Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel

Seong Mi Choi; Kyoung Mi Lee; Seung Bae Ryu; Yoo Jung Park; Yeok Gu Hwang; Dawoon Baek; Yoorim Choi; Kwang Hwan Park; Ki Dong Park; Jin Woo Lee

doi:10.1038/s41419-018-0914-1

Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel

Seong Mi Choi, Kyoung Mi Lee, Seung Bae Ryu, Yoo Jung Park, Yeok Gu Hwang, Dawoon Baek, Yoorim Choi, Kwang Hwan Park, Ki Dong Park, Jin Woo Lee

Department of Orthopaedic Surgery

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

To investigate the functional effects of resveratrol (RSV) on mesenchymal stem cells (MSCs), we treated MSCs with RSV continuously during ex vivo expansion. MSCs were continuously treated with RSV from passage (P) 0 to P5. A proliferative capacity of RSV-treated MSCs was higher than that of non-treated MSCs and similar with P1-MSCs. Continuous treatment of RSV on MSCs increased the stemness and inhibited the senescence. During chondrogenic differentiation in vitro, RSV-treated MSCs had higher differentiation potential and reduced hypertrophic maturation, which are limitations for hyaline cartilage formation. The histological analysis of micromass demonstrated increased chondrogenic differentiation potential. We further explored the therapeutic effectiveness of this method in a rabbit osteochondral defect model. A rabbit osteochondral defect model was established to investigate the hyaline cartilage regeneration potential of RSV-treated MSCs. Moreover, the cartilage regeneration potential of RSV-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in RSV-treated MSCs compared with untreated MSCs. Sustained treatment of RSV on MSCs during ex vivo expansion resulted in the maintenance of stemness and enhanced chondrogenic differentiation potential. Consequentially, highly efficient MSCs promoted superior hyaline cartilage regeneration in vivo. This novel treatment method provides a basis for cell-based tissue engineering.

Original language	English
Article number	866
Journal	Cell Death and Disease
Volume	9
Issue number	9
DOIs	https://doi.org/10.1038/s41419-018-0914-1
Publication status	Published - 2018 Sept 1

Bibliographical note

Funding Information:
This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. NRF-2016R1D1A1B03933182), and from the NRF grant funded by the Korea government (MSIP) (NRF-2018R1A2B2004529).

Publisher Copyright:
© 2018, The Author(s).

All Science Journal Classification (ASJC) codes

Immunology
Cellular and Molecular Neuroscience
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41419-018-0914-1

Cite this

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title = "Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel",

abstract = "To investigate the functional effects of resveratrol (RSV) on mesenchymal stem cells (MSCs), we treated MSCs with RSV continuously during ex vivo expansion. MSCs were continuously treated with RSV from passage (P) 0 to P5. A proliferative capacity of RSV-treated MSCs was higher than that of non-treated MSCs and similar with P1-MSCs. Continuous treatment of RSV on MSCs increased the stemness and inhibited the senescence. During chondrogenic differentiation in vitro, RSV-treated MSCs had higher differentiation potential and reduced hypertrophic maturation, which are limitations for hyaline cartilage formation. The histological analysis of micromass demonstrated increased chondrogenic differentiation potential. We further explored the therapeutic effectiveness of this method in a rabbit osteochondral defect model. A rabbit osteochondral defect model was established to investigate the hyaline cartilage regeneration potential of RSV-treated MSCs. Moreover, the cartilage regeneration potential of RSV-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in RSV-treated MSCs compared with untreated MSCs. Sustained treatment of RSV on MSCs during ex vivo expansion resulted in the maintenance of stemness and enhanced chondrogenic differentiation potential. Consequentially, highly efficient MSCs promoted superior hyaline cartilage regeneration in vivo. This novel treatment method provides a basis for cell-based tissue engineering.",

author = "Choi, {Seong Mi} and Lee, {Kyoung Mi} and Ryu, {Seung Bae} and Park, {Yoo Jung} and Hwang, {Yeok Gu} and Dawoon Baek and Yoorim Choi and Park, {Kwang Hwan} and Park, {Ki Dong} and Lee, {Jin Woo}",

note = "Funding Information: This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. NRF-2016R1D1A1B03933182), and from the NRF grant funded by the Korea government (MSIP) (NRF-2018R1A2B2004529). Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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AU - Choi, Seong Mi

AU - Lee, Kyoung Mi

AU - Ryu, Seung Bae

AU - Park, Yoo Jung

AU - Hwang, Yeok Gu

AU - Baek, Dawoon

AU - Choi, Yoorim

AU - Park, Kwang Hwan

AU - Park, Ki Dong

AU - Lee, Jin Woo

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PY - 2018/9/1

Y1 - 2018/9/1

N2 - To investigate the functional effects of resveratrol (RSV) on mesenchymal stem cells (MSCs), we treated MSCs with RSV continuously during ex vivo expansion. MSCs were continuously treated with RSV from passage (P) 0 to P5. A proliferative capacity of RSV-treated MSCs was higher than that of non-treated MSCs and similar with P1-MSCs. Continuous treatment of RSV on MSCs increased the stemness and inhibited the senescence. During chondrogenic differentiation in vitro, RSV-treated MSCs had higher differentiation potential and reduced hypertrophic maturation, which are limitations for hyaline cartilage formation. The histological analysis of micromass demonstrated increased chondrogenic differentiation potential. We further explored the therapeutic effectiveness of this method in a rabbit osteochondral defect model. A rabbit osteochondral defect model was established to investigate the hyaline cartilage regeneration potential of RSV-treated MSCs. Moreover, the cartilage regeneration potential of RSV-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in RSV-treated MSCs compared with untreated MSCs. Sustained treatment of RSV on MSCs during ex vivo expansion resulted in the maintenance of stemness and enhanced chondrogenic differentiation potential. Consequentially, highly efficient MSCs promoted superior hyaline cartilage regeneration in vivo. This novel treatment method provides a basis for cell-based tissue engineering.

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Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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