[Treatment of acute myocardial infarction with autologous bone marrow stem cells mobilization combined with recombinant growth factor in rat].
OBJECTIVE
To observe the regeneration cardiomyocytes and neovascularization after mobilizing autologous bone marrow stem cells by granulocyte colony stimulating factor (G-CSF) alone or G-CSF combined with recombinant human growth hormone (rhGH) in Wistar rats with acute myocardial infarction (AMI).


METHODS
AMI rat model was reproduced by liquid nitrogen cryoinjury. The rats were randomly divided into six groups: mobilization group (N group, n=8), sham operation group (SO group, n=6), myocardial infarction group (MI group, n=8), G-CSF group (G group, n=8), rhGH group (GH group, n=8) and G-CSF combined with rhGH group (GG group, n=8). White blood cell (WBC) count and mononuclear cells proportion (MNC%) in peripheral blood were determined with ABX blood cell analyzer to estimate bone marrow stem cells mobilization. Four weeks after intervention, the rats were sacrificed, their respective body and heart weight were obtained, and the hearts were harvested for hematoxylin and eosin (HE) and immunohistochemical examination.


RESULTS
(1)Comparing with baseline values, after 6 days administration of G-CSF, the WBC and MNC% increased in N and G groups (both P<0.01); WBC increased (P<0.01) but no difference of MNC% in MI group (P>0.05); WBC and MNC% were significantly higher in G group than those in MI group (all P<0.05). (2)Body and heart weights in GH and GG groups were higher than those in SO, MI and G groups respectively (all P<0.05). The ratio of heart and body weight was higher in GC group than that in MI,G and SO groups (P<0.05). (3)There were no significant differences in infarct size among MI, G, GH, and GG groups (P>0.05). (4)The capillary densities were higher in G, GH and GG groups than those in MI and SO groups; the density in GG group was higher than that in G and GH groups (all P<0.01). (5)BrdU positively stained neonatal cells were observed in G, GH and GG groups. Of them some developed into the endothelial cells. BrdU and cTnI double positive stained cells were observed in G and GG groups, which implied these cells might have differentiated into cardiac myocyte like cells.


CONCLUSIONS
(1)G-CSF can mobilize bone marrow stem cells into peripheral blood in normal and cardiac infarct rats. The mobilized stem cells may enter into the infarct zone and induce the regeneration of cardiac myocyte like cells and vascular endothelial cells. (2)rhGH may promote the regeneration of capillary in the zone of infarction, but does not induce regeneration of cardiac myocyte like cells. (3)The combination of G-CSF with rhGH might promote more capillary regeneration than either of them used alone.
Liu
Ke-qiang
KQ
Tianjin People's Hospital, Tianjin 300121, China. kentliu999@sohu.com
Qi
Xin
X
Du
Jian-ping
JP
Cheng
Li-song
LS
Yang
Wen-ling
WL
Li
Yan
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D019382:Human Growth Hormone / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D019382:Human Growth Hormone; D016179:Granulocyte Colony-Stimulating Factor