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Mesenchymal stem cell-loaded hydrogel improves surgical treatment for chronic cerebral ischemia

ABSTRACT: Chronic cerebral ischemia (CCI) results in a prolonged insufficient blood supply to the brain tissue, leading to impaired neuronal function and subsequent impairment of cognitive and motor abilities. Our previous research showed that in mice with bilateral carotid artery stenosis, the collateral neovascularization post Encephalo-myo-synangiosis (EMS) treatment could be facilitated by bone marrow mesenchymal stem cells (MSCs) transplantation. Considering the advantages of biomaterials, we synthesized and modified a gelatin hydrogel for MSCs encapsulation. We then applied this hydrogel on the brain surface during EMS operation in rats with CCI, and evaluated its impact on cognitive performance and collateral circulation.

ORGANISM(S): Rattus norvegicus Homo sapiens

PROVIDER: GSE269005 | GEO | 2024/06/10

REPOSITORIES: GEO

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Enhanced Osteogenesis of Mesenchymal Stem Cells Encapsulated in Injectable Microporous Hydrogel

Project description:Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. Microporous hydrogel induced more robust osteogenic differentiation of MSCs and calcium mineral deposition than the nonporous hydrogel confirmed by alkaline phosphatase (ALP) assay and calcium assay. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that the microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.

2024-04-15 | GSE263939 | GEO

Towards optimized tissue regeneration: A new 3D printable bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate

Project description:Introduction: Autologous platelet concentrates (APC) are pro-angiogenic and can promote wound healing and tissue repair, also in combination with other biomaterials. However, challenging defect situations remain demanding. 3D bioprinting of an APC based bioink encapsulated in a hydrogel could overcome this limitation with enhanced physio-mechanical interface, growth factor retention/secretion and defect-personalized shape to ultimately enhance regeneration. Methods: This study used extrusion-based bioprinting to create a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate. Chemico-physical testing exhibited an amorphous structure characterized by high shape fidelity. Cytotoxicity assay and incubation of human osteogenic sarcoma cells (SaOs2) exposed excellent biocompatibility. ELISA analysis confirmed pro-angiogenic growth factor release of the printed constructs, and co-incubation with HUVECS displayed proper cell viability and proliferation. Chorioallantoic membrane (CAM) assay explored the pro-angiogenic potential of the prints in vivo. Detailed proteome and secretome analysis revealed a substantial amount and homologous presence of pro-angiogenic proteins in the 3D construct. Results: This study demonstrated a 3D bioprinting approach to fabricate a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate with high shape fidelity, biocompatibility, and substantial pro-angiogenic properties. Conclusion: This approach may be suitable for challenging physiological and anatomical defect situations when translated into clinical use.

2024-06-23 | PXD050629 | Pride

Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures

Project description:Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel with no known bioactive epitopes, Puramatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue

2016-12-12 | GSE81995 | GEO

Exercise intensity and sex alter neurometabolic, transcriptional, and functional recovery following traumatic brain injury.

Project description:In order to assess the impact of treadmill exercise on traumatic brain injury outcomes, we subjected male and female swiss webster mice to a controlled cortical impact (CCI), followed by 10 days of sedentary, low-, moderate-, or high-intensity treadmill exercise. Outcome measures included neurometabolic function, cognitive recovery, oxidative stress, pathophysiology, and single nuclei RNA sequencing (snRNA seq). The snRNA seq study was conducted on both male and female mice, and included a total of 2 replicates (each was a pool of 2 tissue samples) from each of the following groups: male sham sedentary, male CCI sedentary, male CCI low, male CCI high, female sham sedentary, female CCI sedentary, female CCI low, female CCI high. Our data reveal exercise intensity- and sex-dependent effects of treadmill exercise following injury. Transcriptomic changes were largely limited to the low-intensity exercised CCI males.

2023-08-01 | GSE226072 | GEO

Cellular Decoding of Simultaneous Cranial Mesenchyme and Osseous Architecture Reconstruction by Scaffolds

Project description:In this study, RNA sequencing was employed to investigate the differences in gene expression levels and patterns of cells recruited into suture-bony combined calvarial injury following the implatation of distinct types of commonly used calvarial scaffolds including gelatin methacryloyl hydrogel (GelMA), porous chitosan scaffold (CTS), and polylactic acid eletrospinning membrane (PLA).

2023-12-07 | GSE249260 | GEO

Single cell analysis of iPSC-derived cortical organoids in biofunctionalized gelatin hydrogels

Project description:Human neural organoid models have become an important tool for studying neurobiology. In this work, we compared Matrigel to an N-cadherin peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. Specifically, we compare five materials: (1) Matrigel, (2) GelMA-Cad with high crosslinker (HC), (3) GelMA-Cad with low crosslinker (LC), (4) GelMA HC and (5) GelMA LC. We determined that both mechanical properties and peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad produce higher numbers of neurogenic and ciliated radial glia and upper-layer excitatory neurons—an important population for modeling neurodegenerative disease—compared to GelMA and Matrigel controls.

2024-02-28 | E-MTAB-13828 | biostudies-arrayexpress

Single cell analysis of iPSC-derived cortical organoids in biofunctionalized gelatin hydrogels

2024-07-01 | E-MTAB-14203 | biostudies-arrayexpress

Matrix stiffness-dependent regulation of immunomodulatory genes in human MSCs is associated with the lncRNA CYTOR

Project description:Previous studies have demonstrated that the physical properties of biomaterials can be adjusted to program therapeutically relevant functions in encapsulated mesenchymal stromal cells (MSCs). However, the intracellular pathways affected by mechanical cues in this cell type are not well understood. An understanding of the pertinent factors involved would not only aid in the rational design of substrates but also uncover targetable mechanisms that can facilitate the engineering of MSCs for cell therapies. Here, a bone marrow-mimetic hydrogel is employed to systematically explore the stiffness-responsive transcriptome of MSCs. High matrix rigidity impedes integrin-collagen adhesions which yields changes in cell morphology that are characterized by a contractile network of actin proximal to the cell membrane. This results in a suppression of ECM-regulatory genes involved in the remodeling of collagen fibrils and an upregulation of secreted immunomodulatory factors. Moreover, an investigation of long non-coding RNAs reveals that CYTOR contributes to these stiffness-driven changes in gene abundance. A robust knockdown of CYTOR using antisense oligonucleotides enhances the expression of numerous mechanoresponsive cytokines and chemokines to levels exceeding what is achievable by modulating matrix stiffness alone. Taken together, these findings emphasize the utility in studying previously unexplored mechanisms of mechanotransduction to inform novel strategies for enhancing the efficacy of MSC-based therapies.

2024-08-21 | GSE255574 | GEO

Single-cell RNA sequencing and spatial transcriptomics reveal the osteoimmune microenvironment of biomaterial-mediated bone regeneration [scRNA-seq]

Project description:The bone-defect-repair process involves complex interaction between mesenchymal stem cells (MSCs) and immune cells, while the heterogeneity of osteoimmune microenvironment around implanted biomaterials remains elusive. By combining analysis of scRNA-seq and spatial transcriptomics technologies, we revealed that MgphiMSCs subpopulation served as the pioneers during the early stage of biomaterials-mediated bone defect healing process. They performed efficient osteogenic differentiation potential and had close interactions with immune cells. Remarkably, the MgphiMSCs could response to biomaterials-mediated osteoimmune microenvironment, rewired the polarization and osteoclastic differentiation of macrophages via midkine (MDK) signaling pathway. The inhibition of MDK activated the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple innate and adaptive immune-cell subsets exhibited close crosstalk between MgphiMSCs via SPP1 signaling pathway. These cellular profiles and interactions characterized in this study could broaden our understanding of the functional MSCs subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for the materials-designed strategies that target osteoimmune modulation.

2024-06-30 | GSE246475 | GEO

Single-cell RNA sequencing and spatial transcriptomics reveal the osteoimmune microenvironment of biomaterial-mediated bone regeneration [ST-seq]

2024-06-30 | GSE246096 | GEO

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