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Advances in experimental medicine and biology2023; 1402; 95-105; doi: 10.1007/978-3-031-25588-5_7

Gene Delivery to Chondrocytes.

Abstract: Delivering genes to chondrocytes offers new possibilities both clinically, for treating conditions that affect cartilage, and in the laboratory, for studying the biology of chondrocytes. Advances in gene therapy have created a number of different viral and non-viral vectors for this purpose. These vectors may be deployed in an ex vivo fashion, where chondrocytes are genetically modified outside the body, or by in vivo delivery where the vector is introduced directly into the body; in the case of articular and meniscal cartilage in vivo delivery is typically by intra-articular injection. Ex vivo delivery is favored in strategies for enhancing cartilage repair as these can be piggy-backed on existing cell-based technologies, such as autologous chondrocyte implantation, or used in conjunction with marrow-stimulating techniques such as microfracture. In vivo delivery to articular chondrocytes has proved more difficult, because the dense, anionic, extra-cellular matrix of cartilage limits access to the chondrocytes embedded within it. As Grodzinsky and colleagues have shown, the matrix imposes strict limits on the size and charge of particles able to diffuse through the entire depth of articular cartilage. Empirical observations suggest that the larger viral vectors, such as adenovirus (~100 nm), are unable to transduce chondrocytes in situ following intra-articular injection. However, adeno-associated virus (AAV; ~25 nm) is able to do so in horse joints. AAV is presently in clinical trials for arthritis gene therapy, and it will be interesting to see whether human chondrocytes are also transduced throughout the depth of cartilage by AAV following a single intra-articular injection. Viral vectors have been used to deliver genes to the intervertebral disk but there has been little research on gene transfer to chondrocytes in other cartilaginous tissues such as nasal, auricular or tracheal cartilage.
© 2023. The Author(s).
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Publication Date: 2023-04-14 PubMed ID: 37052849PubMed Central: 9274665DOI: 10.1007/978-3-031-25588-5_7Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores the possibilities of using gene delivery to treat cartilage-related conditions and to understand the biology of chondrocytes, cells that lie within the cartilage. Advances in gene therapy have made it possible to use different viral and non-viral vectors for gene delivery, either by modifying chondrocytes outside of the body (ex vivo) or by directly introducing them into the body (in vivo).

Gene Delivery Techniques

  • The research identifies two primary methods of gene delivery: ex vivo and in vivo. Ex vivo method involves genetic modification of chondrocytes outside the body, while in vivo involves direct gene introduction within the body, commonly achieved by intra-articular injection for articular and meniscal cartilage.
  • Ex vivo delivery is preferable when enhancing cartilage repair due to its ability to be combined with other cell-based technologies like autologous chondrocyte implantation or marrow-stimulating techniques such as microfracture.
  • In vivo delivery to articular chondrocytes, on the other hand, poses more challenges due to the dense, anionic, extra-cellular matrix of the cartilage which limits access to the embedded chondrocytes. This matrix sets strict conditions on the size and charge of particles that can diffuse through the entire cartilage depth.

Role of Viral Vectors

  • Viral vectors such as the adenovirus and adeno-associated virus (AAV) are employed in gene delivery. Adenovirus, due to its larger size, is unable to transduce chondrocytes following intra-articular injection. On the other hand, AAV, being smaller, has proven capable of achieving this in horse joints.
  • Presently, AAV is being used in clinical trials for arthritis gene therapy. The study aims to see if human chondrocytes would also respond similarly to AAV delivery following a singular intra-articular injection.
  • While viral vectors have been utilized in gene delivery to the intervertebral disk, the study notes a shortage of research on gene transfer to chondrocytes in other cartilaginous tissues like nasal, auricular or tracheal cartilage.

Cite This Article

APA
Nagelli CV, Evans CH, De la Vega RE. (2023). Gene Delivery to Chondrocytes. Adv Exp Med Biol, 1402, 95-105. https://doi.org/10.1007/978-3-031-25588-5_7

Publication

Advances in experimental medicine and biology
ISSN: 0065-2598
NlmUniqueID: 0121103
Country: United States
Language: English
Volume: 1402
Pages: 95-105

Researcher Affiliations

Nagelli, Christopher V
  • Musculoskeletal Gene Therapy Laboratory, Mayo Clinic, Rochester, MN, USA.
Evans, Christopher H
  • Musculoskeletal Gene Therapy Laboratory, Mayo Clinic, Rochester, MN, USA. Evans.christopher@mayo.edu.
De la Vega, Rodolfo E
  • Musculoskeletal Gene Therapy Laboratory, Mayo Clinic, Rochester, MN, USA.

MeSH Terms

  • Humans
  • Animals
  • Horses
  • Chondrocytes
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Cartilage, Articular
  • Injections, Intra-Articular

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Citations

This article has been cited 1 times.
  1. Roseti L, Cavallo C, Desando G, D'Alessandro M, Grigolo B. Forty Years of the Use of Cells for Cartilage Regeneration: The Research Side. Pharmaceutics 2024 Dec 22;16(12).
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