Fibrogenic and angiogenic commitments of human induced pluripotent stem cells derived mesenchymal stem cells in connective tissue growth factor-delivering scaffold in an immune-deficient mice model

J Biomed Mater Res B Appl Biomater. 2018 Aug;106(6):2266-2274. doi: 10.1002/jbm.b.34030. Epub 2017 Oct 31.

Abstract

Compared to terminal differentiated cells, stem cells play important roles in the maintenance and regeneration, and thus have been intensively researched as the most promising cell based therapy. In order to maximize the effectiveness of stem cell based therapies, it is essential to understand the environmental (niche) signals that regulate stem cell behavior. Recent findings suggest that fibroblasts have a mesenchymal origin and that mesenchymal stem cells (MSCs) demonstrate proangiogenic function, where both fibrogenic and angiogenic activities are associated with connective tissue growth factor (CTGF), a matricellular protein that serves as an essential mediator of skeletogenesis in development and vascular remodeling. Here, for the first time, we demonstrate that upon local delivery of CTGF from a three dimensional (3D) nanocomposite scaffold, human induced pluripotent stem cells derived MSCs can be directed to differentiate toward fibroblasts in a 3D nanocomposite scaffold in female nonobese diabetic CB-17/Icr-severe combined immunodeficient mice. The stem cell-scaffold constructs present not only intriguingly strong fibroblastic commitments but also angiogenic induction in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2266-2274, 2018.

Keywords: 3D scaffold; SCID mice; fibroblasts; stem cells; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Immobilized* / cytology
  • Cells, Immobilized* / metabolism
  • Cells, Immobilized* / transplantation
  • Connective Tissue Growth Factor* / chemistry
  • Connective Tissue Growth Factor* / pharmacology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Heterografts
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Nanocomposites / chemistry*
  • Tissue Scaffolds / chemistry*

Substances

  • CCN2 protein, human
  • Connective Tissue Growth Factor