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 Blood, 15 February 2008, Vol. 111, No. 4, pp. 2436-2443.
Prepublished online as a Blood First Edition Paper on November 28, 2007; DOI 10.1182/blood-2007-07-099333.

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STEM CELLS IN HEMATOLOGY

Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos

Xiao-Yan Wang1, Yu Lan2, Wen-Yan He1, Lei Zhang3, Hui-Yu Yao1, Chun-Mei Hou1, Ying Tong3, Yuan-Lin Liu1, Guan Yang2, Xiao-Dan Liu1, Xiao Yang2, Bing Liu1, and Ning Mao1

1 Department of Cell Biology, Institute of Basic Medical Sciences, Beijing; 2 Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing; and 3 Department of Gynecology and Obstetrics, Air Force General Hospital, Beijing, China

Mesenchymal stem cells (MSCs) are multipotent stem cells that can generate various microenvironment components in bone marrow, ensuring a precise control over self-renewal and multilineage differentiation of hematopoietic stem cells. Nevertheless, their spatiotemporal correlation with embryonic hematopoiesis remains rudimentary, particularly in relation to the human being. Here, we reported that human aorta-gonad-mesonephros (AGM) resided with bona fide MSCs. They were highly proliferative as fibroblastoid population bearing uniform surface markers (CD45–, CD34–, CD105+, CD73+, CD29+, and CD44+), expressed pluripotential molecules Oct-4 and Nanog, and clonally demonstrated trilineage differentiation capacity (osteocytes, chondrocytes, and adipocytes). The frequency and absolute number of MSCs in aorta plus surrounding mesenchyme (E26-E27) were 0.3% and 164, respectively. Moreover, they were functionally equivalent to MSCs from adult bone marrow, that is, supporting long-term hematopoiesis and suppressing T-lymphocyte proliferation in vitro. In comparison, the matching yolk sac contained bipotent mesenchymal precursors that propagated more slowly and failed to generate chondrocytes in vitro. Together with previous knowledge, we propose that a proportion of MSCs initially develop in human AGM prior to their emergence in embryonic circulation and fetal liver.


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