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The development of engineered or modified autologous stem cells is an effective strategy to improve the efficacy of stem cell therapy. In this study, the stemness and functionality of adipose stem cells derived from type 1 diabetic donors (T1DM-ASC) were enhanced by treatment with Cu(II)-baicalein microflowers (Cu-MON). After treatment with Cu-MON, T1DM-ASC showed enhanced expression of the genes involved in the cytokine-cytokine receptor interaction pathway and increased cytokine secretion. Among the top 13 differentially expressed genes between T1DM-ASC and Cu-MON-treated T1DM-ASC (CMTA), some genes were also expressed in HUVEC, Myoblast, Myofibroblast, and Vascular Smooth Muscle cells, inferring the common role of these cell types. In vivo experiments showed that CMTA had the same therapeutic effect as adipose-derived stem cells from non-diabetic donors (ND-ASC) at a 15% cell dose, greatly reducing the treatment cost. Taken together, these findings suggest that Cu-MON promoted angiogenesis by promoting the stemness and functionality of T1DM-ASC and influencing multiple overall repair processes, including paracrine effects.
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Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.
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Cicatriz , Fibroblastos , Fibrose , Laminina , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Cicatriz/patologia , Cicatriz/metabolismo , Camundongos , Feminino , Laminina/metabolismo , Meninges/patologia , Meninges/metabolismo , Fibronectinas/metabolismo , Modelos Animais de Doenças , Colágeno Tipo I/metabolismo , Camundongos Endogâmicos C57BL , Pericitos/metabolismo , Pericitos/patologia , Colágeno Tipo IV/metabolismo , Colesterol/metabolismoRESUMO
Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.
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Proteínas de Transporte , Citocinas , Matriz Extracelular , Organoides , Traumatismos da Medula Espinal , Medula Espinal , Animais , Organoides/metabolismo , Organoides/citologia , Medula Espinal/metabolismo , Matriz Extracelular/metabolismo , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Coelhos , Diferenciação Celular , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Tenascina/metabolismo , Proliferação de Células , Animais Recém-Nascidos , Regeneração Nervosa/fisiologiaRESUMO
Spinal cord injury (SCI) is a devastating neurological disorder, leading to loss of motor or somatosensory function, which is the most challenging worldwide medical problem. Re-establishment of intact neural circuits is the basis of spinal cord regeneration. Considering the crucial role of electrical signals in the nervous system, electroactive bioscaffolds have been widely developed for SCI repair. They can produce conductive pathways and a pro-regenerative microenvironment at the lesion site similar to that of the natural spinal cord, leading to neuronal regeneration and axonal growth, and functionally reactivating the damaged neural circuits. In this review, we first demonstrate the pathophysiological characteristics induced by SCI. Then, the crucial role of electrical signals in SCI repair is introduced. Based on a comprehensive analysis of these characteristics, recent advances in the electroactive bioscaffolds for SCI repair are summarized, focusing on both the conductive bioscaffolds and piezoelectric bioscaffolds, used independently or in combination with external electronic stimulation. Finally, thoughts on challenges and opportunities that may shape the future of bioscaffolds in SCI repair are concluded.
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Traumatismos da Medula Espinal , Alicerces Teciduais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Humanos , Animais , Regeneração Nervosa , Axônios/fisiologia , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Medula Espinal , Condutividade Elétrica , Regeneração da Medula Espinal , Estimulação Elétrica/métodosRESUMO
Bioelectricity plays a crucial role in organisms, being closely connected to neural activity and physiological processes. Disruptions in the nervous system can lead to chaotic ionic currents at the injured site, causing disturbances in the local cellular microenvironment, impairing biological pathways, and resulting in a loss of neural functions. Electromagnetic stimulation has the ability to generate internal currents, which can be utilized to counter tissue damage and aid in the restoration of movement in paralyzed limbs. By incorporating implanted materials, electromagnetic stimulation can be targeted more accurately, thereby significantly improving the effectiveness and safety of such interventions. Currently, there have been significant advancements in the development of numerous promising electromagnetic stimulation strategies with diverse materials. This review provides a comprehensive summary of the fundamental theories, neural stimulation modulating materials, material application strategies, and pre-clinical therapeutic effects associated with electromagnetic stimulation for neural repair. It offers a thorough analysis of current techniques that employ materials to enhance electromagnetic stimulation, as well as potential therapeutic strategies for future applications.
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Materiais Biocompatíveis , Humanos , Animais , Materiais Biocompatíveis/química , Terapia por Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/instrumentaçãoRESUMO
Essential oils (EOs) are liquid extracts derived from various parts of herbal or medicinal plants. They are widely accepted in food packaging due to their bioactive components, which exhibit remarkable antioxidant and antimicrobial properties against various pathogenic and food spoilage microorganisms. However, the functional efficacy of EOs is hindered by the high volatility of their bioactive compounds, leading to rapid release. Combining biopolymers with EOs forms a complex network within the polymeric matrix, reducing the volatility of EOs, controlling their release, and enhancing thermal and mechanical stability, favoring their application in food packaging or processing industries. This study presents a comprehensive overview of techniques used to encapsulate EOs, the natural polymers employed to load EOs, and the functional properties of EOs-loaded biopolymeric particles, along with their potential antioxidant and antimicrobial benefits. Additionally, a thorough discussion is provided on the widespread application of EOs-loaded biopolymers in the food industries. However, research on their utilization in confectionery processing, such as biscuits, chocolates, and others, remains limited. Further studies can be conducted to explore and expand the applications of EOs-loaded biopolymeric particles in food processing industries.
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Anti-Infecciosos , Óleos Voláteis , Óleos Voláteis/farmacologia , Antioxidantes/farmacologia , Indústria de Processamento de Alimentos , Embalagem de Alimentos/métodos , Biopolímeros , Polímeros , Indústria AlimentíciaRESUMO
Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered spinal cord tissues that can replenish lost cells and restore a regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human spinal cord-like tissues (VSCT) that mimic the diverse cell types and longitudinal parallel structural features of spinal cord tissues remains a significant hurdle. In the present study, VSCTs are engineered using embryonic human spinal cord-derived neural and endothelial cells on linear-ordered collagen scaffolds (LOCS). Studies have shown that astrocytes and endothelial cells align along the scaffolds in VSCT, supporting axon extension from various human neurons myelinated by oligodendrocytes. After transplantation into SCI rats, VSCT survives at the injury sites and promotes endogenous neural regeneration and vascularization, ultimately reducing scarring and enhancing behavioral functional recovery. It suggests that pre-vascularization of engineered spinal cord tissues is beneficial for SCI treatment and highlights the important role of exogenous endothelial cells in tissue engineering.
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Traumatismos da Medula Espinal , Medula Espinal , Engenharia Tecidual , Alicerces Teciduais , Traumatismos da Medula Espinal/terapia , Humanos , Animais , Engenharia Tecidual/métodos , Ratos , Alicerces Teciduais/química , Ratos Sprague-Dawley , Células Endoteliais/citologia , Regeneração Nervosa/fisiologia , Neovascularização Fisiológica , Colágeno/química , FemininoRESUMO
Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.
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Colágeno , Mecanotransdução Celular , Células-Tronco Neurais , Proteínas Proto-Oncogênicas c-akt , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Animais , Porosidade , Células-Tronco Neurais/metabolismo , Colágeno/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Nicho de Células-Tronco , Biomimética , Diferenciação Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alicerces Teciduais/química , Materiais Biomiméticos/química , Proteínas de Sinalização YAPRESUMO
Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural stem cells (NSCs), thereby effectively providing a source of transplanted cells for spinal cord injury (SCI). To further improve the repair efficiency of SCI, we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation of this tissue regenerated neurons and synapses, improved the microenvironment of the injured area, enhanced remodeling of the extracellular matrix, and promoted functional recovery of the hind limbs in a rat SCI model with complete transection. RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI. Together, we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time. This tissue can effectively improve the therapeutic effect of SCI, thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.
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In women, a healthy and functional vagina is important for the maintenance of a good quality of life. Various factors, including congenital anomalies, cancer, trauma, infections, inflammation, or iatrogenic injuries, can lead to damage or loss of the vaginal structure, necessitating repair or replacement. Often, such reconstruction procedures involve the use of nonvaginal tissue substitutes, like segments of the large intestine or skin, which are less than ideal both anatomically and functionally. Therefore, there is an urgent need to develop new methods of vaginal reconstruction. In this study, we established a new method for isolation and expansion of vaginal epithelial and smooth muscle cells. Subsequently, collagen scaffolds designed for vaginal reconstruction were loaded with vaginal epithelial and smooth muscle cells in vitro and tested in vivo using the vaginal excision pig model. The results showed that the collagen scaffold loaded with vaginal epithelial and smooth muscle cells significantly promotes the reconstruction of the vagina compared with small intestinal submucosa (SIS) membrane or bare collagen scaffold. Notably, the reconstructed vaginal tissues exhibit remarkable similarity to their normal counterparts, encompassing not only the vaginal epithelium and smooth muscle but also the intricate networks of blood vessels and nerves. These compelling results underscore the feasibility of a tissue engineering approach in vaginal reconstruction, offering promising prospects for improving the quality of life in affected individuals.
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Qualidade de Vida , Vagina , Feminino , Humanos , Animais , Suínos , Vagina/cirurgia , Miócitos de Músculo Liso , Colágeno , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
Intrauterine adhesion is a major cause of female reproductive disorders. Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth, no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far. To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate, we conducted this randomized controlled clinical trial. Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter (control group) from February 2016 to January 2020. The per-protocol analysis included 140 participants: 72 in bone marrow stem cells-scaffold group and 68 in control group. The ongoing pregnancy occurred in 45/72 (62.5%) participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group (28/68, 41.2%) (RR=1.52, 95%CI 1.08-2.12, P=0.012). The situation was similar in live birth rate (bone marrow stem cells-scaffold group 56.9% (41/72) vs. control group 38.2% (26/68), RR=1.49, 95%CI 1.04-2.14, P=0.027). Compared with control group, participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis. The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed. In conclusion, transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates, and this therapy was relatively safe.
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Doenças Uterinas , Feminino , Humanos , Gravidez , Células da Medula Óssea , Endométrio , Taxa de Gravidez , Aderências Teciduais , ÚteroRESUMO
Spinal cord injury (SCI) causes tissue structure damage and composition changes of the neural parenchyma, resulting in severe consequences for spinal cord function. Mimicking the components and microstructure of spinal cord tissues holds promise for restoring the regenerative microenvironment after SCI. Here, we have utilized electrospinning technology to develop aligned decellularized spinal cord fibers (A-DSCF) without requiring synthetic polymers or organic solvents. A-DSCF preserves multiple types of spinal cord extracellular matrix proteins and forms a parallel-oriented structure. Compared to aligned collagen fibers (A-CF), A-DSCF exhibits stronger mechanical properties, improved enzymatic stability, and superior functionality in the adhesion, proliferation, axonal extension, and myelination of differentiated neural progenitor cells (NPCs). Notably, axon extension or myelination has been primarily linked to Agrin (AGRN), Laminin (LN), or Collagen type IV (COL IV) proteins in A-DSCF. When transplanted into rats with complete SCI, A-DSCF loaded with NPCs improves the survival, maturation, axon regeneration, and motor function of the SCI rats. These findings highlight the potential of structurally and compositionally biomimetic scaffolds to promote axonal extension and remyelination after SCI.
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Remielinização , Traumatismos da Medula Espinal , Ratos , Animais , Axônios , Regeneração Nervosa , Medula Espinal , Traumatismos da Medula Espinal/terapiaRESUMO
Due to adhesion and rejection of recent traditional materials, it is still challenging to promote the regenerative repair of abdominal wall defects caused by different hernias or severe trauma. However, biomaterials with a high biocompatibility and low immunogenicity have exhibited great potential in the regeneration of abdominal muscle tissue. Previously, we have designed a biological collagen scaffold material combined with growth factor, which enables a fusion protein-collagen binding domain (CBD)-basic fibroblast growth factor (bFGF) to bind and release specifically. Though experiments in rodent animals have indicated the regeneration function of CBD-bFGF modified biological collagen scaffolds, its translational properties in large animals or humans are still in need of solid evidence. In this study, the abdominal wall defect model of Bama miniature pigs was established by artificial operations, and the defective abdominal wall was sealed with or without a polypropylene patch, and unmodified and CBD-bFGF modified biological collagen scaffolds. Results showed that a recurrent abdominal hernia was observed in the defect control group (without the use of mesh). Although the polypropylene patch can repair the abdominal wall defect, it also induced serious adhesion and inflammation. Meanwhile, both kinds of collagen biomaterials exhibited positive effects in repairing abdominal wall defects and reducing regional adhesion and inflammation. However, CBD-bFGF-modified collagen biomaterials failed to induce the regenerative repair reported in rat experiments. In addition, unmodified collagen biomaterials induced abdominal wall muscle regeneration rather than fibrotic repair. These results indicated that the unmodified collagen biomaterials are a better option among translational patches for the treatment of abdominal wall defects.
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Parede Abdominal , Materiais Biocompatíveis , Humanos , Ratos , Suínos , Animais , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais/química , Porco Miniatura/metabolismo , Parede Abdominal/cirurgia , Polipropilenos , Colágeno/química , Aderências Teciduais , InflamaçãoRESUMO
Tissue engineering techniques bring the promise of vaginal reconstruction with low invasiveness and fewer complications. However, existing biomaterial scaffolds remain limited in efficient vaginal recovery, focusing only on regenerating an epithelial layer, but muscle layers are missing or abnormal. The lack of a multi-tissue hierarchical structure in the reconstructed vagina leads to shrinking, stenosis, and fibrosis. Here, an acellular matrix named a double-sided biomembrane (DBM) is demonstrated for vaginal recovery. The regeneration of epithelial and muscle layers is achieved simultaneously since the smooth side of the DBM is helpful for guiding epithelial cell growth, while its loose and porous side guides muscle cell growth. In addition, the DBM demonstrates excellent mechanical properties similar to vaginal tissue, and hydrophilicity. Therefore, neovaginas were observed in the fourth and twelfth weeks after DBMs were transplanted to repair full-thickness vaginal defects (4 cm) that we established in large animals. The DBMs can effectively promote rapid epithelialization, the formation of large muscle bundles, higher rates of angiogenesis, and the restoration of physiological function in a neovagina. That is, the injured vagina achieves nearly complete recovery in anatomy and function, similar to a normal vagina. These preclinical results indicate that the DBM has prospects for vaginal injury repair.
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Introduction: Insect pests from the family Papilionidae (IPPs) are a seasonal threat to citrus orchards, causing damage to young leaves, affecting canopy formation and fruiting. Existing pest detection models used by orchard plant protection equipment lack a balance between inference speed and accuracy. Methods: To address this issue, we propose an adaptive spatial feature fusion and lightweight detection model for IPPs, called ASFL-YOLOX. Our model includes several optimizations, such as the use of the Tanh-Softplus activation function, integration of the efficient channel attention mechanism, adoption of the adaptive spatial feature fusion module, and implementation of the soft Dlou non-maximum suppression algorithm. We also propose a structured pruning curation technique to eliminate unnecessary connections and network parameters. Results: Experimental results demonstrate that ASFL-YOLOX outperforms previous models in terms of inference speed and accuracy. Our model shows an increase in inference speed by 29 FPS compared to YOLOv7-x, a higher mAP of approximately 10% than YOLOv7-tiny, and a faster inference frame rate on embedded platforms compared to SSD300 and Faster R-CNN. We compressed the model parameters of ASFL-YOLOX by 88.97%, reducing the number of floating point operations per second from 141.90G to 30.87G while achieving an mAP higher than 95%. Discussion: Our model can accurately and quickly detect fruit tree pest stress in unstructured orchards and is suitable for transplantation to embedded systems. This can provide technical support for pest identification and localization systems for orchard plant protection equipment.
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Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.
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Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, the cellular dynamic responses and heterogeneity across different regions below the lesion remain to be elusive. Here, we used single-cell transcriptomics to investigate the region-related cellular responses in female rhesus monkeys with complete thoracic SCI from acute to chronic phases. We found that distal lumbar tissue cells were severely impacted, leading to degenerative microenvironments characterized by disease-associated microglia and oligodendrocytes activation alongside increased inhibitory interneurons proportion following SCI. By implanting scaffold into the injury sites, we could improve the injury microenvironment through glial cells and fibroblast regulation while remodeling spared lumbar tissues via reduced inhibitory neurons proportion and improved phagocytosis and myelination. Our findings offer crucial pathological insights into the spared distal tissues and proximal tissues after SCI, emphasizing the importance of scaffold-based treatment approaches targeting heterogeneous microenvironments.
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Traumatismos da Medula Espinal , Medula Espinal , Animais , Feminino , Macaca mulatta , Medula Espinal/patologia , Neuroglia/patologia , Análise de Célula ÚnicaRESUMO
Therapeutic options are limited for severe lung injury and disease as the spontaneous regeneration of functional alveolar is terminated owing to the weakness of the inherent stem cells and the dyscrasia of the niche. Umbilical cord mesenchymal-derived stem cells (UC-MSCs) have been applied to clinical trials to promote lung repair through stem cell niche restruction. However, the application of UC-MSCs is hampered by the effectiveness of cell transplantation with few cells homing to the injury sites and poor retention, survival, and proliferation in vivo. In this study, we constructed an artificial three-dimensional (3D) biomimetic scaffold-based MSCs implant to establish a beneficial regeneration niche for endogenous stem cells in situ lung regeneration. The therapeutic potential of 3D biomimetic scaffold-based MSCs implants was evaluated by 3D culture in vitro. And RNA sequencing (RNA-Seq) was mapped to explore the gene expression involved in the niche improvement. Next, a model of partial lung resection was established in rats, and the implants were implanted into the operative region. Effects of the implants on rat resected lung injury repair were detected. The results revealed that UC-MSCs loaded on biomimetic scaffolds exerted strong paracrine effects and some UC-MSCs migrated to the lung from scaffolds and had long-term retention to suppress inflammation and fibrosis in residual lungs and promoted vascular endothelial cells and alveolar type II epithelial cells to enter the scaffolds. Then, under the guidance of the ECM-mimicking structures of scaffolds and the stimulation of the remaining UC-MSCs, vascular and alveolar-like structures were formed in the scaffold region. Moreover, the general morphology of the operative lung was also restored. Taken together, the artificial 3D biomimetic scaffold-based MSCs implants induce in situ lung regeneration and recovery after lung destruction, providing a promising direction for tissue engineering and stem cell strategies in lung regeneration.
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Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301+ macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single-cell RNA sequencing, bulk RNA sequencing, and experimental verification. Increasing CD301+ macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts and resulted in extracellular matrix accumulation, which destroyed the physiological architecture of endometrial tissue, drove endometrial fibrosis, and ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, CD301+ macrophages secreted GAS6 to activate the AXL/NF-κB pathway, upregulating the profibrotic protein synthesis. Targeted deletion of CD301+ macrophages or inhibition of AXL by Bemcentinib blunted the pathology and improved the outcomes of pregnancy in mice, supporting the therapeutic potential of targeting CD301+ macrophages for treating endometrial fibrosis.
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Resultado da Gravidez , Doenças Uterinas , Humanos , Gravidez , Feminino , Camundongos , Animais , Doenças Uterinas/metabolismo , Doenças Uterinas/patologia , Doenças Uterinas/terapia , Endométrio/metabolismo , Endométrio/patologia , Macrófagos/metabolismo , FibroseRESUMO
Controllable drug delivery systems (DDS) can overcome the disadvantages of conventional drug administration processes, such as high dosages or repeated administration. Herein, a smart DDS collagen hydrogel is deployed for spinal cord injury (SCI) repair based on modular designing of "egg" nanoparticles (NPs) that ingeniously accomplish controlled drug release via inducing a signaling cascade in response to external and internal stimuli. The "egg" NPs consist of a three-layered structure: tannic acid/Fe3+ /tetradecanol "eggshell," zeolitic imidazolate framework-8 (ZIF-8) "egg white," and paclitaxel "yolk." Then NPs served as a crosslinking epicenter, blending with collagen solutions to generate functional hydrogels. Remarkably, the "eggshell" efficiently converts near-infrared (NIR) irradiation into heat. Subsequently, tetradecanol can be triggered to disintegrate via heat, exposing the structure of ZIF-8. The Zn-imidazolium ion coordination bond of the "egg white" is susceptible to cleaving at the acidic SCI site, decomposing the skeleton to release paclitaxel on demand. As expected, the paclitaxel release rate upon NIR irradiation increased up to threefold on the seventh day, which matches endogenous neural stem/progenitor cell migration process. Taken together, the collagen hydrogels facilitate the neurogenesis and motor function recovery, demonstrating a revolutionary strategy for spatiotemporally controlled drug release and providing guidelines for the design of DDS.