Complement-dependent control of teratoma formation by embryonic stem cells.
The fetus has pluripotent stem cells that when transferred to mature individuals can generate tumors. However, for reasons yet unknown, tumors form rarely in the fetus and/or the mother during normal gestation. We questioned whether the complement system might protect against tumor formation by pluripotent stem cells. Murine embryonic stem cells were notably more susceptible than cardiomyocytes differentiated from those cells to lysis by complement in heterologous and homologous sera. Treatment of embryonic stem cells with heterologous serum averted tumor formation after residual cells were transplanted into mice. Confirming the importance of homologous complement in preventing formation of tumors, untreated embryonic stem cells formed tumors more quickly in C3-deficient than in wild-type mice. Susceptibility of embryonic stem cells to complement required an intact alternative pathway and was owed at least in part to a relative deficiency of sialic acid on cell surfaces compared with differentiated cells. Susceptibility to complement and resistance to tumors was inversely related to the number of cells transferred. These findings show that formation of tumors from embryonic stem cells is controlled in part by the alternative pathway of complement and suggest that susceptibility to complement might represent a general property of pluripotent stem cells that can be exploited to prevent tumor formation.
Koch
Cody A
CA
Transplantation Biology, Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, NY 55905, USA.
Jordan
Corinne E
CE
Platt
Jeffrey L
JL
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000502:physiology*; D004622:Embryo, Mammalian; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011951:Receptors, Complement / Q000096:biosynthesis; D017463:Receptors, Complement 3b; D033581:Stem Cell Transplantation; D013724:Teratoma; D051996:Transcription Factor RelA
D002352:Carrier Proteins; C081470:Cr1l protein, mouse; D009363:Neoplasm Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C498144:Rela protein, mouse; D051996:Transcription Factor RelA