Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family

Bin Wang; Mengru Pang; Yancheng Song; Haixing Wang; Pan Qi; Shanshan Bai; Xiaoxuan Lei; Shikun Wei; Zhixian Zong; Sien Lin; Xiaoting Zhang; Xiaotong Cen; Xia Wang; Yongkang Yang; Yuan Li; Yan Wang; Hongjie Xu; Lin Huang; Micky Tortorella; Biao Cheng; Yukwai Lee; Dajiang Qin; Gang Li

doi:10.1002/btm2.10354

Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family

Bin Wang^*, Mengru Pang, Yancheng Song, Haixing Wang, Pan Qi, Shanshan Bai, Xiaoxuan Lei, Shikun Wei, Zhixian Zong, Sien Lin, Xiaoting Zhang, Xiaotong Cen, Xia Wang, Yongkang Yang, Yuan Li, Yan Wang, Hongjie Xu, Lin Huang, Micky Tortorella, Biao ChengYukwai Lee, Dajiang Qin, Gang Li

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

Original language	English
Article number	e10354
Number of pages	20
Journal	Bioengineering and Translational Medicine
Volume	8
Issue number	1
Early online date	21 Jun 2022
DOIs	https://doi.org/10.1002/btm2.10354
Publication status	Published - Jan 2023

Bibliographical note

Funding Information:
Guangzhou Municipal Science and Technology Bureau, CHINA, Grant/Award Number: 202102021247; Hong Kong Innovation Technology Commission Funds, Grant/Award Number: PRP/050/19FX; Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Grant/Award Number: SMART program; Research Grants Council, University Grants Committee of Hong Kong Special Administrative, Grant/Award Numbers: AoE/M‐402/20, T13‐402/17‐N; Key Laboratory of Guangdong Higher Education Institutes, Grant/Award Numbers: 19FX, T13‐402 Funding information

Funding Information:
This work was fully supported by grants from the University Grants Committee, Research Grants Council of the Hong Kong Special Administrative Region, China (T13‐402/17‐N and AoE/M‐402/20); partially supported by grants from Hong Kong Innovation Technology Commission Funds (PRP/050/19FX). This study also received support from the SMART program, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong. This work was also supported by grants from Guangzhou science and technology bureau, CHINA (202102021247).

Publisher Copyright:
© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

Funding

Guangzhou Municipal Science and Technology Bureau, CHINA, Grant/Award Number: 202102021247; Hong Kong Innovation Technology Commission Funds, Grant/Award Number: PRP/050/19FX; Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Grant/Award Number: SMART program; Research Grants Council, University Grants Committee of Hong Kong Special Administrative, Grant/Award Numbers: AoE/M‐402/20, T13‐402/17‐N; Key Laboratory of Guangdong Higher Education Institutes, Grant/Award Numbers: 19FX, T13‐402 Funding information This work was fully supported by grants from the University Grants Committee, Research Grants Council of the Hong Kong Special Administrative Region, China (T13‐402/17‐N and AoE/M‐402/20); partially supported by grants from Hong Kong Innovation Technology Commission Funds (PRP/050/19FX). This study also received support from the SMART program, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong. This work was also supported by grants from Guangzhou science and technology bureau, CHINA (202102021247).

Funders	Funder number
University Grants Committee, Research Grants Council of the Hong Kong Special Administrative Region, China	AoE/M-402/20, T13-402/17-N
Chinese University of Hong Kong
Innovation and Technology Commission - Hong Kong
Guangzhou Municipal Science and Technology Bureau	202102021247

Keywords

bioreactor
diabetic wound healing
fetal mesenchymal stem cell secretome
PLGA particles
quality control

UN SDGs

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

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10.1002/btm2.10354

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Wang, B., Pang, M., Song, Y., Wang, H., Qi, P., Bai, S., Lei, X., Wei, S., Zong, Z., Lin, S., Zhang, X., Cen, X., Wang, X., Yang, Y., Li, Y., Wang, Y., Xu, H., Huang, L., Tortorella, M., ... Li, G. (2023). Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family. Bioengineering and Translational Medicine, 8(1), Article e10354. https://doi.org/10.1002/btm2.10354

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title = "Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family",

abstract = "The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.",

keywords = "bioreactor, diabetic wound healing, fetal mesenchymal stem cell secretome, PLGA particles, quality control",

author = "Bin Wang and Mengru Pang and Yancheng Song and Haixing Wang and Pan Qi and Shanshan Bai and Xiaoxuan Lei and Shikun Wei and Zhixian Zong and Sien Lin and Xiaoting Zhang and Xiaotong Cen and Xia Wang and Yongkang Yang and Yuan Li and Yan Wang and Hongjie Xu and Lin Huang and Micky Tortorella and Biao Cheng and Yukwai Lee and Dajiang Qin and Gang Li",

note = "Funding Information: Guangzhou Municipal Science and Technology Bureau, CHINA, Grant/Award Number: 202102021247; Hong Kong Innovation Technology Commission Funds, Grant/Award Number: PRP/050/19FX; Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Grant/Award Number: SMART program; Research Grants Council, University Grants Committee of Hong Kong Special Administrative, Grant/Award Numbers: AoE/M‐402/20, T13‐402/17‐N; Key Laboratory of Guangdong Higher Education Institutes, Grant/Award Numbers: 19FX, T13‐402 Funding information Funding Information: This work was fully supported by grants from the University Grants Committee, Research Grants Council of the Hong Kong Special Administrative Region, China (T13‐402/17‐N and AoE/M‐402/20); partially supported by grants from Hong Kong Innovation Technology Commission Funds (PRP/050/19FX). This study also received support from the SMART program, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong. This work was also supported by grants from Guangzhou science and technology bureau, CHINA (202102021247). Publisher Copyright: {\textcopyright} 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.",

year = "2023",

month = jan,

doi = "10.1002/btm2.10354",

language = "English",

volume = "8",

journal = "Bioengineering and Translational Medicine",

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Wang, B, Pang, M, Song, Y, Wang, H, Qi, P, Bai, S, Lei, X, Wei, S, Zong, Z, Lin, S, Zhang, X, Cen, X, Wang, X, Yang, Y, Li, Y, Wang, Y, Xu, H, Huang, L, Tortorella, M, Cheng, B, Lee, Y, Qin, D & Li, G 2023, 'Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family', Bioengineering and Translational Medicine, vol. 8, no. 1, e10354. https://doi.org/10.1002/btm2.10354

TY - JOUR

T1 - Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family

AU - Wang, Bin

AU - Pang, Mengru

AU - Song, Yancheng

AU - Wang, Haixing

AU - Qi, Pan

AU - Bai, Shanshan

AU - Lei, Xiaoxuan

AU - Wei, Shikun

AU - Zong, Zhixian

AU - Lin, Sien

AU - Zhang, Xiaoting

AU - Cen, Xiaotong

AU - Wang, Xia

AU - Yang, Yongkang

AU - Li, Yuan

AU - Wang, Yan

AU - Xu, Hongjie

AU - Huang, Lin

AU - Tortorella, Micky

AU - Cheng, Biao

AU - Lee, Yukwai

AU - Qin, Dajiang

AU - Li, Gang

N1 - Funding Information: Guangzhou Municipal Science and Technology Bureau, CHINA, Grant/Award Number: 202102021247; Hong Kong Innovation Technology Commission Funds, Grant/Award Number: PRP/050/19FX; Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Grant/Award Number: SMART program; Research Grants Council, University Grants Committee of Hong Kong Special Administrative, Grant/Award Numbers: AoE/M‐402/20, T13‐402/17‐N; Key Laboratory of Guangdong Higher Education Institutes, Grant/Award Numbers: 19FX, T13‐402 Funding information Funding Information: This work was fully supported by grants from the University Grants Committee, Research Grants Council of the Hong Kong Special Administrative Region, China (T13‐402/17‐N and AoE/M‐402/20); partially supported by grants from Hong Kong Innovation Technology Commission Funds (PRP/050/19FX). This study also received support from the SMART program, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong. This work was also supported by grants from Guangzhou science and technology bureau, CHINA (202102021247). Publisher Copyright: © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

PY - 2023/1

Y1 - 2023/1

N2 - The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

AB - The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

KW - bioreactor

KW - diabetic wound healing

KW - fetal mesenchymal stem cell secretome

KW - PLGA particles

KW - quality control

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DO - 10.1002/btm2.10354

M3 - Article

AN - SCOPUS:85132134355

SN - 2380-6761

VL - 8

JO - Bioengineering and Translational Medicine

JF - Bioengineering and Translational Medicine

IS - 1

M1 - e10354

ER -

Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family

Abstract

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Keywords

UN SDGs

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