Extracellular vesicles from thapsigargin‐treated mesenchymal stem cells ameliorated experimental colitis via enhanced immunomodulatory properties

Hansol Joo; Mi Kyung Oh; Ji Yeon Kang; Hyun Sung Park; Dong Hoon Chae; Jieun Kim; Jong Hee Lee; Hee Min Yoo; Uimook Choi; Do Kyun Kim; Hakmo Lee; Sungjoo Kim; Kyung Rok Yu

doi:10.3390/biomedicines9020209

Extracellular vesicles from thapsigargin‐treated mesenchymal stem cells ameliorated experimental colitis via enhanced immunomodulatory properties

Hansol Joo, Mi Kyung Oh, Ji Yeon Kang, Hyun Sung Park, Dong Hoon Chae, Jieun Kim, Jong Hee Lee, Hee Min Yoo, Uimook Choi, Do Kyun Kim, Hakmo Lee, Sungjoo Kim, Kyung Rok Yu

Department of Biomedicine & Health Science

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

16 Scopus citations

Abstract

Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune‐mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)‐primed human Wharton’s jelly‐derived MSCs (WJ‐MSCs). EVs from TSG‐primed WJ‐MSCs (TSG‐EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor‐β1 (TGFβ), cyclooxygenase‐2 (COX2), and especially indoleamine 2,3‐dioxygenase (IDO), compared to control EVs. TSG‐EV showed a significantly enhanced immunosuppressive effect on human peripheral blood‐derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2‐type macrophage were enriched compared to a control EV‐treated group. Furthermore, TSG‐EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2‐type macrophages in colitic colons of a TSG‐EV‐treated mouse suggests an anti‐inflammatory effect of TSG‐EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ‐MSCs, and TSG‐EV may provide a new therapeutic approach for treatment of colitis.

Original language	English
Article number	209
Pages (from-to)	1-17
Number of pages	17
Journal	Biomedicines
Volume	9
Issue number	2
DOIs	https://doi.org/10.3390/biomedicines9020209
State	Published - Feb 2021

Bibliographical note

Funding Information:
Funding: This research was supported by the Basic Research Program through the National Re‐ search Foundation of Korea (NRF) (2019R1C1C1008896) funded by the Korean government.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Colitis model
EVs
Immunomodulatory property
Indoleamine 2,3‐dioxygenase (IDO)
Mesenchymal stem cells
Thapsigargin

UN SDGs

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

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10.3390/biomedicines9020209

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Joo, H., Oh, M. K., Kang, J. Y., Park, H. S., Chae, D. H., Kim, J., Lee, J. H., Yoo, H. M., Choi, U., Kim, D. K., Lee, H., Kim, S., & Yu, K. R. (2021). Extracellular vesicles from thapsigargin‐treated mesenchymal stem cells ameliorated experimental colitis via enhanced immunomodulatory properties. Biomedicines, 9(2), 1-17. Article 209. https://doi.org/10.3390/biomedicines9020209

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abstract = "Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune‐mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)‐primed human Wharton{\textquoteright}s jelly‐derived MSCs (WJ‐MSCs). EVs from TSG‐primed WJ‐MSCs (TSG‐EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor‐β1 (TGFβ), cyclooxygenase‐2 (COX2), and especially indoleamine 2,3‐dioxygenase (IDO), compared to control EVs. TSG‐EV showed a significantly enhanced immunosuppressive effect on human peripheral blood‐derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2‐type macrophage were enriched compared to a control EV‐treated group. Furthermore, TSG‐EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2‐type macrophages in colitic colons of a TSG‐EV‐treated mouse suggests an anti‐inflammatory effect of TSG‐EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ‐MSCs, and TSG‐EV may provide a new therapeutic approach for treatment of colitis.",

keywords = "Colitis model, EVs, Immunomodulatory property, Indoleamine 2,3‐dioxygenase (IDO), Mesenchymal stem cells, Thapsigargin",

author = "Hansol Joo and Oh, {Mi Kyung} and Kang, {Ji Yeon} and Park, {Hyun Sung} and Chae, {Dong Hoon} and Jieun Kim and Lee, {Jong Hee} and Yoo, {Hee Min} and Uimook Choi and Kim, {Do Kyun} and Hakmo Lee and Sungjoo Kim and Yu, {Kyung Rok}",

note = "Funding Information: Funding: This research was supported by the Basic Research Program through the National Re‐ search Foundation of Korea (NRF) (2019R1C1C1008896) funded by the Korean government. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Oh, Mi Kyung

AU - Kang, Ji Yeon

AU - Park, Hyun Sung

AU - Chae, Dong Hoon

AU - Kim, Jieun

AU - Lee, Jong Hee

AU - Yoo, Hee Min

AU - Choi, Uimook

AU - Kim, Do Kyun

AU - Lee, Hakmo

AU - Kim, Sungjoo

AU - Yu, Kyung Rok

N1 - Funding Information: Funding: This research was supported by the Basic Research Program through the National Re‐ search Foundation of Korea (NRF) (2019R1C1C1008896) funded by the Korean government. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/2

Y1 - 2021/2

N2 - Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune‐mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)‐primed human Wharton’s jelly‐derived MSCs (WJ‐MSCs). EVs from TSG‐primed WJ‐MSCs (TSG‐EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor‐β1 (TGFβ), cyclooxygenase‐2 (COX2), and especially indoleamine 2,3‐dioxygenase (IDO), compared to control EVs. TSG‐EV showed a significantly enhanced immunosuppressive effect on human peripheral blood‐derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2‐type macrophage were enriched compared to a control EV‐treated group. Furthermore, TSG‐EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2‐type macrophages in colitic colons of a TSG‐EV‐treated mouse suggests an anti‐inflammatory effect of TSG‐EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ‐MSCs, and TSG‐EV may provide a new therapeutic approach for treatment of colitis.

AB - Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune‐mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)‐primed human Wharton’s jelly‐derived MSCs (WJ‐MSCs). EVs from TSG‐primed WJ‐MSCs (TSG‐EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor‐β1 (TGFβ), cyclooxygenase‐2 (COX2), and especially indoleamine 2,3‐dioxygenase (IDO), compared to control EVs. TSG‐EV showed a significantly enhanced immunosuppressive effect on human peripheral blood‐derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2‐type macrophage were enriched compared to a control EV‐treated group. Furthermore, TSG‐EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2‐type macrophages in colitic colons of a TSG‐EV‐treated mouse suggests an anti‐inflammatory effect of TSG‐EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ‐MSCs, and TSG‐EV may provide a new therapeutic approach for treatment of colitis.

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KW - EVs

KW - Immunomodulatory property

KW - Indoleamine 2,3‐dioxygenase (IDO)

KW - Mesenchymal stem cells

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SN - 2227-9059

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JO - Biomedicines

JF - Biomedicines

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ER -

Extracellular vesicles from thapsigargin‐treated mesenchymal stem cells ameliorated experimental colitis via enhanced immunomodulatory properties

Abstract

Bibliographical note

Keywords

UN SDGs

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