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Complement-Dependent Control of Teratoma Formation by Embryonic Stem Cells¹

Cody A. Koch^*,, Corinne E. Jordan^*, and Jeffrey L. Platt^2,*,,,

^* Transplantation Biology, Department of Immunology, Department of Surgery, and Department of Pediatrics, Mayo Clinic College of Medicine, Rochester, MN 55905

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant HL52297 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Jeffrey L. Platt, Transplantation Biology, Medical Sciences Building 2-66, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905. E-mail address: platt.jeffrey{at}mayo.edu

³ Abbreviation used in this paper: PIPLC, phosphatidylinositol-specific phospholipase C.