Table 2 Summary of sources and culture conditions used in the development of various reproductive organoids

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]