Title
Marrow transplantation and targeted gene therapy to the skeleton
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences;; Department of Cell Biology and Cancer Center
Date
10-20-2000
Document Type
Article
Medical Subject Headings
Animals; Bone Marrow Transplantation; Gene Expression; *Gene Therapy; Genes, Reporter; *Hematopoietic Stem Cell Transplantation; Osteocalcin; *Osteogenesis; Promoter Regions (Genetics); Transcription Factors
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Treatment of genetic or degenerative diseases severely affecting the entire skeleton may necessitate gene therapy involving transplantation of multipotential marrow cells. The ability of in vitro expanded adherent marrow cells enriched in pluripotent mesenchymal cell populations to remain competent to engraft, repopulate host tissues, and differentiate into bone and cartilage is advantageous for correction of skeletal-related diseases. However, to achieve phenotypic specificity and therapeutic or physiologic levels of proteins may require cell type specific expression of the gene. Tissue-specific promoter-controlled transgenes provide an efficacious approach to deliver therapeutic gene expression to repopulating chondrocytes and osteoblasts for treatment of cartilage and bone disorders or tumor metastasis to the skeleton. The bone-specific expression of a reporter gene controlled by the osteoblast-specific osteocalcin promoter after transplantation of a mixed population of marrow cells is shown. Tissue-restricted gene therapy potentially can be refined by use of a unique peptide targeting signal that directs the hematopoietic, chondrogenic, and osteogenic core binding factor/acute myelogenous leukemia transcription factors to subnuclear sites that support gene expression.
Rights and Permissions
Citation: Clin Orthop Relat Res. 2000 Oct;(379 Suppl):S146-55.