Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiRNA induced co-differentiation and cross-talk of adipose tissue-derived progenitor cells for 3D heterotypic pre-vascularized bone formation.

ABSTRACT: Engineered bone grafts require a vascular network to supply cells with oxygen, nutrients and remove waste. Using heterotypic mature cells to create these graftsin vivohas resulted in limited cell density, ectopic tissue formation and disorganized tissue. Despite evidence that progenitor cell aggregates, such as progenitor spheroids, are a potential candidate for fabrication of native-like pre-vascularized bone tissue, the factors dictating progenitor co-differentiation to create heterotypic pre-vascularized bone tissue remains poorly understood. In this study, we examined a three-dimensional heterotypic pre-vascularized bone tissue model, using osteogenic and endotheliogenic progenitor spheroids induced by miR-148b and miR-210 mimic transfection, respectively. Spheroids made of transfected cells were assembled into heterotypic structures to determine the impact on co-differentiation as a function of micro-RNA (miRNA) mimic treatment group and induction time. Our results demonstrated that miRNAs supported the differentiation in heterotypic structures, and that developing heterotypic structures is determined in part by progenitor maturity, as confirmed by gene and protein markers of osteogenic and endotheliogenic differentiation and the mineralization assay. As a proof of concept, miRNA-transfected spheroids were also bioprinted using aspiration-assisted bioprinting and organized into hollow structures to mimic the Haversian canal. Overall, the presented approach could be useful in fabrication of vascularized bone tissue using spheroids as building blocks.

SUBMITTER: Celik N

PROVIDER: S-EPMC8596330 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

miRNA induced 3D bioprinted-heterotypic osteochondral interface.

Project description:The engineering of osteochondral interfaces remains a challenge. MicroRNAs (miRs) have emerged as significant tools to regulate the differentiation and proliferation of osteogenic and chondrogenic formation in the human musculoskeletal system. Here, we describe a novel approach to osteochondral reconstruction based on the three-dimensional (3D) bioprinting of miR-transfected adipose-derived stem cell (ADSC) spheroids to produce a heterotypic interface that addresses the intrinsic limitations of the traditional approach to inducing zonal differentiation via the use of diffusible cytokines. We evaluated the delivery of miR-148b for osteogenic differentiation and the codelivery of miR-140 and miR-21 for the chondrogenic differentiation of ADSC spheroids. Our results demonstrated that miR-transfected ADSC spheroids exhibited upregulated expression of osteogenic and chondrogenic differentiation related gene and protein markers, and enhanced mineralization and cell proliferation compared to spheroids differentiated using a commercially-available differentiation medium. Upon confirmation of the osteogenic and chondrogenic potential of miR-transfected ADSC spheroids, using aspiration-assisted bioprinting, these spheroids were 3D bioprinted into a dual-layer heterotypic osteochondral interface with a stratified arrangement of distinct osteogenic and chondrogenic zones. The proposed approach holds great promise for the biofabrication of stratified tissues, not only for the osteochondral interfaces presented in this work, but also for other composite tissues and tissue interfaces, such as, but not limited to, the bone-tendon-muscle interface and craniofacial tissues.

| S-EPMC9588307 | biostudies-literature

3D Bioprinting for Vascularized Tissue-Engineered Bone Fabrication.

Project description:Vascularization in bone tissues is essential for the distribution of nutrients and oxygen, as well as the removal of waste products. Fabrication of tissue-engineered bone constructs with functional vascular networks has great potential for biomimicking nature bone tissue in vitro and enhancing bone regeneration in vivo. Over the past decades, many approaches have been applied to fabricate biomimetic vascularized tissue-engineered bone constructs. However, traditional tissue-engineered methods based on seeding cells into scaffolds are unable to control the spatial architecture and the encapsulated cell distribution precisely, which posed a significant challenge in constructing complex vascularized bone tissues with precise biomimetic properties. In recent years, as a pioneering technology, three-dimensional (3D) bioprinting technology has been applied to fabricate multiscale, biomimetic, multi-cellular tissues with a highly complex tissue microenvironment through layer-by-layer printing. This review discussed the application of 3D bioprinting technology in the vascularized tissue-engineered bone fabrication, where the current status and unique challenges were critically reviewed. Furthermore, the mechanisms of vascular formation, the process of 3D bioprinting, and the current development of bioink properties were also discussed.

| S-EPMC7287611 | biostudies-literature

Scalable Generation of Pre-Vascularized and Functional Human Beige Adipose Organoids.

Project description:Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom-up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre-vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self-organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein-1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter-scale beige adipose micro-tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.

| S-EPMC10625054 | biostudies-literature

Human adipose stromal-vascular fraction self-organizes to form vascularized adipose tissue in 3D cultures.

Project description:Native human subcutaneous adipose tissue (AT) is well organized into unilocular adipocytes interspersed within dense vascularization. This structure is completely lost under standard culture conditions and may impair the comparison with native tissue. Here, we developed a 3-D model of human white AT reminiscent of the cellular architecture found in vivo. Starting with adipose progenitors derived from the stromal-vascular fraction of human subcutaneous white AT, we generated spheroids in which endogenous endothelial cells self-assembled to form highly organized endothelial networks among stromal cells. Using an optimized adipogenic differentiation medium to preserve endothelial cells, we obtained densely vascularized spheroids containing mature adipocytes with unilocular lipid vacuoles. In vivo study showed that when differentiated spheroids were transplanted in immune-deficient mice, endothelial cells within the spheroids connected to the recipient circulatory system, forming chimeric vessels. In addition, adipocytes of human origin were still observed in transplanted mice. We therefore have developed an in vitro model of vascularized human AT-like organoids that constitute an excellent tool and model for any study of human AT.

| S-EPMC6510792 | biostudies-literature

Engineering of fully humanized and vascularized 3D bone marrow niches sustaining undifferentiated human cord blood hematopoietic stem and progenitor cells.

Project description:Hematopoietic stem and progenitor cells (HSPCs) are frequently located around the bone marrow (BM) vasculature. These so-called perivascular niches regulate HSC function both in health and disease, but they have been poorly studied in humans due to the scarcity of models integrating complete human vascular structures. Herein, we propose the stromal vascular fraction (SVF) derived from human adipose tissue as a cell source to vascularize 3D osteoblastic BM niches engineered in perfusion bioreactors. We show that SVF cells form self-assembled capillary structures, composed by endothelial and perivascular cells, that add to the osteogenic matrix secreted by BM mesenchymal stromal cells in these engineered niches. In comparison to avascular osteoblastic niches, vascularized BM niches better maintain immunophenotypically-defined cord blood (CB) HSCs without affecting cell proliferation. In contrast, HSPCs cultured in vascularized BM niches showed increased CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM) numbers. The vascularization also contributed to better preserve osteogenic gene expression in the niche, demonstrating that niche vascularization has an influence on both hematopoietic and stromal compartments. In summary, we have engineered a fully humanized and vascularized 3D BM tissue to model native human endosteal perivascular niches and revealed functional implications of this vascularization in sustaining undifferentiated CB HSPCs. This system provides a unique modular platform to explore hemato-vascular interactions in human healthy/pathological hematopoiesis.

| S-EPMC8488506 | biostudies-literature

Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds.

Project description:A virus-activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high-density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs.

| S-EPMC4122615 | biostudies-literature

Engineering a 3D Vascularized Adipose Tissue Construct Using a Decellularized Lung Matrix.

Project description:Critically sized defects in subcutaneous white adipose tissue result in extensive disfigurement and dysfunction and remain a reconstructive challenge for surgeons; as larger defect sizes are correlated with higher rates of complications and failure due to insufficient vascularization following implantation. Our study demonstrates, for the first time, a method to engineer perfusable, pre-vascularized, high-density adipose grafts that combine patient-derived adipose cells with a decellularized lung matrix (DLM). The lung is one of the most vascularized organs with high flow, low resistance, and a large blood-alveolar interface separated by a thin basement membrane. For our work, the large volume capacity within the alveolar compartment was repurposed for high-density adipose cell filling, while the acellular vascular bed provided efficient graft perfusion throughout. Both adipocytes and hASCs were successfully delivered and remained in the alveolar space even after weeks of culture. While adipose-derived cells maintained their morphology and functionality in both static and perfusion DLM cultures, perfusion culture offered enhanced outcomes over static culture. Furthermore, we demonstrate that endothelial cells seamlessly integrate into the acellular vascular tree of the DLM with adipocytes. These results support that the DLM is a unique platform for creating vascularized adipose tissue grafts for large defect filling.

| S-EPMC8482279 | biostudies-literature

Platelet-lymphocyte co-culture serves as an ex vivo platform of dynamic heterotypic cross-talk.

Project description:Platelets are well known for their roles in hemostasis and thrombosis, and are increasingly recognized for their abilities to interact with white blood cells during inflammatory diseases, via secreted soluble factors as well as cell-cell contact. This interaction has been investigated in animal models and patient samples and has shown to be implicated in patient outcomes in several diseases. Platelet-leukocyte co-cultures are widely used to study platelet-leukocyte interactions ex vivo. However, there is a paucity with regard to the systematic characterization of cell activation and functional behaviors of platelets and leukocytes in these co-cultures. Hence we aimed to characterize a model of platelet-leukocyte co-culture ex vivo. Human peripheral blood mononuclear cell (PBMC) and platelets were isolated and co-cultured for 5 days at 37 °C in the presence or absence of anti-CD3/CD28 antibodies or PHA. We evaluated PF-4 secretion and p-selectin expression in platelets as markers of platelet activation. Lymphocyte activation was assessed by cell proliferation and cell population phenotyping, in addition to platelet-lymphocyte aggregation. Platelet secretion and p-selectin expression is maintained throughout the co-culture, indicating that platelets were viable and reactive over the 5 days. Similarly PBMCs were viable and maintained proliferative capacity. Finally, dynamic heterotypic conjugation between platelets and T lymphocytes was also observed throughout co-culture (with a peak at days 3 and 4) upon T lymphocyte activation. In conclusion, this in vitro model can successfully mimic the in vivo interaction between platelets and T lymphocytes, and can be used to confirm and/or support in vivo results.

| S-EPMC9733731 | biostudies-literature

Spatial Growth Factor Delivery for 3D Bioprinting of Vascularized Bone with Adipose-Derived Stem/Stromal Cells as a Single Cell Source.

Project description:Encapsulating multiple growth factors within a scaffold enhances the regenerative capacity of engineered bone grafts through their localization and controls the spatiotemporal release profile. In this study, we bioprinted hybrid bone grafts with an inherent built-in controlled growth factor delivery system, which would contribute to vascularized bone formation using a single stem cell source, human adipose-derived stem/stromal cells (ASCs) in vitro. The strategy was to provide precise control over the ASC-derived osteogenesis and angiogenesis at certain regions of the graft through the activity of spatially positioned microencapsulated BMP-2 and VEGF within the osteogenic and angiogenic bioink during bioprinting. The 3D-bioprinted vascularized bone grafts were cultured in a perfusion bioreactor. Results proved localized expression of osteopontin and CD31 by the ASCs, which was made possible through the localized delivery activity of the built-in delivery system. In conclusion, this approach provided a methodology for generating off-the-shelf constructs for vascularized bone regeneration and has the potential to enable single-step, in situ bioprinting procedures for creating vascularized bone implants when applied to bone defects.

| S-EPMC10934245 | biostudies-literature

Generation of Vascularized Neural Organoids by Co-culturing with Mesodermal Progenitor Cells.

Project description:Organoids are three-dimensional (3D) constructs generated in stem cell cultures and are thought to mimic tissue and organ development in situ. However, until recently, they often exclusively recapitulated the development of the organ`s parenchyma without the major components of the organ stroma. Here, we describe a protocol to incorporate stromal components, first of all blood vessels, by co-culturing with induced pluripotent stem cell-derived mesodermal progenitor cells. For complete details on the use and execution of this protocol, please refer to Wörsdörfer et al. (2019).

| S-EPMC7580204 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data