Remote intramuscular injection of amniotic fluid stem cells in myocardial infarction mouse model
Date Issued
2012
Date
2012
Author(s)
Tseng, Tse-Yang
Abstract
Heart diseases have been one of the major causes of death in Taiwan for years. Myocardial infarction (MI) is the best-known case among heart diseases, and often causes cell death in ischemic area, results in pathological remodeling and decreasing cardiac function, even may leads to heart failure eventually. Stem cell therapy had been demonstrated that could repair damaged heart through differentiation potential and factors secreting of stem cells. Amniotic fluid stem cells (AFSCs) among stem cells can be obtained with low-invasively procedure, and possess immunosuppressive properties, and shows cardiomyoplasticity in vivo and in vitro. Previous studies showed transplantation of AFSCs has beneficial effects for MI animals, but studies focused on its secretion abilities still lacks. Hence, the aims of this study are to investigate their therapeutic potential on MI mice by using the manner of AFSCs intramuscular injection.
In order to test the therapeutic potential of factors released by AFSCs, porcine AFSCs were isolated from amniotic fluid of E70 porcine fetus of Ds-red-transgenic pig. These cells express surface antigen CD44 and slight express CD90, do not express CD4a, CD31, and can stably express red fluorescence protein (RFP) after serial passage.
Before starting to test the therapeutic potential of AFSCs, appropriate MI model needs to be established. For this purpose, 8-week-old male C57/B6 mice were divided into MI group and Sham group. MI was induced by ligation of the left descending coronary. Four weeks after surgery, both of left ventricular (LV) end-systolic dimension and LV end-diastolic dimension increased significantly in MI group (p < 0.05). Two weeks after surgery, ejection fraction in MI group decreased to 47.82 ± 2.21%, and then further decreased to 35.51 ± 4.13% two weeks later. In addition, wall thickness decreased in infracted region, and fibrosis scar has formed within injury sites. Above results indicated suitable MI model has been established.
In order to test the effects of AFSCs intramuscular injection on MI mice, MI model mice were divided into 3 groups: medium cell dose (1 x 106 cells per leg) group Cell-M, high cell dose (4 x 106 cells per leg) group Cell-H and PBS group. Cells or PBS were directly injected into hamstring muscle 20 minutes after MI surgery. Four weeks after MI surgery, Cell-M and Cell-H groups (43.16 ± 2.81%, 50.04 ± 5.37%) when compared with PBS group (37.54 ± 3.98%) preserved significantly better LV ejection fraction (p < 0.05). And the ejection fraction in Cell-M and Cell-H groups four weeks after MI persevered in same level when compared to two weeks after MI. Infarct scar sizes in both Cell-M and Cell-H groups were smaller than in PBS group. Wall thickness in scar region preserved thicker in Cell-M and Cell-H groups when compared with PBS group. Cell-M and Cell-H groups also showed smaller LV expansion index, which indicated lower degree of LV dilation. The specimens of hamstring muscle, heart, lung, liver and kidney from mice in all groups were collected and detected by IVIS (in vivo imaging system) for RFP signals from injected or migrated cells. The result showed that only hamstring muscles from Cell-M and Cell-H groups exhibit RFP positive signals.
In summary, intramuscular injection of porcine AFSCs can reduce scar size, reduce pathological remodeling, and preserve better heart function after MI bearing. Putatively, intramuscularly injected AFSCs resided in hamstring muscle, and possibly assist recovery of heart morphology and function through their secreting factors.
Subjects
Myocardial infarction
Amniotic fluid stem cell
Ds-red transgenic pig
Cell transplantation
Type
thesis
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