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.
| Original language | English |
|---|---|
| Article number | 1802642 |
| Journal | Advanced Functional Materials |
| Volume | 28 |
| Issue number | 41 |
| DOIs | |
| Publication status | Published - 2018 Oct 10 |
| Externally published | Yes |
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Keywords
- in vivo stem cell differentiation
- intracellular calcium regulation
- photocaging
- upconversion nanotransducers
ASJC Scopus subject areas
- Chemistry(all)
- Materials Science(all)
- Condensed Matter Physics
Cite this
Remote Control of Intracellular Calcium Using Upconversion Nanotransducers Regulates Stem Cell Differentiation In Vivo. / Kang, Heemin; Zhang, Kunyu; Pan, Qi; Lin, Sien; Wong, Dexter Siu Hong; Li, Jinming; Lee, Wayne Yuk Wai; Yang, Boguang; Han, Fengxuan; Li, Gang; Li, Bin; Bian, Liming.
In: Advanced Functional Materials, Vol. 28, No. 41, 1802642, 10.10.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Remote Control of Intracellular Calcium Using Upconversion Nanotransducers Regulates Stem Cell Differentiation In Vivo
AU - Kang, Heemin
AU - Zhang, Kunyu
AU - Pan, Qi
AU - Lin, Sien
AU - Wong, Dexter Siu Hong
AU - Li, Jinming
AU - Lee, Wayne Yuk Wai
AU - Yang, Boguang
AU - Han, Fengxuan
AU - Li, Gang
AU - Li, Bin
AU - Bian, Liming
PY - 2018/10/10
Y1 - 2018/10/10
N2 - 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.
AB - 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.
KW - in vivo stem cell differentiation
KW - intracellular calcium regulation
KW - photocaging
KW - upconversion nanotransducers
UR - http://www.scopus.com/inward/record.url?scp=85052819899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052819899&partnerID=8YFLogxK
U2 - 10.1002/adfm.201802642
DO - 10.1002/adfm.201802642
M3 - Article
AN - SCOPUS:85052819899
VL - 28
JO - Advanced Functional Materials
JF - Advanced Functional Materials
SN - 1616-301X
IS - 41
M1 - 1802642
ER -