Stem cells as vehicles for orthopedic gene therapy

Abstract

Adult stem cells reside in adult tissues and serve as the source for their specialized cells. In response to specific factors and signals, adult stem cells can differentiate and give rise to functional tissue specialized cells. Adult mesenchymal stem cells (MSCs) have the potential to differentiate into various mesenchymal lineages such as muscle, bone, cartilage, fat, tendon and ligaments. Adult MSCs can be relatively easily isolated from different tissues such as bone marrow, fat and muscle. Adult MSCs are also easy to manipulate and expand in vitro. It is these properties of adult MSCs that have made them the focus of cellmediated gene therapy for skeletal tissue regeneration. Adult MSCs engineered to express various factors not only deliver them in vivo, but also respond to these factors and differentiate into skeletal specialized cells. This allows them to actively participate in the tissue regeneration process. In this review, we examine the recent achievements and developments in stem-cell-based gene therapy approaches and their applications to bone, cartilage, tendon and ligament tissues that are the current focus of orthopedic medicine.

Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells

“…5 Because MSCs can be easily expanded in vitro and retain an extensive multipotent capacity for differentiation, there has been much interest in their clinical potential for tissue repair and gene therapy. 6 Another important biological feature of MSCs has recently been identified: after systemic injection, MSCs can selectively migrate via the blood stream to solid tumors, where they proliferate and become stromal cells. [7][8][9] These features suggest that MSCs could be used as a cellular vehicle of gene delivery to tumor sites.…”

Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty

“…MSCs have inherent osteogenic capacity and can respond to BMP that they have been engineered to secrete. 43,44 This enables them to actively contribute to periodontal tissue regeneration. The approach used here for the advBMP-2 group provided a larger quantity of osteoprogenitor cells into which MSCs can differentiate, to support osteogenesis and cementogenesis within the connective tissue between bone and tooth.…”

“…10 Adult bone marrow mesenchymal stem cells (MSCs) can be engineered to express an assortment of factors in vivo; moreover, they have been demonstrated to respond to these factors and differentiate into skeletal specialized cells. 11 This allows them to actively contribute to periodontal tissue regeneration. Relative to the fibroblast approach, more prolonged and efficient delivery of BMP-2 can be accomplished in vivo when using viral vectors to introduce the BMP-2 gene into MSCs.…”

Augmented anti-tumor therapy through natural targetability of macrophages genetically engineered by NK4 plasmid DNA

“…To achieve this genetic engineering of cells, virus carriers have been mainly used because of the high efficiency of gene transfection. [2][3][4][5][6][7][8] However, there are several problems to be resolved for the clinical applications, such as the antigenicity and toxicity of virus itself or the possibility of disease transfection. Therefore, efficient technology and methodology of gene transfection without virus vectors are highly expected.…”