4.7 Article

Cre/LoxP Genetic Recombination Sustains Cartilage Anabolic Factor Expression in Hyaluronan Encapsulated MSCs Alleviates Intervertebral Disc Degeneration

期刊

BIOMEDICINES
卷 10, 期 3, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines10030555

关键词

runx1 transcription factor; baculoviral vector; gene therapy; Cre/LoxP gene editing; disc degeneration

资金

  1. Minister of Science and Technology, Taiwan [MOST 109-2314-B-039-018-MY3, MOST 108-2622-E-039-002-CC1, MOST 108-2221-E-039-006-MY3]
  2. China Medical University [CMU109-MF-82]
  3. China Medical University Hospital [DMR-110-111, DMR-110-224, DMR-111-114]

向作者/读者索取更多资源

This study demonstrates the sustained expression of the cartilage-anabolic factor runx1 in MSCs, which are encapsulated in hyaluronan hydrogel and transplanted through micro-injection. The study shows that the runx1 gene expression has good biosafety characteristics and maintains superior hydration content in the intervertebral disc.
(1) Background: Inexplicable low back and neck pain frequently results from spinal disc degeneration with an imbalanced intervertebral disc (IVD) cell homeostasis. We hypothesize that introducing MSC expressing a sustained cartilage-anabolic factor in the IVD may stimulate the mucoid materials secreted from the WD cells, promote the MSC's chondrogenesis and maintain the hydration content providing mechanical strength to decelerate the disc degeneration progression; (2) Methods: This study expressed a cartilage-anabolic factor runx1 by a baculoviral vector (BV) transduced MSCs through a Cre/LoxP gene editing and recombination system for sustained recombinant runx1 transcription factor production. The Cre/LoxP BV modified MSCs were encapsulated by hyaluronan hydrogel, due to its' vital composition in ECM of a healthy disc and transplanted to a punctured coccygeal disc in rats through micro-injection, followed by X-ray radiography and histological analysis at the 4- and 12-weeks post-transplantation; (3) Results: Data reveals the Cre/LoxP BV system-mediated long-termed runx1 gene expression, possessing good biosafety characteristics in the in vitro cell transduction and in vivo MSCs transplantation, and maintained superior hydration content in the disc than that of mock transduced MSCs; (4) Conclusions: This proof-of-concept study fulfills the need of implanting therapeutic cells accompanied with microinjection in the disc, such as a discography and paves a road to manufacture composite hyaluronan, such as peptide modified hyaluronan as an MSC carrier for IVD regeneration in the future study.

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