[Activation of auto-mesenchymal stem cells of skeletal muscle by bone morphogenetic protein for rescuing bone marrow failure].
OBJECTIVE
To explore the effect of bone morphogenetic protein (BMP) to activate mesenchymal stem cells of skeletal muscle for rescuing bone marrow failure.


METHODS
The study was performed on lethal rat acute aplastic anemia model induced by combined 5-fluorouracil (5-FU) and busulfan. The rh-BMP-2 was implanted into the thigh muscle of the rats at 3 days before aplastic anemia was induced. In the control group the rats were implanted with agar into the thigh muscle. The blood picture, pathologic changes and the mortality in two groups were observed. At the same time, rh-BMP-2 were implanted into the thigh muscle of normal Kun-min mice for dynamic control observation of the implantation local morphological changes, colony forming units-spleen (CFU-S) and stem cell growth factor (SCF) expression of the stroma cells of ectopic ossicles induced by BMP.


RESULTS
At 7 days after BMP implantation in the mice the mesenchymal cells around BMP in muscle proliferated, and appeared in bone marrow to form an ectopic ossicles. The SCF expression of stroma cells in ectopic ossicles were higher than that of self-bone marrow. 56.3% of BMP-treated aplastic rats were survived over 3 months and its hematopoiesis was completely reconstituted and the histo-morphological picture of the spleen and bone marrow were recovered to normal. But in the control group only one of 23 rats was survived, the remainder died of hematopoietic failure.


CONCLUSIONS
BMP-implantation into the skeletal muscle could rescue the bone marrow hematopoietic failure. The mechanism might be related to the BMP activated auto-mesenchymal cells of skeletal muscles to direct hematopoietic cell differentiation. In our hands it might create a new pathway for utilization of auto-muscle derived mesenchymal cells to reconstitute hematopoiesis.
Chu
Jian-xin
JX
National Lab. of Experimental Hematology, Institute of Hematology, CAMS and PUMC, Tianjin, 300020, China. chujianxin@hotmail.com
Zhao
Jun-ming
JM
Ding
Shun-li
SL
Xu
Shi-cai
SC
Liu
Ai-ru
AR
Wang
Shu-ping
SP
D000741:Anemia, Aplastic / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D002066:Busulfan; D002454:Cell Differentiation; D005260:Female; D005472:Fluorouracil; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D020007:Implants, Experimental; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D013234:Stem Cells / Q000166:cytology
D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D002066:Busulfan; D005472:Fluorouracil