Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amylo...

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Main Authors: Sang Eon Park, Hyeong Seop Kim, Soo Jin Kwon, Min-Jeong Kim, Suk-joo Choi, Soo-young Oh, Gyu Ha Ryu, Hong Bae Jeon, Duk L. Na, Jong Wook Chang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/6660186
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author Sang Eon Park
Hyeong Seop Kim
Soo Jin Kwon
Min-Jeong Kim
Suk-joo Choi
Soo-young Oh
Gyu Ha Ryu
Hong Bae Jeon
Duk L. Na
Jong Wook Chang
author_facet Sang Eon Park
Hyeong Seop Kim
Soo Jin Kwon
Min-Jeong Kim
Suk-joo Choi
Soo-young Oh
Gyu Ha Ryu
Hong Bae Jeon
Duk L. Na
Jong Wook Chang
author_sort Sang Eon Park
collection DOAJ
description Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta- (Aβ-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of Aβ and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.
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spelling doaj-art-f2240fe6a1414375b818048bb953492c2025-02-03T01:05:28ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/66601866660186Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic EffectsSang Eon Park0Hyeong Seop Kim1Soo Jin Kwon2Min-Jeong Kim3Suk-joo Choi4Soo-young Oh5Gyu Ha Ryu6Hong Bae Jeon7Duk L. Na8Jong Wook Chang9Stem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of KoreaStem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of KoreaStem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of KoreaStem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Medical Device Management and Research, SAIHST, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaStem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of KoreaStem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Republic of KoreaStem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of KoreaMesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta- (Aβ-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of Aβ and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.http://dx.doi.org/10.1155/2021/6660186
spellingShingle Sang Eon Park
Hyeong Seop Kim
Soo Jin Kwon
Min-Jeong Kim
Suk-joo Choi
Soo-young Oh
Gyu Ha Ryu
Hong Bae Jeon
Duk L. Na
Jong Wook Chang
Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects
Stem Cells International
title Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects
title_full Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects
title_fullStr Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects
title_full_unstemmed Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects
title_short Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects
title_sort exposure of mesenchymal stem cells to an alzheimer s disease environment enhances therapeutic effects
url http://dx.doi.org/10.1155/2021/6660186
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