REGULAR ARTICLES

Cell Research (2004); 14(4):268-282

Identification of a novel population of human cord blood cells with hema-topoietic and chondrocytic potential

Karen E JAY^1,2, Anne ROULEAU¹, T Michael UNDERHILL³, Mickie BHATIA^1,2,3,*

¹Stem Cell Biology and Regenerative Medicine, The John P. Robarts Research Institute, 100 Perth Drive, London, Ontario, N6A 5K8, Canada.
²Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
³Department of Physiology, The University of Western Ontario, London, Ontario, Canada.

Received,  Apr 5, 2004  Revised, May 19, 2004   Accepted, May 24, 2004

Correspondence: Mickie BHATIA (519) 663-5777 Ext. 34166 (phone) (519) 663-2982 (fax) mbhatia@robarts.ca

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With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin^-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin^-CD45^- cells also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin^-CD45^-CD34^- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin^-CD45^-CD34^- differentiation into chondrocytes. Moreover, unlike CD34⁺ human hematopoietic stem cells, Lin^-CD45^-CD34^- cells were unable to proliferate or survive in liquid cultures, whereas single Lin^-CD45^-CD34^- cells were able to chimerize the inner cell mass (ICM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin^-CD45^-CD34^- cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.

Keywords: hematopoietic, chondrocyte, CD45, embryonic.