Drs. Goldstein and Drukker contributed equally to this work.
Integration and differentiation of human embryonic stem cells transplanted to the chick embryo
Article first published online: 19 JUL 2002
Copyright © 2002 Wiley-Liss, Inc.
Volume 225, Issue 1, pages 80–86, September 2002
How to Cite
Goldstein, R. S., Drukker, M., Reubinoff, B. E. and Benvenisty, N. (2002), Integration and differentiation of human embryonic stem cells transplanted to the chick embryo. Dev. Dyn., 225: 80–86. doi: 10.1002/dvdy.10108
- Issue published online: 26 AUG 2002
- Article first published online: 19 JUL 2002
- Manuscript Accepted: 11 JUN 2002
- Manuscript Received: 1 MAR 2002
- The Herbert Cohn Chair
- The Aviv Fund for Neuroscience Research
- The Health Science Center at Bar-Ilan University
- human ES cells;
- neural rosettes;
- transplantation therapy;
- human embryogenesis;
- neuronal differentiation
Human embryonic stem (ES) cells are pluripotent cells that can differentiate into a large array of cell types and, thus, hold promise for advancing our understanding of human embryology and for contributing to transplantation medicine. In this study, differentiation of human ES cells was examined in vivo by in ovo transplantation to organogenesis-stage embryos. Colonies of human ES cells were grafted into or in place of epithelial-stage somites of chick embryos of 1.5 to 2 days of development. The grafted human ES cells survived in the chick host and were identified by vital staining with carboxyfluorescein diacetate or use of a green fluorescent protein–expressing cells. Histologic analysis showed that human ES cells are easily distinguished from host cells by their larger, more intensely staining nuclei. Some grafted cells differentiated en masse into epithelia, whereas others migrated and mingled with host tissues, including the dorsal root ganglion. Colonies grafted directly adjacent to the host neural tube produced primarily structures with the morphology and molecular characteristics of neural rosettes. These structures contain differentiated neurons as shown by β-3-tubulin and neurofilament expression in axons and cell bodies. Axons derived from the grafted cells penetrate the host nervous system, and host axons enter the structures derived from the graft. Our results show that human ES cells transplanted in ovo survive, divide, differentiate, and integrate with host tissues and that the host embryonic environment may modulate their differentiation. The chick embryo, therefore, may serve as an accessible and unique experimental system for the study of in vivo development of human ES cells. © 2002 Wiley-Liss, Inc.