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TISSUE-SPECIFIC STEM CELLS

Circulating Connective Tissue Precursors: Extreme Rarity in Humans and Chondrogenic Potential in Guinea Pigs

Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

Key Words. Blood cells • Cell culture • Cell transplantation • Chondrogenesis

Correspondence: Sergei A. Kuznetsov, Ph.D., National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 228, 30 Convent Dr. MSC 4370, Bethesda, Maryland 20892-4370, USA. Telephone: 301-402-2476; Fax: 301-402-0824; e-mail: skuznets{at}mail.nih.gov

Received on February 22, 2007; accepted for publication on April 19, 2007.

First published online in STEM CELLS EXPRESS  April 26, 2007.


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.

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