Identification of a novel population of human cord blood cells with hema-topoietic and chondrocytic potential.
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.
Jay
Karen E
KE
Stem Cell Biology and Regenerative Medicine, The John P. Robarts Research Institute, 100 Perth Drive, London, Ontario, N6A 5K8, Canada.
Rouleau
Anne
A
Underhill
T Michael
TM
Bhatia
Mickie
M
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D001755:Blastocyst / Q000166:cytology / Q000502:physiology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D018878:Limb Buds / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018183:Transplantation Chimera / Q000502:physiology
D018952:Antigens, CD34; C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017493:Leukocyte Common Antigens