Table 1 The induced differentiation of hAECs in vitro

Liver

Hepatocyte-like cells

Expressing hepatocyte-like cell functional genes: albumin, CYP1A1, CYP1A2, c-met, and transcription factors: HNF3, HNF4, C/EBPa, and HNF1

Using a combined approach of dexamethasone, HGF, IGF, and other cytokines

[31]

Hepatocyte-like cells

Expressing hepatic related genes: albumin, A1AT, CYP3A4, 3A7, 1A2, 2B6, and the asialoglycoprotein receptor 1 (ASGPR1)

Using extracellular matrix substrates; cocultured with mouse hepatocytes

[32]

Hepatic differentiation

Displayed a similar hepatic morphology; expressing specific hepatic genes: albumin, CYP7A1, and CYP3A4

Using a specific hepatic differentiation protocol

[33]

Hepatic differentiation

The formation of bile canaliculi; secreting albumin; uptaking low-density lipoprotein and showing inducible CYP3A4 and CYP2C9 enzymatic activities

Using four-step hepatic differentiation protocol

[34]

Hepatic sinusoidal endothelial cells

Forming capillary-like structure in vitro and differentiate into HSECs in vivo

Under proangiogenic conditions

[35]

Pancreas

Insulin-producing cells

The formation of three-dimensional (3D) spheroids; producing pancreatic endocrine hormones; releasing C-peptide under hyperglycemic condition

Culturing on extracellular matrix

[36]

Pancreatic lineage cells

Expressing pancreatic endoderm and progenitor genes: NKX6.1, NeuroD1, and pancreatic lineage genes: PDX1, SOX17, RFX6

Combination of transcription factor PDX1 with activin A or nicotinamide

[37]

Islet-like cells

Expressing the endocrine-related genes: PDX1, ngn3, insulin, and glucagon; secreting insulin in response to high glucose exposure

Using DMEM with different supplements and suspension culture

[38]

Islet-like cell clusters

Expressing pancreatic development-related genes: PDX1, NKX6-1, NEUROG3, PAX6, INS, and GCG; insulin positive and sensitive to glucose

Adding nicotinamide plus betacellulin

[39]

Pancreatic cells

Expressing pancreatic differentiation related genes: NKX6.1, SOX17, RFX6, NEUROD1, and PAX4

Inducing endogenous PDX1 expression, EGF, and poly-l-ornithine

[40]

Acinar cells

Expressing α-amylase and mucins

Cocultured with submandibular gland acinar cells using a double-chamber system

[41]

Insulin secreting cells

Expressing PDX1 and beta2 microglobulin; secreting insulin

Treated with nicotinamide and N2 supplement

[42]

Ovary

Germ cell-like cells

Expressing germ cell-specific genes: GDF9, DAZL, and SCP3; producing estradiol

Medium supplemented with 5% human follicular fluid

[43]

Follicle-like structure

Expressing germ cell-specific genes DAZL and GDF9; secreting estradiol

Medium supplemented with 5% human follicular fluid

[44]

Germ cell-like cells (diploid cells)

Expressing germ cell-specific protein DAZL, oocyte-specific proteins GDF9 and ZP3, meiosis-specific proteins DMC1 and SCP3

Cultured in medium containing serum substitute supplement (SSS)

[45]

Eyes

Corneal epithelial-like cells

Showing a similar morphology to hCECs; expressing CK3/12, CK14, CK19, and P63

Cultured with human corneal epithelial cells (hCECs) in a Transwell coculture system

[46]

Corneal epithelial-like cells

Expressing CK3/12

Seeded onto rabbit corneal stroma

[47]

Corneal epithelial-like cells

Expressing CK3/12

Adding the conditioned medium of spontaneously immortalized human corneal epithelial cells (S-ihCECs)

[48]

Conjunctival epithelium-like cells

Showed conjunctival epithelium phenotype; producing mu5ac

Cultured with induced-denuded conjunctival matrix and conjunctival homogenate

[49]

Nervous system

Neuronal differentiation

Expressing neural cell markers NSE and NeuN

Adding noggin, bFGF, and retinoic acid

[50]

Neuronal differentiation

Upregulation of transcription factors involving in neuronal differentiation

Treated with rosmarinic acid

[51]

Cortical progenitors

Expressing cortical neuron-specific proteins: TBR2, OTX2, NeuN, and β-III-tubulin

Adding growth factors and small molecules

[52]

Schwann-like cells

Exhibiting a typical bipolar or tripolar morphology; expressing S-100; increasing the expressions of BDNF and GDNF

Cocultured with Schwann cells (SCs)

[53]

Bone

Osteogenic differentiation

Increasing cellular ALP activity and extracellular mineralization; expressing Runx2, osterix, ALP, collagen I, and OPN

Cultured with classic osteogenic medium

[54]

Cartilage differentiation

Expressing cartilage markers: aggrecan, Sox9, CEP-68, and type II and X collagens; promoting matrix synthesis

Treated with BMP-7 or TGF-β1

[55]

Osteoblasts

Upregulating Runx2, ALP, and OPN

Mechanical stretch

[56]

Respiratory

Polarized airway-like cells

Forming 3D structures; expressing CFTR and possessing functional iodide/chloride (I⁻/Cl⁻) ion channels

Cultured with small airway growth medium (SAGM)

[57]

Heart

Cardiomyocyte-like cells

Expressing cardiac-specific genes Nkx2.5 and alpha-actinin

Treated with activin A and BMP-4

[58]

Skin

Epidermal cells

The presence of desmosomes; expressing CK18 and CK14

Cultured in air-liquid interface

[59]