An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury

Biomolecules. 2020 Sep 9;10(9):1301. doi: 10.3390/biom10091301.

Abstract

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, cluster of differentiation (CD) immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and βIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI; furthermore, it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI.

Keywords: angiogenic activity; mesenchymal stem/stromal cell; neurotrophic activity; regenerative medicine; spinal cord injury; translational research.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Collagen
  • Culture Media, Conditioned
  • Dogs
  • Drug Combinations
  • Endothelial Cells / physiology
  • Humans
  • In Vitro Techniques
  • Laminin
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Neovascularization, Physiologic
  • Neuronal Outgrowth / physiology
  • Neurons / physiology
  • Paracrine Communication
  • Proteoglycans
  • Spinal Cord Injuries / therapy*
  • Tubulin / metabolism

Substances

  • Culture Media, Conditioned
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • Tubulin
  • matrigel
  • Collagen