TY - JOUR
T1 - Tethering transforming growth factor β1 to soft hydrogels guides vascular smooth muscle commitment from human mesenchymal stem cells
AU - Ding, Yonghui
AU - Johnson, Richard
AU - Sharma, Sadhana
AU - Ding, Xiaoyun
AU - Bryant, Stephanie J.
AU - Tan, Wei
N1 - Funding Information:
The authors gratefully acknowledge funding by NIH (NHLBI 097246 to W. Tan). The authors also thank Professor Corey Neu (Department of Mechanical Engineering, CU-Boulder), Dr. Dragavon, and the BioFrontiers Advanced Light Microscopy for their excellent microscopy and imaging support.
Funding Information:
The authors gratefully acknowledge funding by NIH (NHLBI 097246 to W. Tan). The authors also thank Professor Corey Neu (Department of Mechanical Engineering, CU-Boulder), Dr. Dragavon, and the BioFrontiers Advanced Light Microscopy for their excellent microscopy and imaging support.
Publisher Copyright:
© 2020 Acta Materialia Inc.
PY - 2020/3/15
Y1 - 2020/3/15
N2 - Mesenchymal stem cells (MSCs) hold great promise for vascular smooth muscle regeneration. However, most studies have mainly relied on extended supplementation of sophisticated biochemical regimen to drive MSC differentiation towards vascular smooth muscle cells (vSMCs). Herein we demonstrate a concomitant method that exploits the advantages of biomimetic matrix stiffness and tethered transforming growth factor β1 (TGF-β1) to guide vSMC commitment from human MSCs. Our designed poly(ethylene glycol) hydrogels, presenting a biomimetic stiffness and tethered TGF-β1, provide an instructive environment to potently upregulate smooth muscle marker expression in vitro and in vivo. Importantly, it significantly enhances the functional contractility of vSMCs derived from MSCs within 3 days. Interestingly, compared to non-tethered one, tethered TGF-β1 enhanced the potency of vSMC commitment on hydrogels. We provide compelling evidence that combining stiffness and tethered TGF-β1 on poly(ethylene glycol) hydrogels can be a promising approach to drastically enhance maturation and function of vSMCs from stem cell differentiation in vitro and in vivo. Statement of Significance: A fast, reliable and safe regeneration of vascular smooth muscle cells (vSMCs) from stem cell differentiation is promising for vascular tissue engineering and regenerative medicine applications, but remains challenging. Herein, a photo-click hydrogel platform is devised to recapitulate the stiffness of vascular tissue and appropriate presentation of transforming growth factor β1 (TGF-β1) to guide vSMC commitment from mesenchymal stem cells (MSCs). We demonstrate that such concomitant method drastically enhanced regeneration of mature, functional vSMCs from MSCs in vitro and in vivo within only a 3-days span. This work is not only of fundamental scientific importance, revealing how physiochemical factors and the manner of their presentation direct stem cell differentiation, but also attacks the long-standing difficulty in regenerating highly functional vSMCs within a short period.
AB - Mesenchymal stem cells (MSCs) hold great promise for vascular smooth muscle regeneration. However, most studies have mainly relied on extended supplementation of sophisticated biochemical regimen to drive MSC differentiation towards vascular smooth muscle cells (vSMCs). Herein we demonstrate a concomitant method that exploits the advantages of biomimetic matrix stiffness and tethered transforming growth factor β1 (TGF-β1) to guide vSMC commitment from human MSCs. Our designed poly(ethylene glycol) hydrogels, presenting a biomimetic stiffness and tethered TGF-β1, provide an instructive environment to potently upregulate smooth muscle marker expression in vitro and in vivo. Importantly, it significantly enhances the functional contractility of vSMCs derived from MSCs within 3 days. Interestingly, compared to non-tethered one, tethered TGF-β1 enhanced the potency of vSMC commitment on hydrogels. We provide compelling evidence that combining stiffness and tethered TGF-β1 on poly(ethylene glycol) hydrogels can be a promising approach to drastically enhance maturation and function of vSMCs from stem cell differentiation in vitro and in vivo. Statement of Significance: A fast, reliable and safe regeneration of vascular smooth muscle cells (vSMCs) from stem cell differentiation is promising for vascular tissue engineering and regenerative medicine applications, but remains challenging. Herein, a photo-click hydrogel platform is devised to recapitulate the stiffness of vascular tissue and appropriate presentation of transforming growth factor β1 (TGF-β1) to guide vSMC commitment from mesenchymal stem cells (MSCs). We demonstrate that such concomitant method drastically enhanced regeneration of mature, functional vSMCs from MSCs in vitro and in vivo within only a 3-days span. This work is not only of fundamental scientific importance, revealing how physiochemical factors and the manner of their presentation direct stem cell differentiation, but also attacks the long-standing difficulty in regenerating highly functional vSMCs within a short period.
KW - Hydrogels
KW - Mesenchymal stem cells
KW - Smooth muscle cells
KW - Stiffness
KW - Transforming growth factor β1
UR - http://www.scopus.com/inward/record.url?scp=85079120833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079120833&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2020.01.034
DO - 10.1016/j.actbio.2020.01.034
M3 - Article
C2 - 31982589
AN - SCOPUS:85079120833
SN - 1742-7061
VL - 105
SP - 68
EP - 77
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -
