Mussel Adhesion-Inspired Reverse Transfection Platform Enhances Osteogenic Differentiation and Bone Formation of Human Adipose-Derived Stem Cells

Jisoo Shin; Jung Ho Cho; Yoonhee Jin; Kisuk Yang; Jong Seung Lee; Hyun Ji Park; Hyung Seop Han; Jinkyu Lee; Hojeong Jeon; Heungsoo Shin; Seung Woo Cho

doi:10.1002/smll.201601868

Mussel Adhesion-Inspired Reverse Transfection Platform Enhances Osteogenic Differentiation and Bone Formation of Human Adipose-Derived Stem Cells

Jisoo Shin, Jung Ho Cho, Yoonhee Jin, Kisuk Yang, Jong Seung Lee, Hyun Ji Park, Hyung Seop Han, Jinkyu Lee, Hojeong Jeon, Heungsoo Shin, Seung Woo Cho

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

22 Citations (Scopus)

Abstract

Using small interfering RNA (siRNA) to regulate gene expression is an emerging strategy for stem cell manipulation to improve stem cell therapy. However, conventional methods of siRNA delivery into stem cells based on solution-mediated transfection are limited due to low transfection efficiency and insufficient duration of cell-siRNA contact during lengthy culturing protocols. To overcome these limitations, a bio-inspired polymer-mediated reverse transfection system is developed consisting of implantable poly(lactic-co-glycolic acid) (PLGA) scaffolds functionalized with siRNA-lipidoid nanoparticle (sLNP) complexes via polydopamine (pDA) coating. Immobilized sLNP complexes are stably maintained without any loss of siRNA on the pDA-coated scaffolds for 2 weeks, likely due to the formation of strong covalent bonds between amine groups of sLNP and catechol group of pDA. siRNA reverse transfection with the pDA-sLNP-PLGA system does not exhibit cytotoxicity and induces efficient silencing of an osteogenesis inhibitor gene in human adipose-derived stem cells (hADSCs), resulting in enhanced osteogenic differentiation of hADSCs. Finally, hADSCs osteogenically committed on the pDA-sLNP-PLGA scaffolds enhanced bone formation in a mouse model of critical-sized bone defect. Therefore, the bio-inspired reverse transfection system can provide an all-in-one platform for genetic modification, differentiation, and transplantation of stem cells, simultaneously enabling both stem cell manipulation and tissue engineering.

Original language	English
Pages (from-to)	6266-6278
Number of pages	13
Journal	Small
Volume	12
Issue number	45
DOIs	https://doi.org/10.1002/smll.201601868
Publication status	Published - 2016 Dec 7

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF-2015R1A2A1A15053771 and 2016M3C9A4921712) and the Translational Research Center for Protein Function Control (TRCP 2016R1A5A1004694) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea. This work was also supported by a grant from the Korea Health Technology R&D Project (HI13C1479) funded by the Ministry of Health and Welfare, Republic of Korea.

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

All Science Journal Classification (ASJC) codes

Biotechnology
Biomaterials
Chemistry(all)
Materials Science(all)

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10.1002/smll.201601868

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@article{cbcdb0da057144738cc86fcd0ac1a604,

title = "Mussel Adhesion-Inspired Reverse Transfection Platform Enhances Osteogenic Differentiation and Bone Formation of Human Adipose-Derived Stem Cells",

abstract = "Using small interfering RNA (siRNA) to regulate gene expression is an emerging strategy for stem cell manipulation to improve stem cell therapy. However, conventional methods of siRNA delivery into stem cells based on solution-mediated transfection are limited due to low transfection efficiency and insufficient duration of cell-siRNA contact during lengthy culturing protocols. To overcome these limitations, a bio-inspired polymer-mediated reverse transfection system is developed consisting of implantable poly(lactic-co-glycolic acid) (PLGA) scaffolds functionalized with siRNA-lipidoid nanoparticle (sLNP) complexes via polydopamine (pDA) coating. Immobilized sLNP complexes are stably maintained without any loss of siRNA on the pDA-coated scaffolds for 2 weeks, likely due to the formation of strong covalent bonds between amine groups of sLNP and catechol group of pDA. siRNA reverse transfection with the pDA-sLNP-PLGA system does not exhibit cytotoxicity and induces efficient silencing of an osteogenesis inhibitor gene in human adipose-derived stem cells (hADSCs), resulting in enhanced osteogenic differentiation of hADSCs. Finally, hADSCs osteogenically committed on the pDA-sLNP-PLGA scaffolds enhanced bone formation in a mouse model of critical-sized bone defect. Therefore, the bio-inspired reverse transfection system can provide an all-in-one platform for genetic modification, differentiation, and transplantation of stem cells, simultaneously enabling both stem cell manipulation and tissue engineering.",

author = "Jisoo Shin and Cho, {Jung Ho} and Yoonhee Jin and Kisuk Yang and Lee, {Jong Seung} and Park, {Hyun Ji} and Han, {Hyung Seop} and Jinkyu Lee and Hojeong Jeon and Heungsoo Shin and Cho, {Seung Woo}",

note = "Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF-2015R1A2A1A15053771 and 2016M3C9A4921712) and the Translational Research Center for Protein Function Control (TRCP 2016R1A5A1004694) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea. This work was also supported by a grant from the Korea Health Technology R&D Project (HI13C1479) funded by the Ministry of Health and Welfare, Republic of Korea. Publisher Copyright: {\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

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AU - Shin, Jisoo

AU - Cho, Jung Ho

AU - Jin, Yoonhee

AU - Yang, Kisuk

AU - Lee, Jong Seung

AU - Park, Hyun Ji

AU - Han, Hyung Seop

AU - Lee, Jinkyu

AU - Jeon, Hojeong

AU - Shin, Heungsoo

AU - Cho, Seung Woo

N1 - Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF-2015R1A2A1A15053771 and 2016M3C9A4921712) and the Translational Research Center for Protein Function Control (TRCP 2016R1A5A1004694) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea. This work was also supported by a grant from the Korea Health Technology R&D Project (HI13C1479) funded by the Ministry of Health and Welfare, Republic of Korea. Publisher Copyright: © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2016/12/7

Y1 - 2016/12/7

N2 - Using small interfering RNA (siRNA) to regulate gene expression is an emerging strategy for stem cell manipulation to improve stem cell therapy. However, conventional methods of siRNA delivery into stem cells based on solution-mediated transfection are limited due to low transfection efficiency and insufficient duration of cell-siRNA contact during lengthy culturing protocols. To overcome these limitations, a bio-inspired polymer-mediated reverse transfection system is developed consisting of implantable poly(lactic-co-glycolic acid) (PLGA) scaffolds functionalized with siRNA-lipidoid nanoparticle (sLNP) complexes via polydopamine (pDA) coating. Immobilized sLNP complexes are stably maintained without any loss of siRNA on the pDA-coated scaffolds for 2 weeks, likely due to the formation of strong covalent bonds between amine groups of sLNP and catechol group of pDA. siRNA reverse transfection with the pDA-sLNP-PLGA system does not exhibit cytotoxicity and induces efficient silencing of an osteogenesis inhibitor gene in human adipose-derived stem cells (hADSCs), resulting in enhanced osteogenic differentiation of hADSCs. Finally, hADSCs osteogenically committed on the pDA-sLNP-PLGA scaffolds enhanced bone formation in a mouse model of critical-sized bone defect. Therefore, the bio-inspired reverse transfection system can provide an all-in-one platform for genetic modification, differentiation, and transplantation of stem cells, simultaneously enabling both stem cell manipulation and tissue engineering.

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Mussel Adhesion-Inspired Reverse Transfection Platform Enhances Osteogenic Differentiation and Bone Formation of Human Adipose-Derived Stem Cells

Abstract

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