Effects of allogenic bone marrow mesenchymal stem cell alone, or combined with growth factor transplantation on rabbit cardiac function after myocardial infarction

Zhuo LI; Tianxiang GU; Yuhai ZHANG

ABSTRACT

BACKGROUND:

Bone marrow mesenchymal stem cells(BMSCs) have the potential to differentiate into various cells and growth factor plays a key role in cell engraftment, survival, and differentiation.

OBJECTIVE:

To observe the effects of hepatocyte growth factor(HGF) and insulin-like growth factor(IGF) combined with stem cell transplantation on cardiac function in rabbits after myocardial infarction.DESIGN, TIME AND

SETTING:

The randomized controlled animal study was performed at the Animal Experimental Center, China Medical University from November 2006 to March 2008.MATERIALSA total of 28 healthy adult rabbits, of both genders, weighing 2.0-2.5 kg were used in this study.

METHODS:

Rabbit BMSCs were cultured in vitro.The left anterodecendant arteries(LAD) of adult rabbits were ligated to establish animal models of myocardial infarction by a 60-min occlusion of the LAD, followed by reperfusion.A total of 28 adult rabbits were equally and randomly assigned into 4 groups.In the combination group, rabbit models were injected with 8 ?L DMEM, supplemented with 5?1011/L BMSCs 40 ?L, 150 ?g/L HGF and 200 ?g/L IGF-1 at 3 days following model induction.In the stem cell group, rabbit models were infused with 5?1011/L BMSCs 40 ?L.In the growth factor group, rabbit models were injected with 8 ?L DMEM containing 150 ?g/L HGF and 200 ?g/L IGF-1.In the control group, rabbit models were treated with the same volume of DMEM.Three dimensional(3D) full volume image of the left ventricle was measured by IE33 model ultraphonic apparatus with 3D detecting head.MAIN OUTCOME

MEASURES:

The following parameters were measuredresults of BMSC fluorescent labeling, end diastolic dimension, end systolic volume and ejection fraction of the left ventricle in each group at 6 weeks following model induction.

RESULTS:

A total of 28 adult rabbits were included in the final analysis.BMSCs adhered, with various morphology.Following 1 week, adhered cells gradually formed cell colony, with the presence of spindle-shape.At 2 weeks, about 80%-90% cells were confluent.Under a fluorescence microscope, DAPI-positive cells were found in the combination and stem cell groups.Positive cells were scattered in the rabbit myocardium, and surrounding the scar, along cardiac muscle fiber direction.Compared with the control and growth factor groups, cardiac function was significantly improved in the combination and stem cell groups(P