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Marrow Transplantation and Targeted Gene Therapy to the Skeleton.

Lian, Jane B. PhD; Stein, Gary S. PhD; Stein, Janet L. PhD; van Wijnen, André J. PhD

Clinical Orthopaedics & Related Research: October 2000 - Volume 379 - Issue - pp S146-S155
Section III Bone

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.

From the Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA.

The studies were supported by grants from the National Institutes of Health (DE12528 and AR39588). It's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Reprint requests to Jane B. Lian, PhD, Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.

© 2000 Lippincott Williams & Wilkins, Inc.