Effect of myoblast carrying insulin-like growth factor 1 on healing of tibial fracture in mice

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Abstract

BACKGROUND:

With the development of gene therapy, it is feasible to transplant cells carrying insulin-like growth factor 1 (IGF-1) gene into the injury area in order to continuously express this gene in vivo and to treat bone nonunion and delayed healing in the fracture patients.

OBJECTIVE:

To observe the effects of myoblasts carrying IGF-1 gene injected into the mice on the healing of tibial fracture.

DESIGN, TIME AND SETTING:

Randomized control animal experiment was performed in the Shantou University Medical College between January 2007 and April 2008.

MATERIALS:

A total of 42 male C57BL/6J mice of 8 weeks old, weighing 22-25 g, were used to establish fracture in left tibial bone.

METHODS:

Forty-two model mice were divided into two groups by random with 21 mice in each. Experimental animals were injected with 0.3 mL myoblast suspension carrying IGF-1 gene into the muscle surrounding fracture site, while control animals were injected with 0.3 mL saline solution. Seven mice in each group were executed at 2, 3, 4 weeks after operation, the bone callus were stained by hematoxylin-eosin.

MAIN OUTCOME MEASURES:

Quantitative analysis of the formed callus area and the relative amounts of components; exogenous cells' survival and the expression of IGF-1; bone mineral density and bony callus cellular growth.

RESULTS:

①In the experiment group, the BrdU staining and IGF-1 immunohistochemistry in mice transplanted with myoblasts were positive. The average grey value at 4 weeks was slightly higher than that at 2 weeks in the experiment group, but no significant difference was found (P > 0.05). ②The transplanted myoblasts carrying IGF-1 gene could survive for more than 4 weeks in the muscle surrounding fracture site, they were shown to stably express human IGF-1. ③The percent of trabecular bone on the total area of bony callus in the experimental group was greater than that in the control group at each period following modeling, and the difference at 3 and 4 weeks post-surgery demonstrated statistical significance by F test (P < 0.05). At 4 weeks, the bone mineral density in bony callus area of the experimental group was higher than that of control group (P < 0.05). ④ Transmission electron microscope observation showed the experimental group was better than the controls in the quantity of generated cells in bone, the degree of active, the number and distribution of collagen.

CONCLUSION:

Local injection of myoblasts carrying human IGF-1 gene may promote the healing of tibial fracture in C57BL/6J mice.

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