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 language | English |
|---|---|
| Pages (from-to) | 233-243 |
| Number of pages | 11 |
| Journal | Tissue Engineering - Part A |
| Volume | 22 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - 2016 Feb 1 |
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ASJC Scopus subject areas
- Bioengineering
- Biochemistry
- Biomedical Engineering
- Biomaterials
Cite this
Inhibition of Rho-Associated Protein Kinase Increases the Angiogenic Potential of Mesenchymal Stem Cell Aggregates via Paracrine Effects. / Hong, Soyoung; Lee, Jae Yeon; Hwang, Changmo; Shin, Jennifer H.; Park, Yongdoo.
In: Tissue Engineering - Part A, Vol. 22, No. 3-4, 01.02.2016, p. 233-243.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Inhibition of Rho-Associated Protein Kinase Increases the Angiogenic Potential of Mesenchymal Stem Cell Aggregates via Paracrine Effects
AU - Hong, Soyoung
AU - Lee, Jae Yeon
AU - Hwang, Changmo
AU - Shin, Jennifer H.
AU - Park, Yongdoo
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84959042757&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2015.0289
DO - 10.1089/ten.tea.2015.0289
M3 - Article
C2 - 26592750
AN - SCOPUS:84959042757
VL - 22
SP - 233
EP - 243
JO - Tissue Engineering - Part A.
JF - Tissue Engineering - Part A.
SN - 1937-3341
IS - 3-4
ER -