TY - JOUR
T1 - An Improved Understanding of the Pathophysiology of Pelvic Organ Prolapse
T2 - A 3D In Vitro Model under Static and Mechanical Loading Conditions
AU - van Velthoven, Melissa J.J.
AU - Gudde, Aksel N.
AU - van der Kruit, Marit
AU - van Loon, Malou P.C.
AU - Rasing, Lissy
AU - Wagener, Frank A.D.T.G.
AU - Roovers, Jan Paul
AU - Guler, Zeliha
AU - Kouwer, Paul H.J.
N1 - Funding Information: This project received public funding from ZonMw for the TOP project (grant number: 91218030). The authors acknowledge Dr. Behrad Shaghaghi for helping with the polymer synthesis and Dr. Tamar Wissing and Dr. Kim van der Heiden for their valuable input regarding the adjustments to enable 3D cell culturing using the Flexcell Tension System. Publisher Copyright: © 2024 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2024/3/25
Y1 - 2024/3/25
N2 - The suboptimal outcomes of pelvic organ prolapse (POP) surgery illustrate the demand for improved therapies. However, their development is hampered by the limited knowledge on the cellular pathophysiology of POP. Current investigations, that are limited to tissues and 2D in vitro models, provide highly inconclusive results on how the extracellular matrix (ECM) metabolism and fibroblasts are affected in POP. This study uses a physiologically relevant 3D in vitro model to investigate the cellular pathophysiology of POP by determining the differences between POP and non-POP fibroblasts on ECM metabolism, proliferation, and fibroblast-to-myofibroblast (FMT) transition. This model, based on the synthetic and biomimetic polyisocyanide hydrogel, enables the incorporation of mechanical loading, which simulates the forces exerted on the pelvic floor. Under static conditions, 3D cultured POP fibroblasts are less proliferative, undergo FMT, and exhibit lower collagen and elastin contents compared to non-POP fibroblasts. However, under mechanical loading, the differences between POP and non-POP fibroblasts are less pronounced. This study contributes to the development of more comprehensive models that can accurately mimic the POP pathophysiology, which will aid in an enhanced understanding and may contribute to improved therapies in the future.
AB - The suboptimal outcomes of pelvic organ prolapse (POP) surgery illustrate the demand for improved therapies. However, their development is hampered by the limited knowledge on the cellular pathophysiology of POP. Current investigations, that are limited to tissues and 2D in vitro models, provide highly inconclusive results on how the extracellular matrix (ECM) metabolism and fibroblasts are affected in POP. This study uses a physiologically relevant 3D in vitro model to investigate the cellular pathophysiology of POP by determining the differences between POP and non-POP fibroblasts on ECM metabolism, proliferation, and fibroblast-to-myofibroblast (FMT) transition. This model, based on the synthetic and biomimetic polyisocyanide hydrogel, enables the incorporation of mechanical loading, which simulates the forces exerted on the pelvic floor. Under static conditions, 3D cultured POP fibroblasts are less proliferative, undergo FMT, and exhibit lower collagen and elastin contents compared to non-POP fibroblasts. However, under mechanical loading, the differences between POP and non-POP fibroblasts are less pronounced. This study contributes to the development of more comprehensive models that can accurately mimic the POP pathophysiology, which will aid in an enhanced understanding and may contribute to improved therapies in the future.
KW - extracellular matrix
KW - fibroblast-to-myofibroblast transition
KW - fibroblasts
KW - in vitro models
KW - mechanical loading
KW - pelvic organ prolapse
UR - http://www.scopus.com/inward/record.url?scp=85183092940&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/adhm.202302905
DO - https://doi.org/10.1002/adhm.202302905
M3 - Article
C2 - 38219051
SN - 2192-2640
VL - 13
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 8
M1 - 2302905
ER -