Remodeling of Aligned Fibrous Extracellular Matrix by Encapsulated Cells Under Mechanical Stretching

Pei, Dandan; Wang, Meng-Qi; Li, Wenfang; Li, Meiwen; Liu, Qian; Ding, Rui; Zhao, Jing; Li, Ang; Xu, Feng; Jin, Guorui

doi:10.2139/ssrn.3542979

Cited by 2 publications

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“…We speculate that ovarian stretching modifies the local mechanical stress and induces a mechano-regulation feedback that leads to ECM rearrangement in order to maintain overall form and function. A similar stretch-induced ECM remodelling has been reported in cultured cells from human and mouse periodontal ligament stem cells and lung, cardiac and scleral fibroblasts (Shelton and Rada, 2007;Herum et al, 2017;Pei et al, 2020;Xie et al, 2020), while mechanical stretching of human mammary and canine kidney epithelial cells has been linked with low cell density, modulation of Yesassociated protein/transcriptional coactivator with PDZ-binding motif activity and cell cycle entry (Aragona et al, 2013;Gudipaty et al, 2017). Another possibility is that in vitro culture indirectly triggers ECM remodelling via phosphatidylinositol 3-kinase/protein kinase B and Hippo disturbance as well as an imbalance of ECM-regulating enzymes.…”

Section: Discussionsupporting

confidence: 75%

Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix duringin vitroculture

et al. 2023

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STUDY QUESTION How does in vitro culture alter the human ovarian cortical extracellular matrix (ECM) network structure? SUMMARY ANSWER The ECM composition and architecture vary in the different layers of the ovarian cortex and are remodelled during in vitro culture. WHAT IS KNOWN ALREADY The ovarian ECM is the scaffold within which follicles and stromal cells are organized. Its composition and structural properties constantly evolve to accommodate follicle development and expansion. Tissue preparation for culture of primordial follicles within the native ECM involves mechanical loosening; this induces undefined modifications in the ECM network and alters cell–cell contact, leading to spontaneous follicle activation. STUDY DESIGN, SIZE, DURATION Fresh ovarian cortical biopsies were obtained from six women aged 28–38 years (mean ± SD: 32.7 ± 4.1 years) at elective caesarean section. Biopsies were cut into fragments of ∼4 × 1 × 1 mm and cultured for 0, 2, 4, or 6 days (D). PARTICIPANTS/MATERIALS, SETTING, METHODS Primordial follicle activation, stromal cell density, and ECM-related protein (collagen, elastin, fibronectin, laminin) positive area in the entire cortex were quantified at each time point using histological and immunohistological analysis. Collagen and elastin content, collagen fibre characteristics, and follicle distribution within the tissue were further quantified within each layer of the human ovarian cortex, namely the outer cortex, the mid-cortex, and the cortex–medulla junction regions. MAIN RESULTS AND THE ROLE OF CHANCE Primordial follicle activation occurred concomitantly with a loosening of the ovarian cortex during culture, characterized by an early decrease in stromal cell density from 3.6 ± 0.2 × 106 at day 0 (D0) to 2.8 ± 0.1 × 106 cells/mm3 at D2 (P = 0.033) and a dynamic remodelling of the ECM. Notably, collagen content gradually fell from 55.5 ± 1.7% positive area at D0 to 42.3 ± 1.1% at D6 (P = 0.001), while elastin increased from 1.1 ± 0.2% at D0 to 1.9 ± 0.1% at D6 (P = 0.001). Fibronectin and laminin content remained stable. Moreover, collagen and elastin distribution were uneven throughout the cortex and during culture. Analysis at the sub-region level showed that collagen deposition was maximal in the outer cortex and the lowest in the mid-cortex (69.4 ± 1.2% versus 53.8 ± 0.8% positive area, respectively, P < 0.0001), and cortical collagen staining overall decreased from D0 to D2 (65.2 ± 2.4% versus 60.6 ± 1.8%, P = 0.033) then stabilized. Elastin showed the converse distribution, being most concentrated at the cortex–medulla junction (3.7 ± 0.6% versus 0.9 ± 0.2% in the outer cortex, P < 0.0001), and cortical elastin peaked at D6 compared to D0 (3.1 ± 0.5% versus 1.3 ± 0.2%, P < 0.0001). This was corroborated by a specific signature of the collagen fibre type across the cortex, indicating a distinct phenotype of the ovarian cortical ECM depending on region and culture period that might be responsible for the spatio-temporal and developmental pattern of follicular distribution observed within the cortex. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Ovarian cortical biopsies were obtained from women undergoing caesarean sections. As such, the data obtained may not accurately reflect the ECM distribution and structure of non-pregnant women. WIDER IMPLICATIONS OF THE FINDINGS Clarifying the composition and architecture signature of the human ovarian cortical ECM provides a foundation for further exploration of ovarian microenvironments. It is also critical for understanding the ECM–follicle interactions regulating follicle quiescence and awakening, leading to improvements in both in vitro activation and in vitro growth techniques. STUDY FUNDING/COMPETING INTEREST(S) Medical Research Council grant MR/R003246/1 and Wellcome Trust Collaborative Award in Science: 215625/Z/19/Z. The authors have no conflicts to declare. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionsupporting

confidence: 75%

Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix duringin vitroculture

et al. 2023

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“…To mimic the ECM, hydrogels have been widely used in 3D cell culture. From the aspects of mechanical stretching, hydrogels can not only transmit stretch forces to the resident cells, forcing cells to stretch, but also respond to mechanical stretch itself via structural remodeling and biochemical molecule regulation, all of which can have profound effects on cell behaviors ( Vader et al, 2009 ; Gaul et al, 2018 ; Liu et al, 2020 ; Pei et al, 2020 ). It is therefore reasonable to include mechanical, structural and biochemical considerations when engineering hydrogels for mechanical stretching of cells in three dimensions ( Figure 3 ; Li et al, 2017 ; Davidson et al, 2020 ).…”

Section: Engineering Biomaterials For Mechanical Stretching Of Cells mentioning

confidence: 99%

Engineering Biomaterials and Approaches for Mechanical Stretching of Cells in Three Dimensions

Zhang

Huang

2020

Front. Bioeng. Biotechnol.

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Mechanical stretch is widely experienced by cells of different tissues in the human body and plays critical roles in regulating their behaviors. Numerous studies have been devoted to investigating the responses of cells to mechanical stretch, providing us with fruitful findings. However, these findings have been mostly observed from two-dimensional studies and increasing evidence suggests that cells in three dimensions may behave more closely to their in vivo behaviors. While significant efforts and progresses have been made in the engineering of biomaterials and approaches for mechanical stretching of cells in three dimensions, much work remains to be done. Here, we briefly review the state-of-the-art researches in this area, with focus on discussing biomaterial considerations and stretching approaches. We envision that with the development of advanced biomaterials, actuators and microengineering technologies, more versatile and predictive three-dimensional cell stretching models would be available soon for extensive applications in such fields as mechanobiology, tissue engineering, and drug screening.

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Remodeling of Aligned Fibrous Extracellular Matrix by Encapsulated Cells Under Mechanical Stretching

Cited by 2 publications

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Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix duringin vitroculture

Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix duringin vitroculture

Engineering Biomaterials and Approaches for Mechanical Stretching of Cells in Three Dimensions

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