Table 1.
Overview of small molecules involved in the development process and showing the functionality of β-like cell-derived from various sources of stem cells.
| Stem Cell Source | Protocol | DE Markers (%) |
PE Markers PDX+ (%) |
PPs Markers (%) | Insulin Producing Cell INS+/C- Peptide+/GCG+ (%) | In vivo Efficacy: Glucose Homeostasis Restoration |
GSIS | References |
|---|---|---|---|---|---|---|---|---|
| hESCs | Day 1–2: Activin A+WNT3A. Day 3–5: TGF-βi+KGF. Day 6–8: Noggin+RA+Cyclopamine. Day 9–10: EGF+KGF+Noggin. Day 11–20: TBP+ALKi+Noggin | NA | > 88% PDX1+ | 80% NKX6.1+/PDX1+ | 92% NKX6.1+/C-peptide+ | √ | In vitro √; In vivo √ | [15] |
| hESCs, hiPSCs | Day 1: Activin A+CHIR. Day 2: Activin A. Day 4–6: KGF. Day 7–8: KGF+SANT1+RA+LDN+PdBU. Days 9–13: KGF+SANT1 +RA. Day 14–16: SANT1+RA+XXI+ ALK5iII+T3+Betacellulin. Day 18–20: RA+ XXI+ALK5iII+T3+Betacellulin. Day 21–35: ALK5iII+T3 | >95% SOX17+ | >85% PDX1+ | >55% NKX6.1+/PDX1+ | 8% C-peptide+/GCG+ | √ | In vitro √; In vivo √ | [17] |
| hiPSCs | Day 1–3: Activin A+CHIR+WNT3A. Day 4–10: Noggin+Dorsomorphin+RA+SB431542. Day 11–21: Forskolin+Dexamethasone+ALK5iII+Nicotinamid. | 75% SOX17+/ FOXA2+ | NA | 72% PDX1+ | 8–16% INS+ | NA | In vitro √ | [19] |
| hESCs | Day 1: Activin A+Li+CHIR. Day 2–5: Activin A. Day 6–11: RA+Dorsomorphin+SB431542+KAAD-Cyclopamine+FGF2. Day 12–15: DAPT+Dorsomorphin+SB431542 +Ascorbic acid. Day 16–23: Db-cAMP+Exendin-4+Dorsomorphin+SB431542+Nicotinamide+Ascorbic acid | >94% CXCR4+ | 93% PDX1+ | NA | NA | √ | In vitro √; In vivo √ | [22] |
| hESCs | Day 1–3: GDF8+GSK3-βi. Day 4–5: FGF7+VitC. Day 6–10: FGF7+VitC+RA+ SANT+TPB+LDN. Day 11–13: SANT+RA+ ALK5iII+T3+LDN. Day 14–28: ALK5iII +T3+LDN+GSiXX. Days 28–43: ALK5iII +T3+N-Cys+AXLi. | NA | NA | 76% | 31–38% NKX6.1+/INS+ 21% NKX6.1+/GCG+ | √ | In vivo √ | [23] |
| hiPSCs | Day 1–2: CHIR+FGF2+Activin-A+BMP4. Day 3–5: FGF2+Activin-A+BMP4. Day 6–7: FGF2+FGF7+EC23+SB431542+Dorsomorhin+SANT1. Day 8–11: FGF2+EC23+SB431542+ Dorsomorphin+SANT1. Day 12–14: FGF10 +EC23 +Dorsomorphin+SANT1+ALK5iII +ILV. Day 15–17: EC23+Dorsomorphin +SANT1+ALK5iII+Exendin-4. Day 18–23: BMP4+FGF2+HGF+IGF+Nicotinamide+Forskolin+Exendin-4+ALK5iII | >80% SOX17+; >68% FOXA2+ | 92% PDX1+ | NA | 34% C-peptide+ | √ | In vitro √; In vivo √ | [24] |
| hiPSCs | Day 1–3: Activin-A+CHIR. Day 4–6: KGF. Day 7–8: KGF+RA+SANT1+Y27632+LDN+PdbU. Day 9–13: KGF+RA+SANT1 +Y27632+Activin A. Day 14–20: RA+SANT1+T3+XXI+ALK5i+Heparin+Betacellulin. Day 21–34: T3+ALK5i+ CMRL supplemented | NA | NA | 52-89% NKX6.1+/PDX1+ | 30% NKX6.1+/C-peptide+ | √ | In vitro √; In vivo √ | [43] |
| BM-MSCs | Day 1–2: β-ME. Day 3–10: NEAA+bFGF+EGF+2% B27+L-glutamine. Day 11–18: Betacellulin+Activin-A+2% B27+Nicotinamide. | NA | NA | NA | 5–10% INS+/C- peptide+ | √ | In vitro √; In vivo √ | [44] |
| ASCs | Day 1–3: Activin-A+Sodium butyrate+ITS+β-ME. Day 4–5: Taurine+ITS. Day 6–10: Taurine+ITS+Nicotinamide+NEAA+GLP-1. | 28% SOX17+; 22% FOXA2+ | 65% PDX1+ | 48% C-peptide+ | √ | In vitro √; In vivo √ | [45] | |
| hMSCs | Day 1–7: Nicotinamide. Day 8–14: Exendin-4 | NA | NA | NA | 15% INS+ 6% C-peptide+ | √ | In vitro √; In vivo √ | [46] |
√ (Yes): Indicates the efficiency of differentiated cells towards Glucose Homeostasis Restoration and GSIS.