Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering.

Chunlei Miao,Fanghong Yang,Tianyi Liu,Yingjie Zhang,Lufeng Tian,Wei Zhang,Lulu Zhou,Shengjian Tang,Fangjun Liu

doi:10.1155/2017/8619385

Abstract

Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious.

Highlights

Large segmental defects in craniofacial skeleton, those secondary to ablative surgery, trauma, or congenital defects, do not heal well and continue to present clinical challenges to the surgeon [1, 2]
Skeletal muscle has a propensity to form bone as seen most dramatically in the genetic disease fibrodysplasia ossificans progressiva (FOP) where patients develop a second skeleton as muscle spontaneously ossifies [9]
It is well known that muscle contains progenitors cells that can be recruited in situ for osteogenesis and fragments of muscle provide the functions of a space-filling scaffold when implanted, making skeletal muscle an ideal candidate for this novel bone regeneration strategy [10]

Summary

Introduction

Large segmental defects in craniofacial skeleton, those secondary to ablative surgery, trauma, or congenital defects, do not heal well and continue to present clinical challenges to the surgeon [1, 2]. Facilitated endogenous repair, an evolving discipline which avoids cell culture process and the use of manufactured scaffolds, has been proposed as a promising alternative to traditional tissue repair strategies within the field of craniofacial surgery [6,7,8]. This expedited tissue engineering strategy usefully employs biological stimuli to harness the intrinsic regenerative potential of endogenous tissues, such as muscle, fat, and bone marrow, to initiate the reparative processes in situ to improve or replace biological functions. Skeletal muscle biopsies from animals, after being genetically modified with

Objectives

Methods

Results