Regenerating cartilages by engineered ASCs: Prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure

Chia Hsin Lu, Tsung Szu Yeh, Chia Lin Yeh, Yu-Hua Dean Fang, Li Yu Sung, Shih Yeh Lin, Tzu Chen Yen, Yu Han Chang, Yu Chen Hu

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Adipose-derived stem cells (ASCs) hold promise for cartilage regeneration but their chondrogenesis potential is inferior. Here, we used a baculovirus (BV) system that exploited FLPo/Frt-mediated transgene recombination and episomal minicircle formation to genetically engineer rabbit ASCs (rASCs). The BV system conferred prolonged and robust TGF-β3/BMP-6 expression in rASCs cultured in porous scaffolds, which critically augmented rASCs chondrogenesis and suppressed osteogenesis/hypertrophy, leading to the formation of cartilaginous constructs with improved maturity and mechanical properties in 2-week culture. Twelve weeks after implantation into full-thickness articular cartilage defects in rabbits, these engineered constructs regenerated neocartilages that resembled native hyaline cartilages in cell morphology, matrix composition and mechanical properties. The neocartilages also displayed cartilage-specific zonal structures without signs of hypertrophy and degeneration, and eventually integrated with host cartilages. In contrast, rASCs that transiently expressed TGF-β3/BMP-6 underwent osteogenesis/hypertrophy and resulted in the formation of inferior cartilaginous constructs, which after implantation regenerated fibrocartilages. These data underscored the crucial role of TGF-β3/BMP-6 expression level and duration in rASCs in the cell differentiation, constructs properties and in vivo repair. The BV-engineered rASCs that persistently express TGF-β3/BMP-6 improved the chondrogenesis, in vitro cartilaginous constructs production and in vivo hyaline cartilage regeneration, thus representing a remarkable advance in cartilage engineering.

Original languageEnglish
Pages (from-to)186-195
Number of pages10
JournalMolecular Therapy
Volume22
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Bone Morphogenetic Protein 6
Articular Cartilage
Cartilage
Stem Cells
Rabbits
Chondrogenesis
Baculoviridae
Hypertrophy
Hyaline Cartilage
Osteogenesis
Regeneration
Fibrocartilage
Transgenes
Genetic Recombination
Cell Differentiation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Lu, Chia Hsin ; Yeh, Tsung Szu ; Yeh, Chia Lin ; Fang, Yu-Hua Dean ; Sung, Li Yu ; Lin, Shih Yeh ; Yen, Tzu Chen ; Chang, Yu Han ; Hu, Yu Chen. / Regenerating cartilages by engineered ASCs : Prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure. In: Molecular Therapy. 2014 ; Vol. 22, No. 1. pp. 186-195.
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Regenerating cartilages by engineered ASCs : Prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure. / Lu, Chia Hsin; Yeh, Tsung Szu; Yeh, Chia Lin; Fang, Yu-Hua Dean; Sung, Li Yu; Lin, Shih Yeh; Yen, Tzu Chen; Chang, Yu Han; Hu, Yu Chen.

In: Molecular Therapy, Vol. 22, No. 1, 01.01.2014, p. 186-195.

Research output: Contribution to journalArticle

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