A Sendai virus-based expression system directs efficient induction of chondrocytes by transcription factor-mediated reprogramming.
Chondrocytes
/ metabolism
Animals
Sendai virus
/ genetics
Genetic Vectors
/ genetics
Mice
Kruppel-Like Factor 4
/ metabolism
Cellular Reprogramming
/ genetics
SOX9 Transcription Factor
/ metabolism
Chondrogenesis
/ genetics
Proto-Oncogene Proteins c-myc
/ metabolism
Kruppel-Like Transcription Factors
/ genetics
Humans
Transduction, Genetic
Osteoarthritis
/ metabolism
Cell Differentiation
Transcription Factors
/ genetics
Chondrocyte
Direct reprogramming
Osteoarthritis
Sendai virus vector
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 10 2024
29 10 2024
Historique:
received:
12
06
2024
accepted:
23
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Cartilage rarely heals spontaneously once damaged. Osteoarthritis (OA) is the most common degenerative joint disease among the elderly; however, effective treatment for OA is currently lacking. Autologous chondrocyte implantation (ACI), an innovative regenerative technology involving the implantation of healthy chondrocytes, may restore damaged lesions. Chondrocytes for ACI may potentially be induced from differentiated somatic cells using retrovirus (RV)-mediated transduction of three reprogramming factors (SOX9, KLF4, and c-MYC). However, the efficiency of the current induction system needs to be improved and the safety issues arising from the genomic integration of the vector DNA have to be addressed. To solve these problems, we used an RNA vector, termed the replication-defective and persistent Sendai virus vector (SeVdp), to express reprogramming factors for chondrocyte induction. Our results showed that the SeVdp-based vector induced chondrocytes more efficiently than the RV vector, probably because of robust and rapid expression of the transgenes, without any apparent integration of the SeVdp vector. The induced chondrocytes formed cartilage-like tissues when injected subcutaneously into mice. Thus, the SeVdp-based system for inducing chondrocytes may act as a foundation for developing safer and more effective treatments for damaged cartilage.
Identifiants
pubmed: 39472618
doi: 10.1038/s41598-024-77508-1
pii: 10.1038/s41598-024-77508-1
doi:
Substances chimiques
Kruppel-Like Factor 4
0
SOX9 Transcription Factor
0
Klf4 protein, mouse
0
Proto-Oncogene Proteins c-myc
0
Kruppel-Like Transcription Factors
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26004Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP19H03203
Organisme : Japan Society for the Promotion of Science
ID : JP17H04036
Organisme : Japan Society for the Promotion of Science
ID : JP19K07343
Organisme : Japan Agency for Medical Research and Development
ID : JP22ym0126803
Informations de copyright
© 2024. The Author(s).
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