Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in the PLOD2 Gene DOI Open Access
Olga I. Bolshakova,

Evgenia M. Latypova,

Artem E. Komissarov

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13379 - 13379

Published: Dec. 13, 2024

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis known be associated with mutations the FKBP10 (FKBP prolyl isomerase 10) PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role biosynthesis of type I collagen, which turn affects structure strength connective tissues bones body. Mutations are disturbances both primary collagen chain its post-translational formation, but mechanism lead phenotypes has not been determined, only because small number patients who come attention researchers also lack disease models. In our work, we investigated cellular effects two forms wild-type gene, as well gene homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line human skin fibroblasts (DF2 line). localization protein cells caused expression different isoforms—long, short, long mutation—were analyzed. addition, results transcriptome analysis patient syndrome, whom this was detected, presented.

Language: Английский

Mesenchymal Stem Cell-Derived Extracellular Vesicles Improve Survival and Enhance Hematopoietic Recovery in Mice Exposed to High-Dose Irradiation DOI
Sicheng Wen, Mark S. Dooner, Mandy Pereira

et al.

Stem Cells and Development, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Exposure to high-dose radiation often results in hematopoietic acute syndromes, leading early mortality, while current therapies for patients exposed lethal doses are limited. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promise tissue repair and regeneration but not been well investigated mitigating damage. We previously demonstrated that human or murine MSC-EVs can reverse bone marrow injury caused by mild moderate radiation. The study evaluated the therapeutic potential of mice total body irradiation (TBI). Mice were 0, 700, 950 cGy TBI subsequently received daily intravenous MSC-EV injections (1 × 109 particles) 3 days postirradiation. survival rates, peripheral blood recovery, engraftment, gene expression profiles at various intervals following treatment. administration significantly enhanced survival, with 70% treated surviving 120 after exposure, compared 0% untreated controls day 30. Although recovery was observed within 14 days, treatment facilitated substantial months postirradiation, significant increases red cell, platelet, white hemoglobin levels, despite cell levels remaining slightly below normal. Furthermore, engraftment capacity cells improved. changes hematopoietic-related presented postirradiation returned normal MSC-EV-treated mice. These highlight as a strategy injuries promoting improving survival. Our future research will focus on elucidating radioprotective mechanisms investigating their integration existing therapies.

Language: Английский

Citations

1
Photo-crosslinked hyaluronic acid hydrogels designed for simultaneous delivery of mesenchymal stem cells and tannic acid: Advancing towards scarless wound healing DOI
Mozhgan Abedanzadeh, Samira Sadat Abolmaali, Reza Heidari

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 281, P. 136394 - 136394

Published: Oct. 13, 2024

Language: Английский

Citations

4
Multi-Omics Sequencing Dissects the Atlas of Seminal Plasma Exosomes from Semen Containing Low or High Rates of Sperm with Cytoplasmic Droplets DOI Open Access

Zilu Zhang,

Xiaoxian Xu,

Fumei Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1096 - 1096

Published: Jan. 27, 2025

Sperm cytoplasmic droplets (CDs) are remnants of cytoplasm that can cause a number problems if it not shed from the sperm after ejaculation. Exosomes rapidly bind to sperm, but is clear whether exosomes affect migration and shedding CDs. We first extracted characterized seminal plasma boar semen containing with low or high rates Then, transcriptomic proteomic detection these were performed analyze differences between two groups exosomes. The results revealed 486 differentially expressed genes (DEGs), 40 proteins (DEPs), 503 lncRNAs (DElncRNAs) identified CD rate group group. Integrative multi-omics analysis showed exosome components may by influencing cytoskeletal regulation insulin signaling, including actin cytoskeleton, ECM–receptor interaction, axon guidance, secretion, signaling pathway. Overall, our study systematically DEGs, DEPs, DElncRNAs in semen, which will help broaden understanding complex molecular mechanisms involved

Language: Английский

Citations

0
Optogenetic activation of mechanical nociceptions to enhance implant osseointegration DOI Creative Commons
Q. Wang, Yang Chen,

Haiqi Ding

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 31, 2025

Orthopedic implants with high elastic modulus often suffer from poor osseointegration due to stress shielding, a phenomenon that suppresses the expression of intracellular mechanotransduction molecules (IMM) such as focal adhesion kinase (FAK). We find reduced FAK under shielding is also mediated by decreased calcitonin gene-related peptide (CGRP) released Piezo2+ mechanosensitive nerves surrounding implant. To activate these minimally invasively, we develop fully implantable, wirelessly rechargeable optogenetic device. In mice engineered express light-sensitive channels in neurons, targeted stimulation L2-3 dorsal root ganglia (DRG) enhances localized CGRP release near This elevation activates Protein Kinase A (PKA)/FAK signaling pathway bone marrow mesenchymal stem cells (BMSCs), thereby enhancing osteogenesis and improving osseointegration. Here show bioelectronic modulation offers strategy address implant failure, bridging neuroregulation bioengineering. Stress common cause orthopedic reduces activity molecules, which are regulated nociceptors. Here, Wang et al. small, device for regulation nociceptors investigate improve

Language: Английский

Citations

0
Engineering cell-derived extracellular matrix for peripheral nerve regeneration DOI Creative Commons
Yingxi Xu, Xianbo Liu, Muhammad Arslan Ahmad

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 27, P. 101125 - 101125

Published: June 13, 2024

Extracellular matrices (ECMs) play a key role in nerve repair and are recognized as the natural source of biomaterials. In parallel to extensively studied tissue-derived ECMs (ts-ECMs), cell-derived (cd-ECMs) also have capability partially recapitulate complicated regenerative microenvironment native tissues. Notably, cd-ECMs can avoid shortcomings ts-ECMs. Cd-ECMs be prepared by culturing various cells or even autologous vitro under pathogen-free conditions. And mild decellularization achieve efficient removal immunogenic components cd-ECMs. Moreover, more readily customizable desired functional properties. These advantages garnered significant attention for potential neuroregenerative medicine. As promising biomaterials, bring new hope effective treatment peripheral injuries. Herein, this review comprehensively examines current knowledge about characteristics their mechanisms interaction with regeneration, particular focus on preparation, engineering optimization, scalability The applications from distinct cell sources reported tissue highlighted summarized. Furthermore, limitations that should addressed outlooks related clinical translation put forward well.

Language: Английский

Citations

3
Comparative Analysis of Serum and Serum-Free Medium Cultured Mesenchymal Stromal Cells for Cartilage Repair DOI Open Access

Meiqi Kang,

Yanmeng Yang, Haifeng Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10627 - 10627

Published: Oct. 2, 2024

Mesenchymal stromal cells (MSCs) are promising candidates for cartilage repair therapy due to their self-renewal, chondrogenic, and immunomodulatory capacities. It is widely recognized that a shift from fetal bovine serum (FBS)-containing medium toward fully chemically defined serum-free (SF) would be necessary clinical applications of MSCs eliminate issues such as xeno-contamination batch-to-batch variation. However, there notable gap in the literature regarding evaluation chondrogenic ability SF-expanded (SF-MSCs). In this study, we compared vivo regeneration effect FBS-MSCs SF-MSCs rat osteochondral defect model found poor outcomes SF-MSCs. Consequently, comparative analysis expanded using two SF media, MesenCult™-ACF (ACF), Custom StemPro™ MSC SFM XenoFree (XF) was conducted vitro. Our results show constitute variations morphology, surface markers, senescence status, differentiation capacity, senescence/apoptosis status. Highly proliferative supported by do not always correlate ability. Prior determination medium’s support therefore crucial when choosing an manufacture application repair.

Language: Английский

Citations

3
3D patterns in alginate hydrogel degradation spatially guide YAP nuclear translocation and hMSC osteogenic differentiation DOI Open Access
Claudia A. Garrido, Daniela S. Garske, Christian H. Bucher

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 15, 2024

Abstract Tissue engineering involves assembling cells and mimicking the complex anisotropic architecture of biological tissues to perform specific functions. This study explores impact patterned hydrogels with degradation compared single-phase materials on potential enhancing cell spreading, collective alignment, mechanotransduction osteogenic differentiation encapsulated human mesenchymal stromal (hMSCs). Spatial patterns degradable (Deg) non-degradable (noDeg) subregions are formed by photolithography: UV-triggered thiol-ene crosslinking matrix metalloprotease (MMP) sensitive peptides form Deg phases, while non-UV exposed regions result in Diels-Alder spontaneous click noDeg phases. 3D hydrogel enhance hMSC spreading allow alignment areas, remain rounded no regions. In addition, we observe a boosted when materials, as mid markers (osteocalcin) expressed at day 14 gels, whereas only early found (osterix). Mechanosensing pathways were evaluated using expression localization YAP. sections have an enhanced nuclear translocation higher YAP sections. effect is lost emerge MMP-scramble peptide or no-RGD materials. These findings demonstrate that alginate guide differentiation. Mimicking tissue anisotropy could broad applications biofabrication engineering. Statement significance Patterned integrate multiple characteristics within single material, closely tissues. research goes further demonstrating how cell-laden leads emerging mechanics. As consequence, morphology shown counterparts. Additionally, show spatially guided Furthermore, mechanosensing via YAP/TAZ signaling mediate this Finally, explore additional biochemical stimuli can boost advance our understanding response microenvironments, Figure 0: Graphical abstract

Language: Английский

Citations

2
Characterization of open chromatin sensitive to actin polymerization and identification of core‐binding factor subunit beta as mechanosensitive nucleocytoplasmic shuttling protein DOI
Yaxin Li,

Kangjing Li,

Fumihiko Nakamura

et al.

Cytoskeleton, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract Mechanotransduction leads to a variety of biological responses including gene expression, changes in cell shape, migration, tissue development, and immune responses. Dysregulation mechanotransduction is implicated the progression various diseases such as cardiovascular cancer. The actin cytoskeleton plays crucial role transmitting mechanical stimuli. Actin filaments, essential for motility shape changes, respond cues by remodeling, influencing expression via linker nucleoskeleton complex mechanosensitive transcription factors. This study employs dithiobis(succinimidyl propionate) (DSP)‐micrococcal nuclease (MNase) proteogenomics method explore relationship between cellular mechanosensing, chromatin architecture, identification proteins involved nucleocytoplasmic shuttling, revealing how polymerization affects expression. We found that depolymerization filaments latrunculin B (Lat B) 30 min sufficient alter open identified core‐binding factor subunit beta shuttling protein.

Language: Английский

Citations

1
Activin A inhibits the migration of human lung adenocarcinoma A549 cells induced by EGF DOI
Fenglin Zhang, Xueling Cui,

Ke Yang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113170 - 113170

Published: Sept. 16, 2024

Language: Английский

Citations

1
Detecting global and local hierarchical structures in cell-cell communication using CrossChat DOI Creative Commons
Xinyi Wang, Axel A. Almet, Qing Nie

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 3, 2024

Abstract Cell-cell communication (CCC) occurs across different biological scales, ranging from interactions between large groups of cells to individual cells, forming a hierarchical structure. Globally, CCC may exist clusters or only subgroups cluster with varying size, while locally, group as sender receiver exhibit distinct signaling properties. Current existing methods infer single-cell RNA-seq Spatial Transcriptomics predefined cell groups, neglecting the structure within that are determined by molecules, in particular, ligands and receptors. Here, we develop CrossChat, novel computational framework designed analyze cell-cell structures using two complementary approaches: global multi-resolution clustering method, multiple local tree detection method. This provides comprehensive approach understand relationships govern complex tissue functions. By applying our method nonspatial scRNA-seq datasets sampled COVID-19 patients mouse embryonic skin, spatial transcriptomics generated Stereo-seq embryo 10x Visium wounded showcase CrossChat’s functionalities for analyzing both communication.

Language: Английский

Citations

1