한빛사논문
Yunki Leea, Jeongmoon J. Choib,c, Song Ih Ahna,c, Nan Hee Leeb,c, Woojin M. Hana,c, Mahir Mohiuddinb,c,d, Eun Jung Shinb,c, Levi Wooda,c,d, Ki Dong Parke, YongTae Kima,c,d,f,* and Young C. Jangb,c,d,*
aGeorge W. Woodru School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
bSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
cParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
dWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
eDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea
fInstitute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332, USA
Y.L., J.J.C., and S.I.A. contributed equally to this work.
*To whom correspondence should be addressed.
Abstract
Exposure of a young systemic milieu reveals remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been reported, the exact underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the experimental challenges of using in vivo parabiosis. An in vitro parabiosis system is reported here that integrates young‐ and old‐muscle stem cell vascular niche on a 3D microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This 3D micro‐physiological system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. Using engineered parabiosis system, it is demonstrated that vascular endothelial growth factor signaling from endothelial cells and myotubes synergistically contributes to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on‐chip system, both blood transfusion and parabiosis can be mimicked and the time‐varying effects of antigeronic and progeronic factors can be monitored in a single organ or multiorgan systems. The microfluidic system can be utilized as a complementary in vitro microphysiological model to aid the complex in vivo parabiosis studies.
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