TY - JOUR
T1 - In vivo and in vitro differentiation of myocytes from human bone marrow-derived multipotent progenitor cells
AU - Muguruma, Yukari
AU - Reyes, Morayma
AU - Nakamura, Yoshihiko
AU - Sato, Tadayuki
AU - Matsuzawa, Hideyuki
AU - Miyatake, Hiroko
AU - Akatsuka, Akira
AU - Itoh, Johbu
AU - Yahata, Takashi
AU - Ando, Kiyoshi
AU - Kato, Shunichi
AU - Hotta, Tomomitsu
N1 - Funding Information:
We thank Dr. Catherine Verfaillie for her valuable advice, Tamaki Saso and Tomoko Nakai for their excellent technical assistance, Drs. Tetsuro Tamaki and Hiroshi Kawada for helpful discussions, and all members of Research Center for Regenerative Medicine and Dr. Charles Peters for their support. This work is supported by a grant-in-aid for a Research Grant of the Science Frontier Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2003/12
Y1 - 2003/12
N2 - Objective. Recent studies have shown that bone marrow (BM) contains cells capable of differentiating into myocytes in vivo. However, addition of demethylation drugs has been necessary to induce myocyte differentiation from BM cells in vitro, and precise mechanisms of BM cells' conversion to myocytes and the origin of those cells have not been established. We investigated the expression of myogenic markers during differentiation and maturation of myocytes from BM-derived multipotent adult progenitor cells (MAPC) under physiological culture condition. Materials and Methods. Frozen BM samples from 21 healthy donors were used as a source of MAPC. To induce myocyte differentiation MAPC was cultured in the presence of 5% FCS, VEGF, bFGF, and IGF-1, and the expressions of myocyte markers were examined at various time points. We also investigated engraftment and differentiation of MAPC-derived myocytes in vivo. Results. Frozen BM-derived MAPC, cultured under the physiological myogenic condition, demonstrated spatial expression patterns of several myocyte markers similar to that of authentic myocyte differentiation. When injected into murine muscles, MAPC treated with the myogenic condition engrafted and differentiated into myocyte marker-positive cells and myotubes in vivo. Conclusion. For the first time, we were able to induce myocyte formation from BM cells under the physiological condition in vitro and demonstrated that treating cells with this condition prior to intramuscular injection increased efficiency of engraftment and differentiation in vivo.
AB - Objective. Recent studies have shown that bone marrow (BM) contains cells capable of differentiating into myocytes in vivo. However, addition of demethylation drugs has been necessary to induce myocyte differentiation from BM cells in vitro, and precise mechanisms of BM cells' conversion to myocytes and the origin of those cells have not been established. We investigated the expression of myogenic markers during differentiation and maturation of myocytes from BM-derived multipotent adult progenitor cells (MAPC) under physiological culture condition. Materials and Methods. Frozen BM samples from 21 healthy donors were used as a source of MAPC. To induce myocyte differentiation MAPC was cultured in the presence of 5% FCS, VEGF, bFGF, and IGF-1, and the expressions of myocyte markers were examined at various time points. We also investigated engraftment and differentiation of MAPC-derived myocytes in vivo. Results. Frozen BM-derived MAPC, cultured under the physiological myogenic condition, demonstrated spatial expression patterns of several myocyte markers similar to that of authentic myocyte differentiation. When injected into murine muscles, MAPC treated with the myogenic condition engrafted and differentiated into myocyte marker-positive cells and myotubes in vivo. Conclusion. For the first time, we were able to induce myocyte formation from BM cells under the physiological condition in vitro and demonstrated that treating cells with this condition prior to intramuscular injection increased efficiency of engraftment and differentiation in vivo.
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U2 - 10.1016/j.exphem.2003.09.003
DO - 10.1016/j.exphem.2003.09.003
M3 - Article
C2 - 14662341
AN - SCOPUS:10744225555
SN - 0301-472X
VL - 31
SP - 1323
EP - 1330
JO - Experimental Hematology
JF - Experimental Hematology
IS - 12
ER -