Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

ABSTRACT: Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as function as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to the tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 that is crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation, verified through molecular experiments. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage.

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE206120 | GEO | 2023/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Articular cartilage regeneration by activated skeletal stem cells

Project description:Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.

2020-06-24 | GSE151303 | GEO

Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes

Project description:Osteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injury to the articular surface is a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.

2021-12-10 | GSE142045 | GEO

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

Project description:Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

| PRJNA849238 | ENA

Human PSC-derived articular cartilage chondrocytes scRNA-seq

Project description:Objectives Traditional approaches to study Progressive Pseudorheumatoid Arthropathy of Childhood (PPAC) failed to uncover how loss-of-function mutations in Wnt inducible secreted protein 3 (WISP3) cause premature cartilage failure in children. We developed a human induced pluripotent stem cell (hiPSC)-based model of cartilage development to elucidate pathological changes in WISP3-deficient articular cartilage tissues compared to WISP3-sufficient isogenic cartilage tissues. Methods We generated iPSCs from 2 patients with PPAC, and we corrected the disease-causing mutation in one of these lines using CRISPR/Cas9. We also created a WISP3-knockout human embryonic stem cell line. We generated articular cartilage tissues from these hPSCs by established directed differentiation methods. Bioinformatic analyses were used to identify differentially expressed genes (DEGs) and cell type abundances, which were validated by quantitative RT-qPCR and in situ hybridization. Results WISP3-deficient articular cartilage tissues exhibited significantly different transcriptomic profiles and cellular composition compared with their isogenic controls. WISP3-deficient cartilage transcriptomes exhibited enriched biological processes such as TGFb signaling and epithelial to mesenchymal transition. We validated increased expression of TGFb-related genes in WISP3-deficient cartilage, and determined that the abundance of chondrocyte subtypes was altered compared with isogenic controls. Conclusions We developed a robust and reproducible model of iPSC-derived cartilage development to better understand the role of WISP3 in cartilage biology, and the pathology of cartilage failure associated with loss of WISP3 in patients with PPAC. We identified several altered biological processes and signaling pathways in WISP3-deficient cartilage that can be validated in the future with additional patient-derived cell lines, or large animal models.

2023-08-24 | GSE230195 | GEO

Human iPSC can be differentiated in vitro to articular cartilage or to osteogenic organoids via the endochondral ossification transdifferentiation pathway

Project description:The ability to generate chondrocytes and osteoblasts from induced pluripotent stem cells (iPSCs) will provide insights into skeletal development and genetic skeletal disorders and generate cells for regenerative medicine applications. Here we describe a method that directs iPSC-derived sclerotome to chondroprogenitors in 3D pellet culture then to articular chondrocytes or, alternatively, along the growth plate cartilage pathway to become hypertrophic chondrocytes that can transdifferentiate to osteoblasts. Osteogenic organoids deposit and mineralize a collagen I extracellular matrix (ECM), mirroring in vivo endochondral bone formation. We have identified gene expression signatures at key developmental stages including chondrocyte maturation, hypertrophy and transdifferentiation to osteoblasts, and show that this system can be used to model genetic cartilage and bone disorders.

2023-05-02 | GSE219215 | GEO

Expression data from articular and growth plate cartilage

Project description:The aim of the current study was to identify molecular markers for articular cartilage that can be used for the quality control of tissue engineered cartilage. Therefore a genom-wide expression analysis was performed using RNA isolated from articular and growth plate cartilage, both extracted from the knee joints of minipigs. Keywords: Native material or primary cells isolated from articular cartilage and growth plate cartilage Articular and growth plate cartilage were taken for RNA extraction and hybridization on Affymetrix microarrays. Furthermore chondrocytes from each type of cartilage were isolated and cell culture was started and terminated at day 10 or day 20. Total RNA from cultivated cells was extracted, and hybridization on Affymetrix microarrays was performed.

2011-07-28 | E-GEOD-23492 | biostudies-arrayexpress

Self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids

Project description:Here, we developed a simple xeno- and feeder-free protocol for human hyaline cartilage production in vitro using hydrogel-cultured multi-tissue organoids (MTO). We investigate gene regulatory networks during spontaneous hiPSC-MTO differentiation using RNA sequencing and bioinformatic analyses. We find the interplays between BMPs and neural FGF pathways are associated with MTO phenotype transition. We recognize TGF-beta/BMP and Wnt signaling likely contribute to the long-term maintenance of cartilage growth and specific increase in articular cartilage development. By comparing MTO cartilage transcription signature with human lower limb chondrocytes, we observe MTO chondrocytes show strong correlation with fetal lower limb cartilage tissues. Collectively, our findings describe self-organized emergence of MTO hyaline cartilage, its associated molecular pathways, and spontaneous adoption of articular cartilage development trajectories by MTO.

2022-09-12 | GSE184007 | GEO

Expression data from articular and growth plate cartilage

2011-07-29 | GSE23492 | GEO

Gene expression plofile in human articular cartilage-derived cells cultured by different culture methods

Project description:Atelocollagen gel is often used for three-dimensional culture of articular cartilage-derived cells, but further knowledge is needed about the effect of atelocollagen gel on cells. We performed a microarray analysis using human articular cartilage-derived cells cultured in three different methods (2D culture, 3D culture with atelocollagen gel, and 3D culture without atelocollagen gel).

2021-02-01 | GSE154723 | GEO

Gene expression pattern analysis of rat articular cartilage and xiphoid cartilage

Project description:We performed RNA-Seq analysis to investigate the gene expression patterns of rat articular cartilage and xiphoid cartilage.

2021-06-17 | GSE178294 | GEO