TY - JOUR
T1 - Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells
AU - Maeda, Keiko
AU - Enomoto, Atsushi
AU - Hara, Akitoshi
AU - Asai, Naoya
AU - Kobayashi, Takeshi
AU - Horinouchi, Asuka
AU - Maruyama, Shoichi
AU - Ishikawa, Yuichi
AU - Nishiyama, Takahiro
AU - Kiyoi, Hitoshi
AU - Kato, Takuya
AU - Ando, Kenju
AU - Weng, Liang
AU - Mii, Shinji
AU - Asai, Masato
AU - Mizutani, Yasuyuki
AU - Watanabe, Osamu
AU - Hirooka, Yoshiki
AU - Goto, Hidemi
AU - Takahashi, Masahide
N1 - Funding Information:
We thank Kinji Ohno and Bisei Ohkawara (Nagoya University) for providing the Sox9 reporter plasmid, Shigeki Higashiyama (Ehime University) for providing the plasmids encoding the ErbB family members, and Akihiko Matsumine (Mie University) for providing the Decorin expression plasmid. We thank Makoto Ikeya, Yonghui Jin and Hidetoshi Sakurai (CiRA, Kyoto University), Akihito Yamamoto, Naotake Tsuboi and Mikito Takefuji (Nagoya University), Nobuhisa Nakamura (Aichi Gakuin University), Atsushi Masamune (Tohoku University), Akiyoshi Hoshino (Tokyo Metropolitan Police Hospital), and Katsuhiro Kato (Max Plank Institute for Melecular Biomedicine) for helpful discussion. We also thank Minoru Tanaka, Kaori Ushida and Kozo Uchiyama (Nagoya University) for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research (S) (to M.T.) and Grant-in-Aid for Young Scientists (A) (to A.E.) commissioned by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2016/2/29
Y1 - 2016/2/29
N2 - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo.
AB - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo.
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U2 - 10.1038/srep22288
DO - 10.1038/srep22288
M3 - Article
C2 - 26924503
AN - SCOPUS:84959336177
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 22288
ER -