has the potential to treat birth defects early before full development of the immune system. Relatively small grafts, which are not matched for major histocompatibility antigens, can be delivered even before onset of disease symptoms. IUT of hematopoietic stem cells is usually performed via intraperitoneal injection, yet the fate of donor cells in the peritoneal cavity is not fully understood. We review our recent work and present new data demonstrating that the peritoneum can be a site of ectopic hematopoiesis with implications for IUT and immune tolerance induction.
  
  
  METHODS
  Haplogeneic and allogeneic fetal transplants were performed in mice and engraftment tracked by flow cytometry. Immune tolerance was studied by mixed lymphocyte reactions and skin transplantation. Adult syngeneic murine transplants and xenogeneic human into immunodeficient mouse transplants were performed to follow hematopoietic retention in the peritoneum and engraftment of the marrow.
  
  
  RESULTS
  Although most transplanted cells rapidly clear the peritoneum, hematopoietic cells and cells with the phenotype of hematopoietic precursors can remain in the peritoneal cavity for months after transplant. The presence of donor cells in the peritoneum can contribute to donor-specific tolerance, but sufficient peripheral blood chimerism is required to ensure acceptance of donor skin grafts.
  
  
  CONCLUSIONS
  Ectopic hematopoiesis and the survival of stem cells in the peritoneum offer the possibility of better using the peritoneal cavity to delivery stem cells and foster the development of immune tolerance to alloantigens or other foreign antigens.
authors.affiliation: Blood Systems Research Institute, San Francisco, California 94118, USA. mmuench@bloodsystems.org
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.forename: Jeng-Chang
authors.initials: JC
authors.lastname: Chen
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Beyer
authors.forename: Marina E
authors.initials: ME
authors.lastname: Fomin
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D019070:Cell Lineage; D005260:Female; D046128:Fetal Therapies / Q000379:methods*; D030342:Genetic Diseases, Inborn / Q000628:therapy*; D006411:Hematopoiesis, Extramedullary; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D007274:Injections, Intraperitoneal; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010529:Peritoneal Cavity / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D016038:Skin Transplantation / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D018183:Transplantation Chimera / Q000276:immunology*; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic
chemical_list: D007519:Isoantigens
references.citation: J Immunol. 1994 Mar 15;152(6):3098-106
references.pmid: 8144905
references.citation: Chimerism. 2010 Jul-Sep;1(1):36-8
references.pmid: 21327151
references.citation: Am J Transplant. 2008 Nov;8(11):2307-15
references.pmid: 18925902
references.citation: Bone Marrow Transplant. 2005 Mar;35(6):537-47
references.pmid: 15665844
references.citation: Cell Immunol. 2001 Dec 15;214(2):110-22
references.pmid: 12088410
references.citation: Cell Transplant. 2008;17(5):495-506
references.pmid: 18714669
references.citation: Hum Immunol. 2000 Jun;61(6):548-54
references.pmid: 10825582
references.citation: Blood. 1994 Jul 15;84(2):421-32
references.pmid: 7517715
references.citation: Eur J Immunol. 2005 Feb;35(2):383-90
references.pmid: 15682453
references.citation: Blood. 1996 May 15;87(10):4109-19
references.pmid: 8639768
references.citation: Fetal Diagn Ther. 1995 Jul-Aug;10(4):211-78
references.pmid: 7669250
references.citation: Science. 1945 Oct 19;102(2651):400-1
references.pmid: 17755278
references.citation: Int J Dev Biol. 2010;54(2-3):531-43
references.pmid: 19924635
references.citation: Transpl Int. 1998;11(2):82-8
references.pmid: 9561673
references.citation: Fetal Diagn Ther. 2005 Jan-Feb;20(1):35-43
references.pmid: 15608458
references.citation: Fetal Diagn Ther. 2004 Jul-Aug;19(4):305-12
references.pmid: 15192288
references.citation: Cell Transplant. 2010;19(12):1609-22
references.pmid: 20719075
references.citation: Br J Surg. 1996 Aug;83(8):1031-6
references.pmid: 8869299
references.citation: Blood. 1994 Jun 1;83(11):3170-81
references.pmid: 7514903
references.citation: Cell. 2005 Jul 1;121(7):1109-21
references.pmid: 15989959
references.citation: Curr Opin Crit Care. 2001 Apr;7(2):105-16
references.pmid: 11373519
references.citation: Transplant Proc. 2005 May;37(4):1940-1
references.pmid: 15919511
references.citation: Blood. 2004 Dec 1;104(12):3821-8
references.pmid: 15280193
references.citation: Lancet. 1996 Nov 30;348(9040):1484-7
references.pmid: 8942778
references.citation: Stem Cell Stud. 2010 Nov 23;1(1):
references.pmid: 21603093
references.citation: J Immunol. 2005 May 15;174(10):6477-89
references.pmid: 15879151
references.citation: J Exp Med. 1995 Apr 1;181(4):1445-58
references.pmid: 7699329
references.citation: Dev Comp Immunol. 2003 Dec;27(10):899-914
references.pmid: 12880639
references.citation: Science. 1988 Sep 30;241(4874):1815-7
references.pmid: 3051377
references.citation: Transfusion. 2008 Mar;48(3):553-60
references.pmid: 18067493
references.citation: Br J Haematol. 2000 Apr;109(1):173-81
references.pmid: 10848797
references.citation: J Immunol. 2006 May 15;176(10):5741-8
references.pmid: 16670279
references.citation: Blood. 1997 Dec 15;90(12):5002-12
references.pmid: 9389720
references.citation: J Immunol. 1985 Sep;135(3):1752-9
references.pmid: 3926883
references.citation: Br J Haematol. 2004 Aug;126(3):377-84
references.pmid: 15257710
references.citation: J Immunol. 2003 Nov 15;171(10):5554-61
references.pmid: 14607963
references.citation: Science. 2008 Dec 5;322(5907):1562-5
references.pmid: 19056990
references.citation: Bone Marrow Transplant. 2001 Feb;27(4):355-64
references.pmid: 11313664
references.citation: N Engl J Med. 1998 Dec 3;339(23):1657-64
references.pmid: 9834302
references.citation: Blood. 1991 Mar 15;77(6):1218-27
references.pmid: 1705833
references.citation: N Engl J Med. 1996 Dec 12;335(24):1806-10
references.pmid: 8943162
references.citation: Blood. 2005 Jun 15;105(12):4715-21
references.pmid: 15731180