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한빛사논문
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Adv. Funct. Mater., Volume 28, Issue 41, October 10, 2018 | https://doi.org/10.1002/adfm.201802642
Remote Control of Intracellular Calcium Using Upconversion Nanotransducers Regulates Stem Cell Differentiation In Vivo
Heemin Kanga, Kunyu Zhanga, Qi Panb,c, Sien Linb,c,d, Dexter Siu Hong Wonga, Jinming Lia, Wayne Yuk-Wai Leeb,c, Boguang Yanga, Fengxuan Hane, Gang Lib,c,g, Bin Lie,f,* and Liming Biana,d,f,g,*
aDepartment of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077 Hong Kong, China
bDepartment of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
cStem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
dDepartment of Pharmacology, Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China
eDepartment of Orthopaedic Surgery, The First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou, Jiangsu 215006, China
fChina Orthopaedic Regenerative Medicine Group (CORMed), Hangzhou, Zhejiang 310058, China
eThe CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518172, China
*To whom correspondence should be addressed.
aDepartment of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077 Hong Kong, China
bDepartment of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
cStem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
dDepartment of Pharmacology, Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China
eDepartment of Orthopaedic Surgery, The First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou, Jiangsu 215006, China
fChina Orthopaedic Regenerative Medicine Group (CORMed), Hangzhou, Zhejiang 310058, China
eThe CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518172, China
*To whom correspondence should be addressed.
Abstract
Remote control of stem cell differentiation in vivo by stimuli-responsive nanomaterials with the use of tissue-penetrative stimuli is an appealing strategy for versatile regulation in stem cell therapy. In this study, an upconversion nanotransducer (UCNT)-based nanocomplex with photolabile caging of chondro-inductive kartogenin (KGN) and/or either calcium chelator or calcium supplier (caged calcium), and subsequent coupling of integrin-binding ligand via cyclodextrin-adamantine supramolecular complexation is utilized. Near-infrared (NIR)-to-ultraviolet light conversion by UCNT nanocomplex triggered intracellular photo-uncaging and release of cargo molecules, thereby allowing direct regulation of real-time intracellular calcium levels. While intracellular KGN delivery led to the differentiation of human mesenchymal stem cells (hMSCs) into hypertrophic chondrocytes, NIR-regulated intracellular calcium decrease and KGN delivery induced their differentiation into chondrocytes by inhibiting hypertrophy. Conversely, intracellular calcium increase and KGN delivery promoted the differentiation of hMSCs into osteoblasts via endochondral pathway. To the best of knowledge, this is the first demonstration of utilizing NIR-controllable nanomaterials for regulating stem cell differentiation by controlling intracellular calcium, both in vitro and in vivo. This versatile control can facilitate the translation of stem cells to remotely controlled treatment of diseases in composite tissues involving various cell types.
논문정보
- Research article
- 2018년 10월 (BRIC 등록일 2018-11-02)
- 국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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