Serum C-peptide level correlates with the course of muscle tissue healing in the rabbit model of critical limb ischemia

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019 Jun;163(2):132-140. doi: 10.5507/bp.2018.048. Epub 2018 Sep 7.

Abstract

Aim: The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI).

Methods: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood.

Results: Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing.

Conclusion: Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.

Keywords: C-peptide; critical limb ischemia; cytokines; mesenchymal stem cells; miR-126; tissue healing.

MeSH terms

  • Adult
  • Animals
  • C-Peptide / blood*
  • Cicatrix / pathology
  • Culture Media, Conditioned / pharmacology
  • Cytokines / blood*
  • Diabetes Mellitus, Experimental / blood*
  • Diabetic Foot
  • Disease Models, Animal
  • Fibrosis
  • Granulation Tissue / pathology
  • Hindlimb
  • Humans
  • In Situ Hybridization
  • Insulin / blood*
  • Ischemia / blood*
  • Male
  • Mesenchymal Stem Cells*
  • MicroRNAs / metabolism
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology*
  • Necrosis
  • Neovascularization, Physiologic / drug effects
  • Rabbits
  • Wound Healing / drug effects
  • Wound Healing / physiology*

Substances

  • C-Peptide
  • Culture Media, Conditioned
  • Cytokines
  • Insulin
  • MicroRNAs