Evaluation of function and recovery of adipose-derived stem cells after exposure to paclitaxel

Cytotherapy. 2017 Feb;19(2):211-221. doi: 10.1016/j.jcyt.2016.10.010. Epub 2016 Nov 22.

Abstract

Background aims: Adipose-derived stem cells (ASCs) are considered to play a positive role in wound healing as evidenced by their increasing use in breast reconstructive procedures. After chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. In the present study, the functional capabilities and recovery of ASCs after exposure to chemotherapeutic agent paclitaxel (PTX) using in vitro and ex vivo models were demonstrated.

Methods: Human ASCs were isolated from periumbilical fat tissue and treated with PTX at various concentrations. Adult Sprague-Dawley rats were given intravenous injections with PTX. Two and four weeks after the initial PTX treatment, ASCs were isolated from rat adipose tissue. Proliferation, cell viability, apoptosis and cell migration rates were measured by growth curves, MTT assays, flow cytometry and scratch assays. ASCs were cultured in derivative-specific differentiation media with or without PTX for 3 weeks. Adipogenic, osteogenic and endothelial differentiation levels were measured by quantitative reverse transcriptase polymerase chain reaction and histological staining.

Results: PTX induced apoptosis, decreased the proliferation and cell migration rates of ASCs and inhibited ASCs multipotent differentiation in both in vitro human ASC populations and ex vivo rat ASC populations with PTX treatment. Furthermore, after cessation of PTX, ASCs exhibited recovery potential of differentiation capacity in both in vitro and animal studies.

Conclusions: Our results provide insight into poor soft tissue wound healing and promote further understanding of the potential capability of ASCs to serve as a cell source for fat grafting and reconstruction in cancer patients undergoing chemotherapy treatment.

Keywords: adipose-derived stem cells; breast cancer; paclitaxel; wound healing.

MeSH terms

  • Abdominal Fat / cytology
  • Abdominal Fat / drug effects
  • Adipose Tissue / cytology*
  • Adipose Tissue / drug effects
  • Adipose Tissue / pathology
  • Adult
  • Adult Stem Cells / drug effects*
  • Adult Stem Cells / physiology*
  • Animals
  • Apoptosis / drug effects
  • Breast Neoplasms / pathology
  • Breast Neoplasms / rehabilitation
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Female
  • Humans
  • Male
  • Osteogenesis / drug effects
  • Osteogenesis / physiology
  • Paclitaxel / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Wound Healing / drug effects

Substances

  • Paclitaxel