Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors
Year: 2020
Type: article
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.
Source: Advanced Functional Materials
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, American Federation for Aging Research, Georgia Institute of Technology, National Research Foundation, Ministry of Science, ICT and Future Planning, National Research Foundation of Korea, National Institutes of Health, Parker H. Petit Institute for Bioengineering and Bioscience, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Electrical, Communications and Cyber Systems
Awards: G3326628579, Replicating heterochronic parabiosis on a 3D microfluidic chip to study systematic regulation of muscle stem cell, G3824688650, Implantable biofunctional hydrogel for muscle stem cell transplantation, G4424653204, G5032822916, NNCI: Southeastern Nanotechnology Infrastructure Corridor (SENIC), G5927359219, G6021866001, G618872819, G790860305, Probing the functional heterogeneity of high-density lipoprotein using physiological biomimicry, Advanced Delivery of Microglial Kv1.3 Channel Blocker for Attenuation of Neuroinflammation of Alzheimer's Disease, Replicating heterochronic parabiosis on a chip for testing anti-geronic factors, Engineered Heterochronic Parabiosis on 3D Microphysiological Systems
OpenAlex ID: W3080351408