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1.
Cell Stem Cell ; 31(5): 772-787.e11, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565140

RESUMO

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.


Assuntos
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/fisiologia
2.
Adv Mater ; : e2400346, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594598

RESUMO

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.

3.
Inorg Chem ; 63(10): 4747-4757, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38412230

RESUMO

Low dimensional organic inorganic metal halide materials have shown broadband emission and large Stokes shift, making them widely used in various fields and a promising candidate material. Here, the zero-dimensional lead-free bromide single crystals (C6H14N)3Bi2Br9·H2O (1) and (C6H14N)3Sb3Br12 (2) were synthesized. They crystallized in the monoclinic crystal system with the space group of P21 and P21/n, respectively. Through ultraviolet-visible-near-infrared (UV-vis-NIR) absorption analysis, the band gaps of (C6H14N)3Bi2Br9·H2O and (C6H14N)3Sb3Br12 are found to be 2.75 and 2.83 eV, respectively. Upon photoexcitation, (C6H14N)3Bi2Br9·H2O exhibit broad-band red emission peaking at 640 nm with a large Stokes shift of 180 nm and a lifetime of 2.94 ns, and the emission spectrum of (C6H14N)3Sb3Br12 are similar to those of (C6H14N)3Bi2Br9·H2O. This exclusive red emission is ascribed to the self-trapping exciton transition caused by lattice distortion, which is confirmed through both experiments and first-principles calculations. In addition, due to the polar space group structure and the large spin-orbit coupling (SOC) associated with the heavy elements of Bi and Br of crystal 1, an obvious Rashba effect was observed. The discovery of organic inorganic metal bromide material provides a critical foundation for uncovering the connection between 0D metal halide materials' structures and properties.

4.
J Am Chem Soc ; 146(2): 1491-1500, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38170908

RESUMO

3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).

5.
J Am Chem Soc ; 145(50): 27690-27701, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38069810

RESUMO

The porous coordination cage PCC-1 represents a new platform potentially useful for the cellular delivery of drugs with poor cell permeability and solubility. PCC-1 is a metal-organic polyhedron constructed from zinc metal ions and organic ligands through coordination bonds. PCC-1 possesses an internal cavity that is suitable for drug encapsulation. To better understand the biocompatibility of PCC-1 with human cells, the cell entry mechanism, disassembly, and toxicity of the nanocage were investigated. PCC-1 localizes in the nuclei and cytoplasm within minutes upon incubation with cells, independent of endocytosis and cargo, suggesting direct plasma membrane translocation of the nanocage carrying its guest in its internal cavity. Furthermore, the rates of cell entry correlate to extracellular concentrations, indicating that PCC-1 is likely diffusing passively through the membrane despite its relatively large size. Once inside cells, PCC-1 disintegrates into zinc metal ions and ligands over a period of several hours, each component being cleared from cells within 1 day. PCC-1 is relatively safe for cells at low micromolar concentrations but becomes inhibitory to cell proliferation and toxic above a concentration or incubation time threshold. However, cells surviving these conditions can return to homeostasis 3-5 days after exposure. Overall, these findings demonstrate that PCC-1 enters live cells by crossing biological membranes spontaneously. This should prove useful to deliver drugs that lack this capacity on their own, provided that the dosage and exposure time are controlled to avoid toxicity.


Assuntos
Sistemas de Liberação de Medicamentos , Internalização do Vírus , Humanos , Membrana Celular/metabolismo , Metais/metabolismo , Compostos Orgânicos/metabolismo , Zinco/metabolismo , Íons/metabolismo
6.
ACS Nano ; 17(24): 25591-25613, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38078771

RESUMO

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.


Assuntos
Remielinização , Traumatismos da Medula Espinal , Ratos , Animais , Axônios , Regeneração Nervosa , Medula Espinal , Traumatismos da Medula Espinal/terapia
7.
Gut Microbes ; 15(2): 2284247, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38057970

RESUMO

The occurrence and development of Parkinson's disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1-3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [-12.98, -0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Humanos , Transplante de Microbiota Fecal/métodos , Doença de Parkinson/terapia , Disbiose/terapia , Disbiose/etiologia , China , Resultado do Tratamento , Fezes
8.
Artigo em Inglês | MEDLINE | ID: mdl-37971467

RESUMO

Objective: To investigate the protective effect of Illicium verum extract on the vascularization of osteoporotic fracture in rats, and to elucidate its potential mechanism. Methods: The osteoporotic fracture model was established in ovariectomized rats. Rats were infused with 0.05 ml/kg extract in the stomach every morning. Eighteen rats are then divided into control group, model group, and Illicium verum extract group with 6 rats in each group. To observe the therapeutic effect of Illicium verum extract on osteoporotic rats. Femoral bone mineral density and elastic segment end-point load were evaluated by dual-energy x-ray absorptiometry and three-point bending test. Hematoxylin-eosin staining was used to measure the number and area of callus blood vessels. The serum levels of VEGF and NO were detected by ELISA. Moreover, the expressions of NOX2, NOX4, NRF2, p-PI3K, CyclinD1, VEGF, HIF1α, and eNOS in HUVEC were detected by Western blot. CCK8 and wound healing assay were used to detect the proliferation and migration of HUVEC. Then, the ability of HUVEC to form blood vessels was detected by tube formation assay. Results: Firstly, control group showed the normal pathomorphology and density of femoral bone, and model group showed significantly decreased bone density and consistent with bone microstructure degeneration, destruction, thinning, and fracture of bone trabecular structure vs control group, and illicium verum extract significantly increased femoral density and maximum load, increased the number and area of callus blood vessels and increased VEGF and NO levels in serum vs model group. Then, Illicium verum extract promoted the expression of NRF2, p-PI3K, CyclinD1, VEGF, HIF1α, and eNOS protein in HUVEC, inhibited the expression of NOX2 and NOX4, and enhanced the cell proliferation, migration, and angiogenesis. However, the effect was reversed by the overexpression of NRF2 and the treatment with LY294002. Conclusion: Illicium verum extract protects the vascularization of the osteoporotic fracture model in rats.

9.
Nat Commun ; 14(1): 4796, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558705

RESUMO

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.


Assuntos
Traumatismos da Medula Espinal , Medula Espinal , Animais , Feminino , Macaca mulatta , Medula Espinal/patologia , Neuroglia/patologia , Análise de Célula Única
10.
iScience ; 26(6): 106850, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37275526

RESUMO

Syringomyelia is a common clinical lesion associated with cerebrospinal fluid flow abnormalities. By a reversible model with chronic extradural compression to mimic human canalicular syringomyelia, we explored the spatiotemporal pathological alterations during syrinx development. The most dynamic alterations were observed in ependymal cells (EPCs), oligodendrocyte lineage, and microglia, as a response to neuroinflammation. Among different cell types, EPC subtypes experienced obvious dynamic alterations, which were accompanied by ultrastructural changes involving the ependymal cytoskeleton, cilia, and dynamic injury in parenchyma primarily around the central canal, corresponding to the single-cell transcripts. After effective decompression, the syrinx resolved with the recovery of pathological damage and overall neurological function, implying that for syringomyelia in the early stage, there was still endogenous repair potential coexisting with immune microenvironment imbalance. Ependymal remodeling and cilia restoration might be important for better resolution of syringomyelia and parenchymal injury recovery.

11.
Int J Cardiol ; 387: 131107, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37271285

RESUMO

The three major techniques for clinically diagnosing coronary heart disease, including angina associated with myocardial ischemia, are coronary angiography, myocardial perfusion imaging, and drug stress echocardiography. Compared to the first two methods, which are invasive or involve the use of radionuclides, drug stress echocardiography is increasingly used in clinical practice due to its non-invasive, low-risk, and controllable nature, and wide applicability. We developed a novel methodology to demonstrate knowledge graph-based efficacy analysis of drug stress echocardiography as a complement to traditional meta-analysis. By measuring coronary flow reserve (CFR), we discovered that regional ventricular wall abnormalities (RVWA) and drug-loaded cardiac ultrasound can be used to detect coronary artery disease. Additionally, drug-loaded cardiac ultrasound can be used to identify areas of cardiac ischemia, stratify risks, and determine prognosis. Furthermore, adenosine stress echocardiography(ASE) can determine atypical symptoms of coronary heart disease with associated cardiac events through CFR and related quantitative indices for risk stratification. Using a knowledge graph-based approach, we investigated the positive and negative effects of three drugs - Dipyridamole, Dobutamine, and Adenosine - for coronary artery disease analysis. Our findings show that Adenosine has the highest positive effect and the lowest negative effect among the three drugs. Due to its minimal and controlled side effects, and high sensitivity for diagnosing coronary microcirculation disorders and multiple lesions, adenosine is frequently used in clinical practice.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia sob Estresse/métodos , Prognóstico , Reconhecimento Automatizado de Padrão , Isquemia Miocárdica/diagnóstico por imagem , Adenosina , Dipiridamol , Dobutamina , Medição de Risco
12.
Front Microbiol ; 14: 1188455, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37389342

RESUMO

Pharmacological treatment of inflammatory bowel disease (IBD) is inefficient and difficult to discontinue appropriately, and enterobacterial interactions are expected to provide a new target for the treatment of IBD. We collected recent studies on the enterobacterial interactions among the host, enterobacteria, and their metabolite products and discuss potential therapeutic options. Intestinal flora interactions in IBD are affected in the reduced bacterial diversity, impact the immune system and are influenced by multiple factors such as host genetics and diet. Enterobacterial metabolites such as SCFAs, bile acids, and tryptophan also play important roles in enterobacterial interactions, especially in the progression of IBD. Therapeutically, a wide range of sources of probiotics and prebiotics exhibit potential therapeutic benefit in IBD through enterobacterial interactions, and some have gained wide recognition as adjuvant drugs. Different dietary patterns and foods, especially functional foods, are novel therapeutic modalities that distinguish pro-and prebiotics from traditional medications. Combined studies with food science may significantly improve the therapeutic experience of patients with IBD. In this review, we provide a brief overview of the role of enterobacteria and their metabolites in enterobacterial interactions, discuss the advantages and disadvantages of the potential therapeutic options derived from such metabolites, and postulate directions for further research.

13.
Therap Adv Gastroenterol ; 16: 17562848231170945, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251086

RESUMO

Background: The ulcerative colitis (UC) Mayo endoscopy score is a useful tool for evaluating the severity of UC in patients in clinical practice. Objectives: We aimed to develop and validate a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. Design: A multicenter, diagnostic retrospective study. Methods: We collected 15120 colonoscopy images of 768 UC patients from two hospitals in China and developed a deep model based on a vision transformer named the UC-former. The performance of the UC-former was compared with that of six endoscopists on the internal test set. Furthermore, multicenter validation from three hospitals was also carried out to evaluate UC-former's generalization performance. Results: On the internal test set, the areas under the curve of Mayo 0, Mayo 1, Mayo 2, and Mayo 3 achieved by the UC-former were 0.998, 0.984, 0.973, and 0.990, respectively. The accuracy (ACC) achieved by the UC-former was 90.8%, which is higher than that achieved by the best senior endoscopist. For three multicenter external validations, the ACC was 82.4%, 85.0%, and 83.6%, respectively. Conclusions: The developed UC-former could achieve high ACC, fidelity, and stability to evaluate the severity of UC, which may provide potential application in clinical practice. Registration: This clinical trial was registered at the ClinicalTrials.gov (trial registration number: NCT05336773).


Why was this study done? The development of an auxiliary diagnostic tool can reduce the workload of endoscopists and achieve rapid assessment of ulcerative colitis (UC) severity. What did the researchers do? We developed and validated a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. What did the researchers find? The model that was developed in this study achieved high accuracy, fidelity, and stability, and demonstrated potential application in clinical practice. What do the findings mean? Deep learning could effectively assist endoscopists in evaluating the severity of UC in patients using endoscopic images.

14.
Bioact Mater ; 27: 125-137, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37064803

RESUMO

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

15.
Inorg Chem ; 62(10): 4314-4321, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36857778

RESUMO

A new fluoro-bridged rare-earth (RE) metal-organic framework consisting of 15-connected nonanuclear and 9-connected trinuclear clusters {[RE9-(µ3-F)14(H2O)6][RE3(µ3-F)(H2O)3](HCO2)3-(BTB)6}·(solvent)x 2 (RE = Ho3+ and Gd3+) was synthesized through the transformation of a dimeric complex formulated as bis(2,2'-bipyridine)tetrakis(µ-2-fluorobenzoato-O,O')-bis(2-fluorobenzoato)diRE(III) 1 with the bridging linker 1,3,5-tris(4-carboxyphenyl)benzene (H3BTB). The rare-earth metal ions Ho3+ and Gd3+ were also found to remove fluorine from other organo-fluorine compounds such as perfluorohexanoic acid (PFHxA) and perfluorooctanoic acid (PFOA), resulting in the new fluoro-bridged RE-MOFs.

16.
Cell Prolif ; 56(5): e13451, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36916024

RESUMO

The strategy of replacing a completely damaged spinal cord with allogenic adult spinal cord tissues (aSCs) can potentially repair complete spinal cord injury (SCI) in combination with immunosuppressive drugs, such as tacrolimus (Tac), which suppress transplant rejection and improve graft survival. However, daily systemic administration of immunosuppressive agents may cause harsh side effects. Herein, a localized, sustained Tac-release collagen hydrogel (Col/Tac) was developed to maximize the immune regulatory efficacy but minimize the side effects of Tac after aSC transplantation in complete SCI recipients. Thoracic aSCs of rat donors were transplanted into the complete thoracic spinal cord transection rat recipients, after which Col/Tac hydrogel was implanted. The Tac-encapsulated collagen hydrogel exhibited suitable mechanical properties and long-term sustained Tac release behaviour. After Col/Tac hydrogel implantation in SCI rats with aSC transplantation, the recipients' survival rate significantly improved and the side effects on tissues were reduced compared with those with conventional Tac medication. Moreover, treatment with the Col/Tac hydrogel exhibited similarly reduced immune rejection levels by regulating immune responses and promoted neurogenesis compared to daily Tac injections, and thus improved functional restoration. Localized delivery of immunosuppressive agents by the Col/Tac hydrogel may be a promising strategy for overcoming immune rejection of transplants, with significant potential for clinical application in the future.


Assuntos
Traumatismos da Medula Espinal , Tacrolimo , Ratos , Animais , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Hidrogéis/farmacologia , Preparações de Ação Retardada/farmacologia , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Colágeno
17.
Dalton Trans ; 52(14): 4415-4422, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36916445

RESUMO

A new mixed linker metal-organic framework (MOF) has been synthesized from a copper-based metal-organic polyhedron (MOP-1) and 2,2'-bipyridine (2,2'-bipy). The CuMOF-Bipy with a formula of [Cu2(2,2'-bpy)2(m-BDC)2]n is comprised of a binuclear Cu(II) node coordinated to 2,2'-bipy, and isophthalic acid (m-BDC), which bridges to neighboring nodes. The crystal structure of CuMOF-Bipy consists of a stacked two-dimensional framework with the sql topology. CuMOF-Bipy was characterized by single-crystal X-ray diffraction (SC-XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and CO2 sorption. CuMOF-Bipy was shown to have one-dimensional sinusoidal channels that allow diffusion of CO2 but not N2.

18.
Bioeng Transl Med ; 8(2): e10448, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925694

RESUMO

Neural progenitor cell (NPC) transplantation is a promising approach for repairing spinal cord injury (SCI). However, cell survival, maturation and integration after transplantation are still major challenges. Here, we produced a novel centimeter-scale human spinal cord neural tissue (hscNT) construct with human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, to form a linearly ordered spinal cord-like structure consisting of mature neurons and glia cells. When transplanted into rats with SCI, the hscNT created a favorable microenvironment by inhibiting inflammation and glial scar formation, and promoted neural and vascular regeneration. Notably, the hscNT promoted neural circuit reconstruction and motor functional recovery. Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may therefore have potential in the treatment of SCI.

19.
Sci Adv ; 9(6): eade8829, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36753555

RESUMO

Noncovalent interactions between cells and environmental cues have been recognized as fundamental physiological interactions that regulate cell behavior. However, the effects of the covalent interactions between cells and biomaterials on cell behavior have not been examined. Here, we demonstrate a combined strategy based on covalent conjugation between biomaterials (collagen fibers/lipid nanoparticles) and various cells (exogenous neural progenitor cells/astrocytes/endogenous tissue-resident cells) to promote neural regeneration after spinal cord injury (SCI). We found that metabolic azido-labeled human neural progenitor cells conjugated on dibenzocyclooctyne-modified collagen fibers significantly promoted cell adhesion, spreading, and differentiation compared with noncovalent adhesion. In addition, dibenzocyclooctyne-modified lipid nanoparticles containing edaravone, a well-known ROS scavenger, could target azide-labeled spinal cord tissues or transplanted azide-modified astrocytes to improve the SCI microenvironment. The combined application of these covalent conjugation strategies in a rat SCI model boosted neural regeneration, suggesting that the covalent interactions between cells and biomaterials have great potential for tissue regeneration.


Assuntos
Materiais Biocompatíveis , Traumatismos da Medula Espinal , Ratos , Animais , Humanos , Materiais Biocompatíveis/farmacologia , Engenharia Tecidual , Alicerces Teciduais , Azidas , Medula Espinal , Traumatismos da Medula Espinal/terapia , Colágeno
20.
Bioact Mater ; 23: 300-313, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36439085

RESUMO

Neural stem progenitor cell (NSPC) transplantation has been regarded as a promising therapeutic method for spinal cord injury (SCI) repair. However, different NSPCs may have different therapeutic effects, and it is therefore important to identify the optimal NSPC type. In our study, we compared the transcriptomes of human fetal brain-derived NSPCs (BNSPCs), spinal cord-derived NSPCs (SCNSPCs) and H9 embryonic stem-cell derived NSPCs (H9-NSPCs) in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo. In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types. In vivo, compared with BNSPCs and H9-NSPCs, SCNSPCs exhibited the best therapeutic effects; in fact, SCNSPCs facilitated electrophysiological and hindlimb functional recovery. This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair, which is of great clinical significance.

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