Inhibition of Rho-Associated Protein Kinase Increases the Angiogenic Potential of Mesenchymal Stem Cell Aggregates via Paracrine Effects

Soyoung Hong, Jae Yeon Lee, Changmo Hwang, Jennifer H. Shin, Yongdoo Park

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The aggregation of multiple cells, such as mesenchymal condensation, is an important biological process in skeletal muscle development, osteogenesis, and adipogenesis. Due to limited in vivo study model systems, a simple and effective in vitro three-dimensional (3D) aggregation system is required to study the mechanisms of multicellular aggregation and its applications. We first generated controlled mesenchymal stem cell (MSC) aggregates using a bioprinting technique to monitor their aggregation and sprouting. We induced the angiogenic potential of the MSCs through chemical inhibition of the Rho/Rho-associated protein kinase (ROCK) pathway, which led to hairy sprouting in the aggregates. The angiogenic potential of this 3D construct was then tested by subcutaneously implanting the Matrigel with 3D MSC aggregates in a rat. Treatment of 3D MSCs with the ROCK inhibitor, Y27632, increased their angiogenic activity in vivo. The gene expressions and histological staining indicated that angiogenesis and neovascularization were mainly regulated by the paracrine factors secreted from human 3D MSC constructs. Our results demonstrate the enhancement of the angiogenic potential of the MSC constructs through the secretion of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) by the inhibition of the Rho/ROCK pathway.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalTissue Engineering - Part A
Volume22
Issue number3-4
DOIs
Publication statusPublished - 2016 Feb 1

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

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