Telomere Length as a Tool to Monitor Satellite Cell Amplification for Cell-Mediated Gene Therapy

Abstract

Cell-mediated gene therapy requires an in vitro amplification of modified cells prior to their injection into target tissue. Since the proliferative capacity of normal human cells is limited, we have tested a method to follow in vitro the proliferative potential of human satellite cells. Our results show that telomere length can be used to predict the proliferative potential of human satellite cells. In this short communication, the telomere shortening and the limited replicative potential are discussed in the context of the possible use of human satellite cells for gene transfer and why cell-mediated gene therapy has been less successful in humans than in mice.

Overview summary

Skeletal muscle is composed of multinucleated fibers formed by the fusion of mononucleated myogenic precursor cells. Late fetal and postnatal muscle growth as well as muscle regeneration occurs via the proliferation and fusion of satellite cells that are situated between the plasma membrane and the basal lamina of the muscle fibers. Satellite cells can be isolated in culture, amplified, and then reinjected into a host muscle where they will become incorporated into growing or regenerating muscle fibers. These cells have now become a key target for cell mediated gene therapy and myoblast transplantation both in the mouse and in man. Human somatic cells, however, have a limited life span, which means that during any amplification procedures prior to reinjection into a host tissue the proliferation should be carefully followed so that the cells do not become too close to senescence. In this study we show that telomere length can be used as a tool to monitor satellite cell amplification for gene therapy.