title: Growth enhancement by embryonic fibroblasts upon cotransplantation of noncommitted pig embryonic tissues with fully committed organs.
abstract: BACKGROUND
  We recently defined the optimal gestational time windows for the transplantation of several embryonic tissues. We showed that the liver and kidney obtained from E28 pig embryos can grow and differentiate normally after transplantation, whereas 1 week earlier in gestation, these tissues develop into teratoma-like structures or fibrotic mass. In this study, we investigated whether cotransplantation of E28 with E21 tissue could control its tumorogenic potential, or alternatively whether the stem cells derived from the earlier tissue contribute to the growth of the more committed one.
  
  
  METHODS
  Pig embryonic precursors from E21 and E28 gestational age were transplanted alone or together, into nonobese diabetic/severe combined immunodeficiency mice, and their growth and differentiation was evaluated by immunohistology. In situ analysis, based on sex disparity between the E21 and E28 tissues, was used to identify the tissue source. In some experiments, mouse embryonic fibroblasts (MEF) were cotransplanted with E28 liver, and their effect was evaluated.
  
  
  RESULTS
  E28 tissues could not abrogate the propensity of the cells within the undifferentiated tissue to form teratoma-like structures. However, E21 kidney or liver tissue markedly enhanced the growth and function of E28 kidney, liver, and heart grafts. Moreover, similar growth enhancement was observed on coimplantation of E28 liver tissue with MEF or on infusion of MEF culture medium, indicating that this enhancement is likely mediated through soluble factors secreted by the fibroblasts.
  
  
  CONCLUSIONS
  Our results suggest a novel approach for the enhancement of growth and differentiation of transplanted embryonic tissues by the use of soluble factors secreted by embryonic fibroblasts.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Cohen
authors.forename: Dalit
authors.initials: D
authors.lastname: Tchorsh-Yutsis
authors.forename: Anna
authors.initials: A
authors.lastname: Aronovich
authors.forename: Orna
authors.initials: O
authors.lastname: Tal
authors.forename: Smadar
authors.initials: S
authors.lastname: Eventov-Friedman
authors.forename: Helena
authors.initials: H
authors.lastname: Katchman
authors.forename: Yael
authors.initials: Y
authors.lastname: Klionsky
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000637:transplantation*; D005865:Gestational Age; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology; D007668:Kidney / Q000196:embryology; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology; D008099:Liver / Q000196:embryology / Q000254:growth & development; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011247:Pregnancy; D033581:Stem Cell Transplantation / Q000379:methods; D013552:Swine / Q000196:embryology*; D016378:Tissue Transplantation / Q000379:methods*