“…Some dead EthD-1-positive cells were observed on the PLGA-only sponge. It has previously been observed that cell morphology can be controlled by the viscosity of substrates and that gel stiffness can affect cell proliferation [ 72 , 73 ]. The cells in the 50% HA hydrogel showed better spreading and increased cell number because 50% HA had a lower viscosity (Figure S 2 ).…”
Background
Premature ovarian insufficiency (POI) is one of the most serious side effects of chemotherapy in young cancer survivors. It may not only reduce fecundity but also affect lifelong health. There is no standard therapy for preserving ovarian health after chemotherapy. Recently, administration of embryonic stem cell-derived mesenchymal progenitor cells (ESC-MPCs) has been considered a new therapeutic option for preventing POI. However, the previous method of directly injecting cells into the veins of patients exhibits low efficacy and safety. This study aimed to develop safe and effective local delivery methods for the prevention of POI using two types of bioinspired scaffolds.
Methods
Female mice received intraperitoneal cisplatin for 10 days. On day 11, human ESC-MPCs were delivered through systemic administration using intravenous injection or local administration using intradermal injection and intradermal transplantation with a PLGA/MH sponge or hyaluronic acid (HA) gel (GEL) type of scaffold. PBS was injected intravenously as a negative control. Ovarian function and fertility were evaluated 4 weeks after transplantation. Follicle development was observed using hematoxylin and eosin staining. The plasma levels of sex hormones were measured using ELISA. Expression levels of anti-Müllerian hormone (AMH) and ki-67 were detected using immunostaining, and the quality of oocytes and embryos was evaluated after in vitro fertilization. The estrous cycles were observed at 2 months after transplantation.
Results
The local administration of human ESC-MPCs using the bioinspired scaffold to the backs of mice effectively prolonged the cell survival rate in vivo. The HA GEL group exhibited the best recovered ovarian functions, including a significantly increased number of ovarian reserves, estrogen levels, and AMH levels and decreased apoptotic levels. Furthermore, the HA GEL group showed improved quality of oocytes and embryos and estrous cycle regularity.
Conclusions
HA GEL scaffolds can be used as new delivery platforms for ESC-MPC therapy, and this method may provide a novel option for the clinical treatment of chemotherapy-induced POI.
“…Some dead EthD-1-positive cells were observed on the PLGA-only sponge. It has previously been observed that cell morphology can be controlled by the viscosity of substrates and that gel stiffness can affect cell proliferation [ 72 , 73 ]. The cells in the 50% HA hydrogel showed better spreading and increased cell number because 50% HA had a lower viscosity (Figure S 2 ).…”
Background
Premature ovarian insufficiency (POI) is one of the most serious side effects of chemotherapy in young cancer survivors. It may not only reduce fecundity but also affect lifelong health. There is no standard therapy for preserving ovarian health after chemotherapy. Recently, administration of embryonic stem cell-derived mesenchymal progenitor cells (ESC-MPCs) has been considered a new therapeutic option for preventing POI. However, the previous method of directly injecting cells into the veins of patients exhibits low efficacy and safety. This study aimed to develop safe and effective local delivery methods for the prevention of POI using two types of bioinspired scaffolds.
Methods
Female mice received intraperitoneal cisplatin for 10 days. On day 11, human ESC-MPCs were delivered through systemic administration using intravenous injection or local administration using intradermal injection and intradermal transplantation with a PLGA/MH sponge or hyaluronic acid (HA) gel (GEL) type of scaffold. PBS was injected intravenously as a negative control. Ovarian function and fertility were evaluated 4 weeks after transplantation. Follicle development was observed using hematoxylin and eosin staining. The plasma levels of sex hormones were measured using ELISA. Expression levels of anti-Müllerian hormone (AMH) and ki-67 were detected using immunostaining, and the quality of oocytes and embryos was evaluated after in vitro fertilization. The estrous cycles were observed at 2 months after transplantation.
Results
The local administration of human ESC-MPCs using the bioinspired scaffold to the backs of mice effectively prolonged the cell survival rate in vivo. The HA GEL group exhibited the best recovered ovarian functions, including a significantly increased number of ovarian reserves, estrogen levels, and AMH levels and decreased apoptotic levels. Furthermore, the HA GEL group showed improved quality of oocytes and embryos and estrous cycle regularity.
Conclusions
HA GEL scaffolds can be used as new delivery platforms for ESC-MPC therapy, and this method may provide a novel option for the clinical treatment of chemotherapy-induced POI.
“…Second harmonic generation (SHG), in which two lower energy photons are upconverted to a single high-energy photon with twice the energy, occurs in ordered non-centrosymmetric materials. Notably fibrillar collagen, a key component of the ECM, exhibits a strong SHG response [ 237 ] which can be exploited for label-free visualization tissue remodelling in response to PM exposure and structural imaging of lung tissue scaffolds [ 238 ] and other collagen-based hydrogels [ 239 ]. SHG microscopy has also been applied to visualize other biomolecular assemblies such as microtubules [ 240 ].…”
Section: High-resolution Imaging Of Respiratory Modelsmentioning
Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive,
in vitro
respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of
in vitro
imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art
in vitro
respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell–pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.
“…SHG has also been used to investigate collagen remodeling and the role of enzymes released from the cells in crosslinking collagen fibers [ 148 ]. Collagen fibers that are newly deposited by cells encapsulated in alginate hydrogels are also readily visualized by SHG [ 149 ].…”
The extracellular matrix (ECM) is a three-dimensional, acellular scaffold of living tissues. Incorporating the ECM into cell culture models is a goal of cell biology studies and requires biocompatible materials that can mimic the ECM. Among such materials are hydrogels: polymeric networks that derive most of their mass from water. With the tuning of their properties, these polymer networks can resemble living tissues. The microarchitectural properties of hydrogels, such as porosity, pore size, fiber length, and surface topology can determine cell plasticity. The adequate characterization of these parameters requires reliable and reproducible methods. However, most methods were historically standardized using other biological specimens, such as 2D cell cultures, biopsies, or even animal models. Therefore, their translation comes with technical limitations when applied to hydrogel-based cell culture systems. In our current work, we have reviewed the most common techniques employed in the characterization of hydrogel microarchitectures. Our review provides a concise description of the underlying principles of each method and summarizes the collective data obtained from cell-free and cell-loaded hydrogels. The advantages and limitations of each technique are discussed, and comparisons are made. The information presented in our current work will be of interest to researchers who employ hydrogels as platforms for cell culture, 3D bioprinting, and other fields within hydrogel-based research.
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