Organoids as Innovative Models for Bone and Joint Diseases
Abstract
:1. Introduction
1.1. Bone and Joint Biology
1.2. Comparison of Research Models In Vitro
2. Organoid
2.1. Cell Sources for Organoid Culture
2.2. Organoid Culture Techniques
2.3. Organoid Culture Techniques
Organoid Type | Special Media Components # | Culture Techniques | References |
---|---|---|---|
The organoids derived from PSCs | |||
Intestine | activin A, Wnt-3A, FGF-4, EGF, NOG, R-spondin 1, RA, CHIR99021 | Solid matrix; ALI | [42,53,54] |
Gastric | activin A, Wnt-3A, FGF4, NOG, gastrin, nicotinamide, EGF, RA, CHIR99021, Y-27632 | Solid matrix | [33,55] |
Liver | activin A, BMP-4, FGF-4, NOG, FGF-2, HGF, Y-27632, CHIR99021 | Solid matrix; ALI | [43,56,57] |
Pancreas | activin A, BMP-4, FGF-4, Wnt-3A, NOG, Y-27632, CHIR99021, FGF-10, dorsomorphin, LDN193189, SANT-1, RA, EGF, Nicotinamide, KGF, MSC2530818, ZnSO4 | Solid matrix; ALI | [43,58] |
Lung | Activin A, Wnt-3A, FGF-4, NOG, SB431542, SU5402, SANT-2, SAG, SHH, RA | Solid matrix | [59] |
Mammary gland | hydrocortisone, insulin, FGF-10, HGF, pTHrP, FGF-2, heparin, prolactin | Suspension | [60] |
Kidney | Activin A, BMP-4, BMP-7, FGF-2, FGF-8, FGF-9, HGF, IDE-1, JAG-1, NOG, Y-27632, CHIR99021, DAPT, IGF-1, Wnt-4, IWR-1, RA, SB431542 | Suspension; ALI | [61,62] |
Fallopian | activin A, CHIR99021, Y-27632, BMP-4, Wnt-4, Wnt-3A, follistatin, estrogen, progesterone | Solid matrix | [63] |
Inner ear | BMP-4, SB431542, FGF-2, LDN193189, Y-27632 | Solid matrix | [64] |
Thyroid | Activin A, NOG, SB431542, Wnt-3A, KGF, FGF-10, BMP-4, EGF, FGF-2, HSS, IGF-1, insulin, Y-27632, dorsomorphin, CHIR99021, RA, TSH, R-spondin-1 | Solid matrix | [30,65] |
Blood vessels | Wnt-3A, BMP-4, VEGF-A, CHIR99021, FGF-2, Y-27632, forskolin | Solid matrix | [27] |
Optic cup | BMP-4, RA, Wnt-3A, Nodal, DAPT | Suspension | [45] |
Brain | Forebrain: dorsomorphine, A83-01, Wnt-3A, CHIR99021, SB431542, BDNF, GDNF, TGF-β, c-AMP. Midbrain: LDN193189, SB431542, SHH, purmorphamine, FGF-8, CHIR99021, BDNF, GDNF, c-AMP. Hypothalamus: LDN193189, SB431542, 1-Thioglycerol, Wnt-3A, SHH, FGF-2 purmorphamine | Suspension | [47,66,67] |
The organoids derived from ASCs | |||
Intestine | EGF, NOG, R-spondin 1, Wnt-3A, JAG-1, Y-27632, CHIR99021, valproic acid | Solid matrix; ALI | [14,41,68] |
Gastric | EGF, NOG, R-Spondin 1, Wnt-3A, FGF-10, Y-27632 | Solid matrix; ALI | [41,69] |
Liver | EGF, NOG, R-Spondin 1, Wnt-3A, FGF-10, HGF, nicotinamide, gastrin | Solid matrix | [70] |
Pancreas | EGF, NOG, R-Spondin 1, Wnt-3A, FGF-10, nicotinamide, Y-27632 | Solid matrix | [69] |
Lung | Wnt3a, R-spondin 1, and NOG, Y-27632, FGF-7, FGF-10, SB202190, KGF, cAMP, monothioglycerol, CHIR99021, ascorbic acid, dexamethasone, IBMX | Solid matrix; ALI | [44,71] |
Mammary gland | heparin, EGF, FGF2, insulin, hydrocortisone, cholera toxin, ciproflaxin, Nrg1, NOG, R-spondin 1 | Solid matrix | [72,73] |
Kidney | EGF, FGF-10, Y-27632, SB431542, A83-01 | Solid matrix | [74] |
Fallopian | Y-27632, EGF, NOG, FGF-10, nicotinamid, SB431542 | Solid matrix | [75] |
Bladder | EGF, R-spondin 1, NOG, A83-01, FGF-10, FGF-2, SB202190 | Solid matrix; ALI | [25,76] |
Prostate | EGF, R-spondin 1, NOG, A83-01, FGF-10, FGF-2, PGE2, SB202190, nicotinamide | Solid matrix | [77] |
Special Media Components | Functions |
---|---|
Activin A, BMP-4 | As important members of the TGF-β superfamily, Activin A and BMP4 can induce the embryonic stem cells to differentiate into different germ layers. |
Wnt-3A | Wnt-3A modulates embryonic development, cell growth, cell differentiation, and tumorigenesis via the canonical Wnt pathway. |
Noggin | Noggin regulates the germ-layer-specific derivation of embryonic stem cells and acts as an antagonist of BMP during development. |
Y-27632 | The ROCK inhibitor improves the survival of human ESC monolayers at the initiation of differentiation. |
FGF | The FGF family plays a central role during prenatal development, postnatal growth, and the regeneration of a variety of tissuesby promoting cellular proliferation and differentiation. |
EGF | EGF is a protein that stimulates cell growth and differentiation by binding to its receptor. |
HGF | HGF has a strong mitogenic ability to regulate cell growth and cell motility on hepatocytes and primary epithelial cells. |
Gastrin | Gastrin acts as a growth factor in organoid culture and stimulates the proliferation of cells. |
Retinoic acid | Retinoic acid helps to transform cell types from the proliferative profile to the maturation profile by inducing differentiation. |
SB202190 | A p38 inhibitor induces cardiomyocyte differentiation from human embryonic stem cells. |
R-spondin 1 | R-spondin proteins are a secreted agonist of the Wnt/β-catenin signaling pathway. |
CHIR99021 | The small molecule is the GSK 3 inhibitor and the WNT activator, which can promote the differentiation of insulin-producing cells and cardiomyocytes from human PSCs. |
Nicotinamide | A water-soluble vitamin is an active component of the coenzymes NAD and NADP and also act as an inhibitor of sirtuins. |
SANT-1 | SANT-1 is a cell-permeable antagonist that binds directly to smoothened and inhibits the hedgehog signaling to promote β cell differentiation. |
LDN193189 | A selective BMP signaling inhibitor inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3. |
Dorsomorphin | An inhibitor of the AMPK and BMP pathways is used to promote special cell differentiation. |
KGF | KGF supports ductal specification by upregulating KRT19 and increasing culture homogeneity. |
MSC2530818 | A WNT inhibitor increases expression. |
3. Bone-Related Organoid Culture
3.1. Bone-Related Organoids from PSCs
3.2. Bone-Related Organoids from ASCs
3.3. Bone-Related Organoids from Bone Precursor Cells
3.4. Bone-Related Organoids on a Chip
4. Bone Disease Organoid Models
5. Potential Applications of Bone Disease Organoid Models
5.1. Drug Screening
5.2. Precision Medicine
6. Perspectives and Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Disease Types | Features | |
---|---|---|
Bone disorders | ||
Fracture | a break in the bone caused by stress | |
Osteoporosis | a degenerative disease, characterized by the porosity and brittleness of bone in the aged | |
Osteomyelitis | an infectious disease caused by the infectious organism Staphylococcus aureus (S. aureus) | |
Osteomalacia | rickets in adults is caused by the inadequate mineralization of the bone | |
Osteitis fibrosa cystica | a disease in which bone is replaced by fibrous tissue | |
Osteosarcoma | a disorder in which bone tissue grows uncontrollably (either malignant or benign) | |
Multiple myeloma | one of the broadest hematologic cancers, characterized by anemia, hypercalcemia, malignant bone infiltration, increased infectious susceptibility, and kidney failure | |
Joint disorders | ||
Osteoarthritis | a ubiquitous noninflammatory degenerative joint disease, characterized by the progressive deterioration of the whole joint | |
Bursitis | an inflammation of the lubricating sac located around joints, the synovial bursa, or between tendons and muscles or bones | |
Infectious arthritis | a set of arthritis caused by exposure to certain microorganisms | |
Rheumatoid arthritis | a chronic, frequently progressive autoinflammatory disease in which inflammation and the thickening of the synovial membranes cause irreversible damage to the joint capsule | |
Several other types | psoriatic arthritis | resembles rheumatoid arthritis, but lacks rheumatoid factors in the blood |
ankylosing spondylitis |
3D Self-Organizing Structures or Organoids | Cells Source | Special Media Components | Culture Techniques | References |
---|---|---|---|---|
Human cartilaginous organoids | Human iPSCs or ESCs | CHIR99021, FGF-2, RA, AA, β-Mercaptoethanol, TGF-β1, FGF-2, BMP-2, GDF5 | Solid matrix | [51] |
Murine osteochondral organoids | murine iPSC | TGF-β3, BMP-2, AA, β-mercaptoethanol, β-glycerophosphate, dexamethasone | Solid matrix | [78] |
Bone spheroids | Osteoblasts | TGF-β1, ITS+ | - | [79] |
Woven bone organoids | Human BMSCs | AA, dexamethasone, and β-glycerophosphate | Solid matrix | [52] |
Trabecular bone organoids | Human osteoblasts and osteoclasts | VD3, PGE2, AA, RANKL, β-glycerophosphate, M-CSF | Solid matrix | [80,81] |
Bone marrow organoids | human BMSCs or human CB-BFs | 2-phosphate–ascorbic acid, dexamethasone, and TGF-β1 or TGF-β3 | in vivo model | [82,83,84] |
Bone organoids | Osteoblasts, osteoclasts, endothelial cells | M-CSF, RANKL | Solid matrix | [85] |
Callus organoid | PDCs | ascorbate-2 phosphate, dexamethasone, proline, Y27632, BMP-2, GDF5, TGF- β1, BMP-6, FGF-2 | Solid matrix | [86] |
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Huang, J.; Zhang, L.; Lu, A.; Liang, C. Organoids as Innovative Models for Bone and Joint Diseases. Cells 2023, 12, 1590. https://doi.org/10.3390/cells12121590
Huang J, Zhang L, Lu A, Liang C. Organoids as Innovative Models for Bone and Joint Diseases. Cells. 2023; 12(12):1590. https://doi.org/10.3390/cells12121590
Chicago/Turabian StyleHuang, Jie, Lingqiang Zhang, Aiping Lu, and Chao Liang. 2023. "Organoids as Innovative Models for Bone and Joint Diseases" Cells 12, no. 12: 1590. https://doi.org/10.3390/cells12121590