Editors' ChoiceStem Cells

The Teratoma Factory

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Science Translational Medicine  19 Dec 2012:
Vol. 4, Issue 165, pp. 165ec231
DOI: 10.1126/scitranslmed.3005490

Adult human skin cells can be reprogrammed to become pluripotent stem cells (iPSCs) by overexpressing a cocktail of four transcription factors. iPSCs show molecular and functional similarities to embryonic stem cells. They can be successfully differentiated into many cell types, including hematopoietic cells, but the yield of blood cells is inefficient. It is also not currently possible to generate hematopoietic stem cells (HSCs) from iPSCs. Now, Amabile et al. take a different approach by using iPSC-generated teratomas (a tumor containing derivatives of all three germ cell layers) to produce HSCs and other types of blood cells.

Amabile et al. generated iPSCs from adult human skin cells. The human iPSCs were able to differentiate in vitro into the three germ cell layers and to form teratomas when transplanted into immunodeficient mice. These teratomas contained bone marrow–like structures and blood cells such as neutrophils, lymphocytes, megakaryocytes, and HSCs. The human HSCs, B, T, and myeloid cells were able to migrate to the mouse bone marrow and spleen after transplantation. Hematopoiesis within the teratoma, especially HSC generation and migration, was enhanced when iPSCs were coinjected with OP9 stroma cells. The HSCs were able to form colony-forming unit (CFU)–GM and CFU-M in vitro and were able to engraft the bone marrow after transplantation into immunodeficient mice in the same way as cord blood cells. The transplanted recipient mice demonstrated multilineage reconstitution of the hematopoietic system, with a predominance of human myeloid cells. The teratoma-derived CD19+ B cells and CD3+ T cells were capable of producing fully human antibodies and cytokines, respectively.

This study shows that human hematopoietic cells derived from iPSC-generated teratomas are capable of multilineage reconstitution after transplantation into mice and can produce human antibodies and cytokines. These teratoma factories may be useful for producing therapeutic antibodies and for drug screening.

G. Amabile et al., In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood, published online 4 December 2012 (10.1182/blood-2012-06-434407). [Abstract]

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