Table 2.
Summary of sources and culture conditions used in the development of various reproductive organoids
| Organoids | Source | Culture conditions | Cell types in organoids | Matrix | Generation efficiency | Reference |
|---|---|---|---|---|---|---|
| Ovarian cancer | Ovarian cancer tissue |
Establishment: Advanced DMEM/F12, Glutamax, HEPES, Noggin, Rspo1, WNT3A, B27, FGF10, bFGF, nicotinamide, N-acetyl-L-cysteine, A83–01, Heregulinβ-1, hEGF, IGF-1, HGF, Forskolin, Hydrocortisone, NRG1, p38i (SB203580), β-Estradiol, Y-27632 Test components: carboplatin, paclitaxel, alpelisib, pictilisib, MK2206, AZD8055, Niraparib, adavosertib, gemcitabine, doxorubicin, nutlin-3 |
Disease and original tumor phenotype |
Cultrex growth factor reduced BME type 2 |
33–65% | [15, 16] |
| Fallopian tube | human iPSC lines (87iCTR-n3, 01iMEC-n4, 14iCTR-n6) |
Mesoderm induction: Activin A, CHIR99021, Y27632 Intermediate mesoderm induction: BMP4, CHIR99021, Y27632 The fallopian tube epithelial cells differentiation: WNT4, Follistatin Establishment: DMEM/F12, reconstituted Ultroser, Y-27632, estrogen, progesterone, conditioned media from FTE cells Maturation: cultured in 3D Matrigel for an extended period with estrogen and progesterone supplemented media |
Ciliated (TUBB4A and FOXJ1) cells secretory (PAX8) cells |
Matrigel | NR | [22] |
| Lin − EPCAM+ FTE cells |
Establishment: Advanced DMEM/F12, GlutaMAX, B27, EGF, TGFBR1 Kinase Inhibitor IV, Y-27632 Differentiation: RSPO1 |
PAX8+ secretory cells acetylated tubulin (AcTUB) + ciliated cells |
Matrigel | NR | [23] | |
| Epithelial progenitor (EpCAM+) cell |
Establishment: Advanced DMEM/F12, conditioned human Wnt3A medium, conditioned human RSPO1 medium, GlutaMAX, B27, N2, human EGF, human noggin, human FGF10, nicotinamide, Y-27632, TGF-β R Kinase Inhibitor IV hormonal stimulation: beta-oestradiol, progesterone |
Pax8-positive secretory cells Pax8 negative, acetylated tubulin-positive ciliated cells |
Matrigel | NR | [25] | |
| Endometrium | the mouse endometrial glandular-type fragments |
Establishment: DMEM/F12, GlutaMAX, B27, ITS, FGF10, nicotinamide, WNT3A; R-spondin 1, Noggin, A83–01 Hormonal stimulation: beta-oestradiol, progesterone |
secretory cells ciliated cells |
Matrigel | NR | [4] |
| the human endometrial glandular-type fragments | Establishment: WNT3A; R-spondin 1, EGF, FGF10, Noggin, A83–01, ITS, N-acetyl-L-cysteine, p38 inhibitor SB202190Hormonal stimulation: beta-oestradiol, progesterone |
secretory cells ciliated cells |
Matrigel | NR | [4] | |
| Dissociated endometrial cancer cells |
Establishment: DMEM/F12, B27, Glutamax, N-acetyl cysteine, Primocin, nicotinamide, A 83–01, SB 202190, Y- 27632, 17-A estradiol Test components: Megestrol acetate, fulvestrant, letrozole, mifepristone, erlotinib, linsitinib; Selleckchem, BGJ-398, BBI608, cisplatin, paclitaxel. |
Epithelial cells mesenchymal derivatives |
growth factor reduced BME type 2 | NR | [26] | |
| Endometrial epithelial cells |
Establishment: ExM: Advanced DMEM/F12, N2, B27 minus vitamin A, Primocin, N-Acetyl-L-cysteine, L-glutamine, Recombinant human EGF, Recombinant human Noggin, Recombinant human Rspondin-1, Recombinant human FGF-10, Recombinant human HGF, ALK-4, −5, −7 inhibitor A83–01, Nicotinamide Differentiation: β-oestradiol, progesterone, cAMP, prolactin, human chorionic gonadotropin, human placental lactogen Hormonal stimulation: β-oestradiol, progesterone, cAMP |
secretory (PAEP+) cells ciliated (acetylated-α-tubulin+) cells |
Matrigel | 100% | [3] | |
|
Endometriotic epithelial cells (ECT-O) Epithelial cell from hyperplastic endometrium (HYP-O) |
Establishment; SOM; DMEM/F12 + L-glutamine and Hepes, RSPO1-conditioned medium, Noggin, B27, N2, Glutamax, Insulin Transferrin Selenium, Nicotinamide, A83–01, N-acetyl L-cysteine, EGF, bFGF, FGF-10, SB202190 (p38i) |
secretory cells ciliated cells |
Matrigel |
ECT-O; 60% HYP-O; 70% |
[24] | |
| Epithelial cell from endometrial cancer |
Establishment; SOM; DMEM/F12 + L-glutamine and Hepes, RSPO1-conditioned medium, Noggin, B27, N2, Glutamax, Insulin Transferrin Selenium, Nicotinamide, A83–01, N-acetyl L-cysteine, EGF, bFGF, FGF-10, insulin-like growth factor 1 (IGF1), hepatocyte growth factor (HGF) and lipids Test components: paclitaxel, 5-fluorouracil, carboplatin, doxorubicin and everolimus |
NR | Matrigel | EC-O; 40%; | [24] | |
| Trophoblast | villous cytotrophoblasts (vCTBs), purified from pooled first-trimester placental tissues |
Establishment: basic trophoblast organoid medium (b-TOM): advanced DMEM/F12, HEPES, B27, N2, glutamine, R-spondin, A83–01, rhEGF, rmHGF, prostaglandin E2, CHIR99021, Noggin, EGF, R-spondin, CHIR99021, A83–01 Differentiation: lacking R-spondin and CHIR99021, inhibitor of Wnt response-1 (IWR-1) |
cytotrophoblasts (CTB) syncytiotrophoblasts (STB) extravillous trophoblast (EVT) |
Matrigel | 100% | [5] |
| trophoblast-enriched cell suspensions |
Establishment: basal trophoblast organoid medium (TOM): EGF, FGF2, CHIR99021, A83–01, R-spondin 1, HGF, PGE2, Y-27632, nicotinamideDifferentiation: EVT differentiation medium (EVTM): advanced DMEM/ F12, 2-mercaptoethanol, BSA, ITS-X, NRG1, A83–01, KSR. Typically after days 7–10, the medium was changed to EVTM without NRG1 for a further 7–10 days. |
syncytiotrophoblast (SCT) villous cytotrophoblast (VCT) HLA-G+ extravillous trophoblast cells (EVT) cells |
Matrigel | 91% | [27] | |
| Cervical organoid | cervical clear cell carcinoma cells |
Establishment: DMEM/F12, human EGF, R-spondin1, Noggin, Y27632, Jagged-1, l-glutamine Test components: paclitaxel, cisplatin, gemcitabine hydrochloride, crizotinib, and SU11274 |
Atypical cells with clear cytoplasm concordant with morphological features of the original tumor |
Matrigel | [28] |
Abbreviations: A.83–01 Selective inhibitor of ALK4,5,7, EGF Epidermal growth factor, FGF Fibroblast growth factor, HGF Hepatocyte growth factor, NRG1 Neuregulin-1, Rho-KI Rho kinase inhibitor, RSPO1 R-spondin-1, NR Not-reported