Microcurrent and adipose-derived stem cells modulate genes expression involved in the structural recovery of transected tendon of rats

FASEB J. 2020 Aug;34(8):10011-10026. doi: 10.1096/fj.201902942RR. Epub 2020 Jun 19.

Abstract

Tendon injuries are common and have a high incidence of re-rupture that can cause loss of functionality. Therapies with adipose-derived stem cells (ASC) and the microcurrent (low-intensity electrical stimulation) application present promising effects on the tissue repair. We analyzed the expression of genes and the participation of some molecules potentially involved in the structural recovery of the Achilles tendon of rats, in response to the application of both therapies, isolated and combined. The tendons were distributed in five groups: normal (N), transected (T), transected and ASC (C) or microcurrent (M) or with ASC, and microcurrent (MC). Microcurrent therapy was beneficial for tendon repair, as it was observed a statistically significant increase in the organization of the collagen fibers, with involvement of the TNC, CTGF, FN, FMDO, and COL3A1 genes as well as PCNA, IL-10, and TNF-α. ASC therapy significantly increased the TNC and FMDO genes expression with no changes in the molecular organization of collagen. With the association of therapies, a significant greater collagen fibers organization was observed with involvement of the FMOD gene. The therapies did not affect the expression of COL1A1, SMAD2, SMAD3, MKX, and EGR1 genes, nor did they influence the amount of collagen I and III, caspase-3, tenomodulin (Tnmd), and hydroxyproline. In conclusion, the application of the microcurrent isolated or associated with ASC increased the organization of the collagen fibers, which can result in a greater biomechanical resistance in relation to the tendons treated only with ASC. Future studies will be needed to demonstrate the biological effects of these therapies on the functional recovery of injured tendons.

Keywords: CTGF; cell therapy; collagen; electrical stimulation; tendon repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis*
  • Cell Differentiation
  • Cell Movement
  • Electric Stimulation / methods*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Rats
  • Rats, Wistar
  • Regeneration
  • Stem Cell Transplantation / methods*
  • Tendon Injuries / genetics
  • Tendon Injuries / metabolism
  • Tendon Injuries / pathology
  • Tendon Injuries / therapy*
  • Wound Healing*

Substances

  • Biomarkers