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© The Rockefeller University Press, 0022-1007/1999/5/1601/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1601-1610

Articles

Identification of Lymphomyeloid Primitive Progenitor Cells in Fresh Human Cord Blood and in the Marrow of Nonobese Diabetic–Severe Combined Immunodeficient (NOD-SCID) Mice Transplanted with Human CD34+ Cord Blood Cells

Catherine Robin, Françoise Pflumio, William Vainchenker, and Laure Coulombel

From the Institut National de la Santé et de la Recherche Médicale U 362, Institut Gustave Roussy, 94800 Villejuif, France

Transplantation of genetically marked donor cells in mice have unambiguously identified individual clones with full differentiative potential in all lymphoid and myeloid pathways. Such evidence has been lacking in humans because of limitations inherent to clonal stem cell assays. In this work, we used single cell cultures to show that human cord blood (CB) contains totipotent CD34+ cells capable of T, B, natural killer, and granulocytic cell differentiation. Single CD34+ CD19–Thy1+ (or CD38–) cells from fresh CB were first induced to proliferate and their progeny separately studied in mouse fetal thymic organotypic cultures (FTOCs) and cocultures on murine stromal feeder layers. 10% of the clones individually analyzed produced CD19+, CD56+, and CD15+ cells in stromal cocultures and CD4+CD8+ T cells in FTOCs, identifying totipotent progenitor cells. Furthermore, we showed that totipotent clones with similar lymphomyeloid potential are detected in the bone marrow of nonobese diabetic severe combined immunodeficient (NOD-SCID) mice transplanted 4 mo earlier with human CB CD34+ cells. These results provide the first direct demonstration that human CB contains totipotent lymphomyeloid progenitors and transplantable CD34+ cells with the ability to reconstitute, in the marrow of recipient mice, the hierarchy of hematopoietic compartments, including a compartment of functional totipotent cells. These experimental approaches can now be exploited to analyze mechanisms controlling the decisions of such primitive human progenitors and to design conditions for their ampification that can be helpful for therapeutic purposes.

Key Words: stem cells • fetal thymic organotypic culture • nonobese diabetic-severe combined immunodeficient • lymphopoiesis • hematopoiesis

Address correspondence to Laure Coulombel, INSERM U 362, Institut Gustave Roussy, 39 Av Camille Desmoulins, 94800 Villejuif, France. Phone: 33-1-42-11-42-33; Fax: 33-1-42-11-52-40; E-mail: laurec{at}igr.fr

C. Robin and F. Pflumio contributed equally to this work.

This work was presented in part at the International Society for Experimental Hematology meeting, Vancouver, Canada, August 1998, and published in abstract form (Robin, C., F. Pflumio, C. Tourino, and L. Coulombel. 1998. Exp. Hematol. 26:693).

Abbreviations used: CB, cord blood; DP, double positive; FTOCs, fetal thymic organotypic cultures; Gr/M, granulomonocytic; MGDF, megakaryocyte growth and differentiation factor; NOD, nonobese diabetic; PEG, pegylated; rhu, recombinant human; SCF, stem cell factor.


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