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Table 1 A list of growth factors and small molecules adopted in the in vitro differentiation procedures

From: Recent progress in pancreatic islet cell therapy

Stages

Growth factors/small molecules

Signaling pathways

Functions

References

Rodent in vivo

Human in vitro

DE

Activin A

TGF-β superfamily member

Induce DE differentiation

[7, 8]

[9, 10]

Wnt3a

TGF-β superfamily

Induce mesendoderm differentiation

[11]

[12]

CHIR99021

GSK3β inhibitor (WNT)

Promote SOX17 expression better than Wnt3a

–

[13]

PG

FGF10

FGF signaling

Induce PG differentiation

[14, 15]

[12]

KAAD-cyclopamine

SHH inhibitor

Enhance DE differentiation

[6, 16]

[12]

KGF, FGF7

FGF signaling

Enhance PG and differentiation to the pancreatic lineage

[4, 17]

[18,19,20]

PP, EP

RA

RA signaling

Promote PDX1 expression

[4,5,6]

[10]

SANT1

SHH inhibitor

Enhance DE differentiation

[6, 16]

[18]

Noggin, LDN193189

BMP inhibitors

Enhance differentiation to the pancreatic lineage

[4]

[18,19,20,21,22]

ILV, PDBu, TPB

PKC activator

Promote PDX1 or NKX6.1 expression

–

[18, 19, 23]

EGF

EGF signaling

Enhance PP proliferation

[4, 24]

[22, 25, 26]

Sodium cromoglicate

BMP inhibitor

Promote NGN3 expression

–

[27]

EC

Alk5i

TGF-β receptor inhibitor

Induce differentiation to the endocrine lineage from PP

[4, 6]

[18]

Nicotinamide

Amide form of Vitamin B3

Induce EC differentiation

–

[10, 21, 22, 28]

N-acetyl cysteine

Antioxidant

Promote MAFA nuclear localization

[29]

[20]

T3

Thyroid hormone

Promote co-expression of NKX6.1 and INS

[30]

[19, 20]

γ-secretase inhibitor XX

Notch inhibitor

Enhance differentiation to the endocrine lineage

[31, 32]

[19, 30]

H1152

ROCK inhibitor

Promote INS expression

–

[33]

R428

AXL inhibitor

Promote MAFA production

–

[20]

  1. DE definitive endoderm; PG primitive gut tube; PP pancreatic progenitor; EP endocrine progenitor; EC endocrine cell; GSK3β glycogen synthase kinase 3 beta; FGF fibroblast growth factor; KAAD-cyclopamine 3-keto-N-(aminoethylaminocaproyl-dihydrocinnamoyl) cyclopamine; SHH sonic hedgehog; KGF keratinocyte growth factor; RA retinoic acid; BMP bone morphogenic protein; ILV Indolactom V; PDBu Phorbol 12, 13-Dibutyrate; TPB (2S,5S)-(E,E)-8-(5-(4-(trifluoromethyl)phenyl)-2,4-pentadienoylamino) benzolactam; PKC protein kinase C; EGF epidermal growth factor; Alk5i transforming growth factor beta receptor inhibitor; T3 thyroid hormone