Mizokami Tomomi, Hisha Hiroko, Okazaki Satoshi, Takaki Takashi, Wang Xiao-Li, Song Chang-Ye, Li Qing, Kato Junko, Hosaka Naoki, Inaba Muneo, Kanzaki Hideharu, Ikehara Susumu
First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka, Japan.
Haematologica. 2009 May;94(5):618-28. doi: 10.3324/haematol.2008.004705. Epub 2009 Mar 31.
We previously found in a murine hematopoietic system that hematopoietic stem cells show high differentiation and proliferation capacity on bone marrow-derived mesenchymal stem cells/stromal cells (microenvironment) with "self" major histocompatibility complex (MHC).
We examined whether amnion-derived adherent cells have the characteristics of mesenchymal stem cells, and whether these adherent cells can support the proliferation of umbilical cord blood-derived lineage-negative and CD34-positive cells (Lin(-)CD34(+) cells) obtained from the same fetus to a greater extent than those derived from other fetuses.
Culture-expanded amnion-derived adherent cells expressed mesenchymal stem cell markers and HLA-ABC molecules and could differentiate into osteoblasts, adipocytes and chondrocyte-like cells, indicating that the cells have the characteristics of mesenchymal stem cells. The Lin(-)CD34(+) cells purified from the frozen umbilical cord blood were strongly positive for HLA-ABC, and contained a large number of hematopoietic stem cells. When the Lin(-)CD34(+) cells were cultured on the autologous (MHC-matched) or MHC-mismatched amnion-derived adherent cells in short-term assays (hematopoietic stem cell-proliferation) and long-term culture-initiating cell assays, greater expansion of the Lin(-)CD34(+) cells was observed in the MHC-matched combination than in MHC-mismatched combinations. The concentration of granulocyte-macrophage colony-stimulating factor in the culture supernatants of the long-term culture-initiating cell assays was significantly higher in the MHC-matched combination than in MHC-mismatched combinations.
IT is likely that a MHC restriction exists between hematopoietic stem cells and mesenchymal stem cells/stromal cells in the human hematopoietic system and that granulocute-macropage colony-stimulating factor contributes to some extent to the preferential hematopoiesis-supporting ability of the MHC-matched amnion-derived adherent cells.
我们先前在小鼠造血系统中发现，造血干细胞在具有“自身”主要组织相容性复合体（MHC）的骨髓间充质干细胞/基质细胞（微环境）上表现出高分化和增殖能力。
我们检测了羊膜来源的贴壁细胞是否具有间充质干细胞的特征，以及这些贴壁细胞是否能比来自其他胎儿的贴壁细胞更有效地支持从同一胎儿获得的脐带血来源的谱系阴性和CD34阳性细胞（Lin(-)CD34(+)细胞）的增殖。
培养扩增的羊膜来源贴壁细胞表达间充质干细胞标志物和HLA-ABC分子，并能分化为成骨细胞、脂肪细胞和软骨样细胞，表明这些细胞具有间充质干细胞的特征。从冷冻脐带血中纯化的Lin(-)CD34(+)细胞HLA-ABC呈强阳性，且含有大量造血干细胞。当在短期试验（造血干细胞增殖）和长期培养起始细胞试验中，将Lin(-)CD34(+)细胞培养在自体（MHC匹配）或MHC不匹配的羊膜来源贴壁细胞上时，与MHC不匹配组合相比，在MHC匹配组合中观察到Lin(-)CD34(+)细胞有更大程度的扩增。在长期培养起始细胞试验的培养上清液中，MHC匹配组合中的粒细胞-巨噬细胞集落刺激因子浓度显著高于MHC不匹配组合。
在人类造血系统中，造血干细胞与间充质干细胞/基质细胞之间可能存在MHC限制，并且粒细胞-巨噬细胞集落刺激因子在一定程度上有助于MHC匹配的羊膜来源贴壁细胞优先支持造血的能力。
