Therapeutic Effect of a Xeno-Free Three-Dimensional Stem Cell Mass in a Hind Limb Ischemia Model

Tissue Eng Part A. 2019 Mar;25(5-6):314-332. doi: 10.1089/ten.TEA.2018.0089. Epub 2018 Dec 12.

Abstract

We describe an innovative method of culturing a three-dimensional cell mass (3DCM) of human adipose-derived stem cells (hASCs) in the xeno-free (XF) condition for the treatment of severe ischemic diseases. The majority of the mice injected with XF-3DCMs exhibited limb salvaging and displayed similar blood perfusion compared to normal limbs. In vivo tumorigenicity and toxicity analysis showed that XF-3DCMs did not transform into tumor cells and induce toxicity, respectively. Our results strongly suggest that XF-3DCMs can be effectively used for therapeutic applications and eliminate immunological reaction of animal-derived material contamination.

Keywords: cell therapy; human adipose-derived stem cells; three-dimensional stem cell mass; toxicity test; tumorigenicity test; xeno-free media.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Carcinogenesis / drug effects
  • Carcinogenesis / pathology
  • Cell Survival / drug effects
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibrosis
  • Gene Expression Regulation / drug effects
  • Hindlimb / blood supply*
  • Hindlimb / pathology*
  • Humans
  • Ischemia / therapy*
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Muscles / drug effects
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Stem Cells / drug effects

Substances

  • Fibroblast Growth Factor 2