Pancreatic Progenitors and Organoids as a Prerequisite to Model Pancreatic Diseases and Cancer
Table 1
Comparison of in vitro pancreatic endocrine differentiation protocols.
Kieffer (Rezania et al.)
Melton (Pagliuca et al.)
Hebrok (Russ et al.)
Culture system
Monolayer followed by air-liquid interphase
Suspension in spinner flasks
Suspension on orbital shaker
Cell lines
H1, iPSC line
HUES8, 2 iPSC lines
Mel1 InsGFP/W
Divergent conditions
Vitamin C from PGT stage to PE stage; protein kinase C (PKC) activator TPB after the PGT and PFG stages; SHH/BMP inhibition after the PGT stage; thyroid hormone, heparin, and EGFR ligand after the PE stage; vitamin E analog, AXL inhibitor, and N-Cys at the β-cell stage; total 27-43 days
Media change every other day after d2; PKC activator PdBU after the PGT stage; Notch inhibition and EGF signaling after the PP2 stage; total 27-34 days
TGFβ-inhibitor after the DE stage; RA analog only in high glucose medium after the GT stage; EGF after the PP1 stage; BMP inhibition and FGF signaling after the PP2 stage; no growth factors after the EP stage; shortened time intervals (total 21 days)
Efficiency PP
70% NKX6.1+/PDX1+ (PP), 76% (immature β-cells)
>55% NKX6.1+/PDX1+ (PP2)
80% NKX6.1+/PDX1+ (d9)
Efficiency beta cells
40% PDX1+/INS+ (maturing β-cells)
33% PDX1+/C-peptide+ (functional β-cells)
25% PDX1+/C-peptide+ (β-like cells)
In vivo transplantation (mouse)
Human C-peptide within 2 weeks after transplantation, ameliorates hyperglycemia after d40 posttransplantation
Human C-peptide within 2 weeks after transplantation, ameliorates progressive hyperglycemia
Human C-peptide within 7-10d after transplantation, reduces STZ-induced hyperglycemia
