Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model

Secondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were e...

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Main Authors: Liru Hu, Nian Zhang, Chengzhi Zhao, Jian Pan
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Experimental Biology and Medicine
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Online Access:https://www.ebm-journal.org/articles/10.3389/ebm.2024.10295/full
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author Liru Hu
Nian Zhang
Chengzhi Zhao
Jian Pan
author_facet Liru Hu
Nian Zhang
Chengzhi Zhao
Jian Pan
author_sort Liru Hu
collection DOAJ
description Secondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were engineered in vitro and then transplanted into the site of lymphedema. Yes-associated protein (YAP), a crucial regulator of Hippo pathway, plays an important role in regulating stem cell functions. We examined the YAP expression in a mouse tail lymphedema model, and found that transplanted ADSCs exhibited high expression level of YAP and a large number of YAP positive cells existed in lymphedema environment. In vitro, the downregulation of YAP in ADSCs resulted in higher expression levels of genes related to lymphangiogenesis such as Lyve-1, VEGFR-3 and Prox-1. In vivo, YAP-engineered ADSCs generated abundant VEGFR-3-positive lymphatic vessels and significantly improved subcutaneous fibrosis. These results indicated that the transplantation of pre-engineered ADSCs by manipulating YAP is a promising strategy for lymphatic reconstruction.
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spelling doaj-art-895d0f6af289430f877a4484f1486af02024-11-20T04:11:09ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992024-11-0124910.3389/ebm.2024.1029510295Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail modelLiru HuNian ZhangChengzhi ZhaoJian PanSecondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were engineered in vitro and then transplanted into the site of lymphedema. Yes-associated protein (YAP), a crucial regulator of Hippo pathway, plays an important role in regulating stem cell functions. We examined the YAP expression in a mouse tail lymphedema model, and found that transplanted ADSCs exhibited high expression level of YAP and a large number of YAP positive cells existed in lymphedema environment. In vitro, the downregulation of YAP in ADSCs resulted in higher expression levels of genes related to lymphangiogenesis such as Lyve-1, VEGFR-3 and Prox-1. In vivo, YAP-engineered ADSCs generated abundant VEGFR-3-positive lymphatic vessels and significantly improved subcutaneous fibrosis. These results indicated that the transplantation of pre-engineered ADSCs by manipulating YAP is a promising strategy for lymphatic reconstruction.https://www.ebm-journal.org/articles/10.3389/ebm.2024.10295/fullYAPverteporfinADSCslymphedemalymphangiogenesis
spellingShingle Liru Hu
Nian Zhang
Chengzhi Zhao
Jian Pan
Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model
Experimental Biology and Medicine
YAP
verteporfin
ADSCs
lymphedema
lymphangiogenesis
title Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model
title_full Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model
title_fullStr Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model
title_full_unstemmed Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model
title_short Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail model
title_sort engineering adscs by manipulating yap for lymphedema treatment in a mouse tail model
topic YAP
verteporfin
ADSCs
lymphedema
lymphangiogenesis
url https://www.ebm-journal.org/articles/10.3389/ebm.2024.10295/full
work_keys_str_mv AT liruhu engineeringadscsbymanipulatingyapforlymphedematreatmentinamousetailmodel
AT nianzhang engineeringadscsbymanipulatingyapforlymphedematreatmentinamousetailmodel
AT chengzhizhao engineeringadscsbymanipulatingyapforlymphedematreatmentinamousetailmodel
AT jianpan engineeringadscsbymanipulatingyapforlymphedematreatmentinamousetailmodel