Circulating Connective Tissue Precursors: Extreme Rarity in Humans and Chondrogenic Potential in Guinea Pigs
Article first published online: 26 APR 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 7, pages 1830–1839, July 2007
How to Cite
Kuznetsov, S. A., Mankani, M. H., Leet, A. I., Ziran, N., Gronthos, S. and Robey, P. G. (2007), Circulating Connective Tissue Precursors: Extreme Rarity in Humans and Chondrogenic Potential in Guinea Pigs. STEM CELLS, 25: 1830–1839. doi: 10.1634/stemcells.2007-0140
- Issue published online: 2 JAN 2009
- Article first published online: 26 APR 2007
- Manuscript Accepted: 19 APR 2007
- Manuscript Received: 22 FEB 2007
- Blood cells;
- Cell culture;
- Cell transplantation;
Using a variety of cell separation techniques and cultivation conditions, circulating, adherent, connective tissue, clonogenic cells were found in just 3 donors out of 66, demonstrating that these precursors are extremely rare in postnatal human blood. Contrary to humans, guinea pig blood shows much more reproducible connective tissue colony formation; it was therefore chosen to study the differentiation potential of adherent blood-derived clonogenic cells. Out of 22 single colony-derived strains of various morphologies, only 5 spindle-shaped strains showed extensive proliferative capacity in vitro. None of these strains formed bone upon in vivo transplantation, whereas two strains formed cartilage in high-density pellet cultures in vitro. Both chondrogenic strains included cells expressing aggrecan, whereas nonchondrogenic strains did not. Out of four polyclonal strains studied, one formed both cartilage and abundant bone accompanied by hematopoiesis-supporting stroma. Evidently, there are cells in adult guinea pig blood capable of both extensive proliferation and differentiation toward cartilage: circulating chondrogenic precursors. Although some of these cells lack osteogenic potential and therefore represent committed chondrogenic precursors, others may be multipotential and consequently belong to the family of skeletal stem cells. This is the first demonstration of postnatal circulating chondrogenic precursors, as well as of precursor cells with chondrogenic but not osteogenic potential.
Disclosure of potential conflicts of interest is found at the end of this article.