Gene-based approaches for the repair of articular cartilage.

Abstract:

:Gene transfer technology has opened novel treatment avenues toward the treatment of damaged musculoskeletal tissues, and may be particularly beneficial to articular cartilage. There is no natural repair mechanism to heal damaged or diseased cartilage. Existing pharmacologic, surgical and cell based treatments may offer temporary relief but are incapable of restoring damaged cartilage to its normal phenotype. Gene transfer provides the capability to achieve sustained, localized presentation of bioactive proteins or gene products to sites of tissue damage. A variety of cDNAs have been cloned which may be used to stimulate biological processes that could improve cartilage healing by (1) inducing mitosis and the synthesis and deposition of cartilage extracellular matrix components by chondrocytes, (2) induction of chondrogenesis by mesenchymal progenitor cells, or (3) inhibiting cellular responses to inflammatory stimuli. The challenge is to adapt this technology into a useful clinical treatment modality. Using different marker genes, the principle of gene delivery to synovium, chondrocytes and mesenchymal progenitor cells has been convincingly demonstrated. Following this, research efforts have begun to move to functional studies. This involves the identification of appropriate gene or gene combinations, incorporation of these cDNAs into appropriate vectors and delivery to specific target cells within the proper biological context to achieve a meaningful therapeutic response. Methods currently being explored range from those as simple as direct delivery of a vector to a cartilage defect, to synthesis of cartilaginous implants through gene-enhanced tissue engineering. Data from recent efficacy studies provide optimism that gene delivery can be harnessed to guide biological processes toward both accelerated and improved articular cartilage repair.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Trippel SB,Ghivizzani SC,Nixon AJ

doi

10.1038/sj.gt.3302201

keywords:

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

351-9

issue

4

eissn

0969-7128

issn

1476-5462

pii

3302201

journal_volume

11

pub_type

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