Cartilage organoids for cartilage development and cartilage-associated disease modeling

Cartilage organoids have emerged as powerful modelling technology for recapitulation of joint embryonic events, and cartilage regeneration, as well as pathophysiology of cartilage-associated diseases. Recent breakthroughs have uncovered “mini-joint” models comprising of multicellular components and extracellular matrices of joint cartilage for development of novel disease-modifying strategies for personalized therapeutics of cartilage-associated diseases. Here, we hypothesized that LGR5-expressing embryonic joint chondroprogenitor cells are ideal stem cells for the generation of cartilage organoids as “mini-joints” ex vivo “in a dish” for embryonic joint development, cartilage repair, and cartilage-associated disease modelling as essential research models of drug screening for further personalized regenerative therapy. The pilot research data suggested that LGR5-GFP-expressing embryonic joint progenitor cells are promising for generation of cartilage organoids through gel embedding method, which may exert various preclinical and clinical applications for realization of personalized regenerative therapy in the future.

[1]  J. Marioni,et al.  Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease. , 2022, Cell stem cell.

[2]  R. Tuan,et al.  Articular Tissue-Mimicking Organoids Derived from Mesenchymal Stem Cells and Induced Pluripotent Stem Cells , 2022, Organoids.

[3]  F. Hou,et al.  Generation of mitochondria-rich kidney organoids from expandable intermediate mesoderm progenitors reprogrammed from human urine cells under defined medium , 2022, Cell & Bioscience.

[4]  Sien Lin,et al.  Alleviation of osteoarthritis by intra-articular transplantation of circulating mesenchymal stem cells. , 2022, Biochemical and biophysical research communications.

[5]  Kevin Wei,et al.  Precision medicine in rheumatoid arthritis. , 2022, Best practice & research. Clinical rheumatology.

[6]  Juan Luo,et al.  BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids , 2022, Cell death discovery.

[7]  Jian Luo,et al.  The proton-activated G protein-coupled receptor GPR4 regulates the development of osteoarthritis via modulating CXCL12/CXCR7 signaling , 2022, Cell Death & Disease.

[8]  S. Houser,et al.  Flow-induced endothelial mitochondrial remodeling mitigates mitochondrial reactive oxygen species production and promotes mitochondrial DNA integrity in a p53-dependent manner , 2022, Redox biology.

[9]  Roberto L. Flores,et al.  Self-assembling human skeletal organoids for disease modeling and drug testing. , 2021, Journal of biomedical materials research. Part B, Applied biomaterials.

[10]  Wenbo Jiang,et al.  Generating 3D-cultured organoids for pre-clinical modeling and treatment of degenerative joint disease , 2021, Signal Transduction and Targeted Therapy.

[11]  G. Kerckhofs,et al.  Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects , 2021, Stem cell research & therapy.

[12]  A. Vegoe,et al.  Self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids , 2021 .

[13]  P. Ertl,et al.  Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research. , 2021, Lab on a chip.

[14]  N. Montserrat,et al.  Mini‐organs forum: how to advance organoid technology to organ transplant community , 2021, Transplant international : official journal of the European Society for Organ Transplantation.

[15]  A. Barbero,et al.  Nose to Spine: spheroids generated by human nasal chondrocytes for scaffold-free nucleus pulposus augmentation. , 2021, Acta biomaterialia.

[16]  Joseph Christakiran Moses,et al.  Overcoming the Dependence on Animal Models for Osteoarthritis Therapeutics – The Promises and Prospects of In Vitro Models , 2021, Advanced healthcare materials.

[17]  M. Grimes,et al.  Craniofacial cartilage organoids from human embryonic stem cells via a neural crest cell intermediate , 2021, bioRxiv.

[18]  Juan Luo,et al.  Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer , 2021, Cell & Bioscience.

[19]  P. Ordóñez-Morán,et al.  Biomaterials for intestinal organoid technology and personalized disease modelling. , 2021, Acta biomaterialia.

[20]  Y. Maugars,et al.  Osteoarthritis: from upcoming treatments to treatments yet to come. , 2021, Joint bone spine.

[21]  G. Ming,et al.  Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells. , 2021, Cell stem cell.

[22]  Keita Ito,et al.  De novo Neo-hyaline-cartilage from Bovine Organoids in Viscoelastic Hydrogels. , 2021, Acta biomaterialia.

[23]  F. Luyten,et al.  Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo. , 2021, Biomaterials.

[24]  N. Barker,et al.  A genome-scale CRISPR screen reveals factors regulating Wnt-dependent renewal of mouse gastric epithelial cells , 2021, Proceedings of the National Academy of Sciences.

[25]  H. Meng,et al.  Potential and recent advances of microcarriers in repairing cartilage defects☆ , 2021, Journal of orthopaedic translation.

[26]  A. O’Connor,et al.  The challenge of cartilage integration: understanding a major barrier to chondral repair. , 2020, Tissue engineering. Part B, Reviews.

[27]  F. Guilak,et al.  Formation of Osteochondral Organoids from Murine Induced Pluripotent Stem Cells. , 2020, Tissue engineering. Part A.

[28]  Cindy C. Guo,et al.  High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue , 2020, Cell.

[29]  H. Clevers,et al.  Establishment of patient-derived cancer organoids for drug-screening applications , 2020, Nature Protocols.

[30]  Jerry C. Hu,et al.  Collagen: quantification, biomechanics and role of minor subtypes in cartilage , 2020, Nature Reviews Materials.

[31]  S. Allart,et al.  Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients , 2020, Frontiers in Cell and Developmental Biology.

[32]  Ashish Ranjan Sharma,et al.  Differential Expression Patterns of Rspondin Family and Leucine-Rich Repeat-Containing G-Protein Coupled Receptors in Chondrocytes and Osteoblasts , 2020, Cell journal.

[33]  L. Baptista,et al.  Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks. , 2020, World journal of stem cells.

[34]  F. Luyten,et al.  Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing , 2019, Advanced science.

[35]  Shuibing Chen,et al.  Organoid-based chemical approach to dissect the mechanism controlling cellular dynamics , 2019, Journal of molecular cell biology.

[36]  C. Xinaris.  Organoids for replacement therapy: expectations, limitations and reality. , 2019, Current opinion in organ transplantation.

[37]  S. Mundlos,et al.  Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes , 2019, Stem cell reports.

[38]  N. Turner,et al.  Regulation of mitochondrial metabolism in murine skeletal muscle by the medium‐chain fatty acid receptor Gpr84 , 2019, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  M. Montrose,et al.  Trefoil factor 2 activation of CXCR4 requires calcium mobilization to drive epithelial repair in gastric organoids , 2019, The Journal of physiology.

[40]  A. van Oudenaarden,et al.  An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity , 2019, Nature Medicine.

[41]  Austin J. Ramme,et al.  Age-related inflammation triggers skeletal stem/progenitor cell dysfunction , 2019, Proceedings of the National Academy of Sciences.

[42]  J. I. Izpisúa Belmonte,et al.  Organoids — Preclinical Models of Human Disease , 2019 .

[43]  Alyssa J. Miller,et al.  Generation of lung organoids from human pluripotent stem cells in vitro , 2019, Nature Protocols.

[44]  Chiara Sabatti,et al.  Organoid Modeling of the Tumor Immune Microenvironment , 2018, Cell.

[45]  F. Guilak,et al.  Osteoarthritis as a disease of the cartilage pericellular matrix. , 2018, Matrix biology : journal of the International Society for Matrix Biology.

[46]  Alan J. Grodzinsky,et al.  Cartilage diseases. , 2018, Matrix biology : journal of the International Society for Matrix Biology.

[47]  S. Yamaguchi,et al.  Age-dependent differences in response to partial-thickness cartilage defects in a rat model as a measure to evaluate the efficacy of interventions for cartilage repair , 2018, Cell and Tissue Research.

[48]  Jiaqian Wu,et al.  Profiling of Stem/Progenitor Cell Regulatory Genes of the Synovial Joint by Genome-Wide RNA-Seq Analysis , 2018, BioMed research international.

[49]  L. Baptista,et al.  Adult Stem Cells Spheroids to Optimize Cell Colonization in Scaffolds for Cartilage and Bone Tissue Engineering , 2018, International journal of molecular sciences.

[50]  Y. Taniyama,et al.  Source of Chronic Inflammation in Aging , 2018, Front. Cardiovasc. Med..

[51]  Anthony Atala,et al.  Self‐assembled liver organoids recapitulate hepatobiliary organogenesis in vitro , 2018, Hepatology.

[52]  Jennifer L Hu,et al.  Opportunities for organoids as new models of aging , 2018, The Journal of cell biology.

[53]  Hans Clevers,et al.  Disease Modeling in Stem Cell-Derived 3D Organoid Systems. , 2017, Trends in molecular medicine.

[54]  Hans Clevers,et al.  Designer matrices for intestinal stem cell and organoid culture , 2016, Nature.

[55]  J. Schrooten,et al.  Bioinspired seeding of biomaterials using three dimensional microtissues induces chondrogenic stem cell differentiation and cartilage formation under growth factor free conditions , 2016, Scientific Reports.

[56]  Hans Clevers,et al.  Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation , 2016, Nature Protocols.

[57]  M. Takasato,et al.  Generation of kidney organoids from human pluripotent stem cells , 2016, Nature Protocols.

[58]  Hans Clevers,et al.  Modeling Development and Disease with Organoids , 2016, Cell.

[59]  J. Estaquier,et al.  NF-κB pathway controls mitochondrial dynamics , 2015, Cell Death and Differentiation.

[60]  J. Nunnari,et al.  Determinants and functions of mitochondrial behavior. , 2014, Annual review of cell and developmental biology.

[61]  Mingyao Liu,et al.  GPR126 Protein Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Receptor Signaling* , 2014, The Journal of Biological Chemistry.

[62]  C. Franceschi,et al.  Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[63]  C. Weyand,et al.  T-cell aging in rheumatoid arthritis , 2014, Current opinion in rheumatology.

[64]  W. de Lau,et al.  Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. , 2013, Cell reports.

[65]  C. Weyand,et al.  The Janus Head of T Cell Aging – Autoimmunity and Immunodeficiency , 2013, Front. Immunol..

[66]  Jerry C. Hu,et al.  Unlike Bone, Cartilage Regeneration Remains Elusive , 2012, Science.

[67]  Jian Luo,et al.  Regulation of bone formation and remodeling by G-protein-coupled receptor 48 , 2009, Development.

[68]  H. Mizumoto,et al.  Development of articular cartilage grafts using organoid formation techniques. , 2008, Transplantation proceedings.

[69]  M. McKee,et al.  Aged bovine chondrocytes display a diminished capacity to produce a collagen‐rich, mechanically functional cartilage extracellular matrix , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[70]  C. Weyand,et al.  Stem cell aging and autoimmunity in rheumatoid arthritis. , 2004, Trends in molecular medicine.

[71]  S. Gabriel,et al.  Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. , 2002, Arthritis and rheumatism.

[72]  B. Zimmermann,et al.  The extracellular matrix in cartilage organoid culture: biochemical, immunomorphological and electron microscopic studies. , 1991, Matrix.

[73]  B. Zimmermann,et al.  Endochondral mineralization in cartilage organoid culture. , 1990, Cell differentiation and development : the official journal of the International Society of Developmental Biologists.

[74]  B. S. Schon,et al.  Modular Tissue Assembly Strategies for Biofabrication of Engineered Cartilage , 2016, Annals of Biomedical Engineering.