Gene therapy for chondral and osteochondral regeneration: is the future now?

Abstract

Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies. Genes delivered encoded mainly for growth factors, followed by transcription factors, anti-inflammatory cytokines and, less frequently, by cell signalling proteins, matrix proteins and receptors. Direct injection of the expression vector was used less than indirect injection of cells, with or without scaffolds, transduced with genes of interest and then implanted into the lesion site. Clinical trials (phases I, II or III) on safety, biological activity, efficacy, toxicity or bio-distribution employed adenovirus viral vectors to deliver growth factors or anti-inflammatory cytokines, for the treatment of osteoarthritis or degenerative arthritis, and tumour necrosis factor receptor or interferon for the treatment of inflammatory arthritis.

Keywords: Cartilage repair; Expression vectors; Gene therapy procedures; Osteoarthritis; Regenerative medicine.

Fig. 1

Diagram of the reference search strategy and selection

Fig. 2

Schematic drawing of classes of expression vector

Fig. 3

Barcharts of the number of preclinical in vitro, ex vivo and in vivo studies that employed non-viral and viral vectors

Fig. 4

Barcharts of the number of groups of genes evaluated in preclinical, in vitro, ex vivo and in vivo studies

Fig. 5

Barcharts of the number of procedures (direct and indirect) to bring genes into cartilaginous defects according to the modality of administration of the selected vector

Fig. 6

Schematic drawing of different modalities of administration of the expression vector

Fig. 7

Barcharts of the number of indirect procedure studies that employed different techniques for gene therapy