Low-level laser and adipose-derived stem cells altered remodelling genes expression and improved collagen reorganization during tendon repair

Cell Prolif. 2019 May;52(3):e12580. doi: 10.1111/cpr.12580. Epub 2019 Feb 7.

Abstract

Objectives: The cellular therapy using adipose-derived mesenchymal stem cells (ASCs) aims to improve tendon healing, considering that repaired tendons often result in a less resistant tissue. Our objective was to evaluate the effects of the ASCs combination with a low-level laser (LLL), an effective photobiostimulation for the healing processes.

Materials and methods: Rats calcaneal tendons were divided into five groups: normal (NT), transected (T), transected and ASCs (SC) or LLL (L), or with ASCs and LLL (SCL).

Results: All treated groups presented higher expression of Dcn and greater organization of collagen fibres. In comparison with T, LLL also up-regulated Gdf5 gene expression, ASCs up-regulated the expression of Tnmd, and the association of LLL and ASCs down-regulated the expression of Scx. No differences were observed for the expression of Il1b, Timp2, Tgfb1, Lox, Mmp2, Mmp8 and Mmp9, neither in the quantification of hydroxyproline, TNF-α, PCNA and in the protein level of Tnmd. A higher amount of IL-10 was detected in SC, L and SCL compared to T, and higher amount of collagen I and III was observed in SC compared to SCL.

Conclusions: Transplanted ASCs migrated to the transected region, and all treatments altered the remodelling genes expression. The LLL was the most effective in the collagen reorganization, followed by its combination with ASCs. Further investigations are needed to elucidate the molecular mechanisms involved in the LLL and ASCs combination during initial phases of tendon repair.

Keywords: GDF-5; cell therapy; decorin; healing; photobiostimulation; tenomodulin.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Collagen / metabolism*
  • Gene Expression / radiation effects
  • Growth Differentiation Factor 5 / genetics
  • Low-Level Light Therapy*
  • Male
  • Membrane Proteins / genetics
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / radiation effects*
  • Rats
  • Rats, Inbred Lew
  • Rats, Transgenic
  • Rats, Wistar
  • Tendon Injuries / genetics
  • Tendon Injuries / metabolism*
  • Tendon Injuries / therapy*
  • Wound Healing / genetics
  • Wound Healing / radiation effects

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • GDF5 protein, rat
  • Growth Differentiation Factor 5
  • Membrane Proteins
  • Scx protein, rat
  • Tnmd protein, rat
  • Collagen

Associated data

  • GENBANK/NM_017008
  • GENBANK/NM_001130508
  • GENBANK/NM_022290
  • GENBANK/NM_031512
  • GENBANK/NM_021578
  • GENBANK/NM_031054
  • GENBANK/NM_031055
  • GENBANK/NM_021989
  • GENBANK/NM_024129
  • GENBANK/NM_017061
  • GENBANK/XM_001066344