Engineered Healing of Avascular Meniscus Tears by Stem Cell Recruitment

Sci Rep. 2018 May 25;8(1):8150. doi: 10.1038/s41598-018-26545-8.

Abstract

Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone. Upon injury, the outer zone of the meniscus can be repaired and expected to functionally heal but tears in the inner avascular region are unlikely to heal. To date, no regenerative therapy has been proven successful for consistently promoting healing in inner-zone meniscus tears. Here, we show that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) can induce seamless healing of avascular meniscus tears by inducing recruitment and step-wise differentiation of synovial mesenchymal stem/progenitor cells (syMSCs). A short-term release of CTGF, a selected chemotactic and profibrogenic cue, successfully recruited syMSCs into the incision site and formed an integrated fibrous matrix. Sustain-released TGFβ3 then led to a remodeling of the intermediate fibrous matrix into fibrocartilaginous matrix, fully integrating incised meniscal tissues with improved functional properties. Our data may represent a novel clinically relevant strategy to improve healing of avascular meniscus tears by recruiting endogenous stem/progenitor cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cattle
  • Connective Tissue Growth Factor / pharmacology
  • Meniscus / blood supply
  • Meniscus / drug effects
  • Meniscus / injuries*
  • Meniscus / physiopathology*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Tissue Engineering*
  • Transforming Growth Factor beta3 / pharmacology
  • Wound Healing* / drug effects

Substances

  • Transforming Growth Factor beta3
  • Connective Tissue Growth Factor