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

Abstract

Mesenchymal stem cells (MSCs IntroductionMesenchymal stem cells (MSCs) are defined as a group of multipotent stem cells that can functionally differentiate into at least bone, fat, and cartilage in vitro and in vivo. [1][2][3][4][5][6][7][8] Under appropriate culture conditions, MSCs are readily amplified in vitro for several passages without signs of senescence and differentiation. The 2 properties render them as an intriguing source in cell therapy and tissue engineering. MSCs were first documented by Friedenstein et al at an extremely low frequency within the bone marrow (BM), a canonical reservoir for a variety of stem cells. 1 Functionally, the self-renewal and differentiation of hematopoietic stem cells (HSCs) are tightly and precisely regulated by the marrow stromal milieu, a complex cellular network composed of the descendents of MSCs. For example, osteoblasts lining the bone surface can modulate the HSC expansion via Notch signaling pathway or N-cadherin/␤-catenin adherens complex in vitro and in vivo. 9,10 The MSC, itself, can also modulate hematopoiesis in vitro through secreting a set of hematopoietic cytokines and intercellular contact. 11,12 Systemic administration of adult or fetal tissue-derived MSCs promotes the homing and engraftment of HSCs in vivo by unknown mechanisms. [13][14][15][16] Despite of our increasing understanding of MSCs in adult hematopoiesis, little is known about their developmental origin and correlation with strikingly changing blood-forming sites during embryogenesis, particularly in the human being. 17 The first wave of hematopoiesis in humans is initiated during the third week in the extraembryonic yolk sac (YS), characterized by the production of nucleated erythrocytes in situ. 18,19 As is the case in other higher vertebrates, the second wave is characterized by de novo generation of HSCs in the intraembryonic P-Sp/AGM, followed by migration and colonizing downstream fetal liver for further maturation and amplification. [20][21][22][23] Campagnoli et al claim that human MSCs appear first in fetal blood at the seventh week, and later in the fetal liver and bone marrow from the 10th week. 24 Recently, Mendes et al reported that the mesenchymal progenitors are exclusively allocated in the mouse AGM. 25 However, the ontogeny of human MSCs in the embryonic hematopoietic tissues remains unknown.Herein, we found that human AGM region served as a potent niche for embryonic MSCs that were roughly identical to the bone marrow regarding general morphology, immunophenotype, triple differentiation capacity, and immunobiologic feature. The expression of pluripotential-related markers (Oct-4 and Nanog) and the hematopoietic supportive activity in AGM-derived MSCs corroborated their development stage and anatomic location. Methods Human samplesEighteen human embryos at 25 to 40 days of development were obtained immediately after voluntary terminations of pregnancy induced with the RU 486 antiprogestative compound. Human tissue collection for research purpose was approved by Research Eth...

Migration of dorsal aorta mesenchymal stem cells induced by mouse embryonic circulation

“…First, our result was different from previous results that mouse primary adherent cells derived from the E11 DA region lack the ability to differentiate into adipose lineage (Mendes et al, 2005). The DA-MSCs of mouse possessed the same adipogenic potential as those of human being, confirmed by oil red-O staining and specific adipogenic gene expression (Wang et al, 2008). Actually, the mouse DA-derived CFU-F clones varied quite differently in their adipogenic differentiation capacity.…”

“…In this study, the MSCs isolated from the compact bone of 3-week-old mouse were used as the positive control. The cells dissociated from E11.5 DA were cultured in the growth medium used for human AGM-MSCs with some modifications (Wang et al, 2008). As fetal bovine serum (FBS) is critical for in vitro proliferation of mouse MSCs, 10 (Hyclone) and 4 (Stem Cell Technologies) batches of FBS were screened among which 1 lot was selected.…”

“…Characterization of adipocytes was performed by Oilred-O staining and by assessing adipogenic specific gene expression (Wang et al, 2008).…”

Hematopoietic Microenvironment in the Fetal Liver: Roles of Different Cell Populations

“…In the course of embryonic development, MSC supposedly migrate to the liver from the aortic-gonad-mesonephros region [64], although their de novo formation from the septum transversum mesenchyme is also possible. The amount of these cells in the liver changes during development in correlation with hematopoietic activity [65][66][67], which is evidence for their important role in organization of the hematopoietic microenvironment.…”

Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells

“…MSCs were raised from the aortagonad-mesonephros (AGM), 17 placental tissue, umbilical cord artery and vein as well as from bone marrow (BM) fat and mononuclear cells (MNCs). Like bona fide MSCs, 18,19 all obtained stromal cells expressed the cell surface antigens CD44, CD73, CD90, CD105 and CD146, were negative for CD14, CD31, CD34 and CD45 ( Fig.…”