Table 3.
Differentiation of expanded organoids from adult murine and human pancreata
| Cell source | In vitro differentiation | In vivo differentiation | Maturation by histology | C-peptide secretion | Reference no. |
|---|---|---|---|---|---|
| Mouse, EpCAM+ TSQ− CAG+ | - | Re-aggregated with embryonic cells, transplanted under kidney capsule | 2.5% insulin+ (all mono-hormonal) | In mice: detectable, response not tested | 46 |
| Mouse, hand-picked single ducts | Lentiviral delivery: Pdx1, MafA, Ngn3-WT | - | 7% insulin+ | - | 49 |
| Lentiviral delivery: Pdx1, MafA, Ngn3-phosphomutant | - | 28% insulin+ (33% coexpressed somatostatin) | - | ||
| Plus medium modification: ROCK inhibitor; IWP-2, w/o R-Spondin-1, EGF for the last 2 days | - | 61% insulin+ (41% coexpressed somatostatin) | - | ||
| Plus last 2 days the three genes turned off | - | 61% insulin+ (87% mono-hormonal) | - | ||
| Human, islet-depleted fragments | Nicotinamide containing medium | Transplanted under kidney capsule in normoglycemic or hyperglycemic mice | 1.5% insulin+ (mono-hormonal) | In mice: detectable, not glucose-responsive | 47 |
| Human, CD133+ | Adenoviral delivery: PDX1, MAFA, NGN3, PAX6; Medium: Retinoic acid; w/o R-spondin | Transplanted under kidney capsule | 7–11% insulin+ (all mono-hormonal) | In vitro: not glucose-responsive; In mice: detectable* | 53 |
| Human, CD133+ | mRNA delivery: NGN3; Medium: RepSox, PP2, ISX-9, GSK126, 5-aza-2´-deoxycytidin, Forskolin | - | 5% insulin+ (some coexpressed somatostatin) | In vitro: not glucose-responsive | 52 |
| Mouse, Procr+ cells from islets | B27, ITS, EGF, FGF2, heparin, endothelial cells | Organoid transplanted under the kidney capsule were already differentiated | in vitro: 30% mono-hormonal insulin+cells, 70% bi-hormonal insulin+ cells | In vitro: glucose-responsive, In mice: glucose-responsive | 161 |
| *After 3 g/kg of glucose, after o/n starving, there was a trend to incresed C-peptide levels, but statistical significance is not reported. | |||||