TY - JOUR
T1 - Growth enhancement by embryonic fibroblasts upon cotransplantation of noncommitted pig embryonic tissues with fully committed organs
AU - Cohen, Sivan
AU - Tchorsh-Yutsis, Dalit
AU - Aronovich, Anna
AU - Tal, Orna
AU - Eventov-Friedman, Smadar
AU - Katchman, Helena
AU - Klionsky, Yael
AU - Shezen, Elias
AU - Reisner, Yair
PY - 2010/5/27
Y1 - 2010/5/27
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
KW - Embryonic tissue
KW - Fibroblasts
KW - Xeno-transplantation
UR - http://www.scopus.com/inward/record.url?scp=77952868351&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3181d720fd
DO - 10.1097/TP.0b013e3181d720fd
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C2 - 20195218
AN - SCOPUS:77952868351
SN - 0041-1337
VL - 89
SP - 1198
EP - 1207
JO - Transplantation
JF - Transplantation
IS - 10
ER -