Table 3.
Overview of skin models from induced pluripotent stem cells
| Source iPSC | Keratinocytes | Fibroblasts | Extra cell | Advantage/disadvantage | Ref. |
|---|---|---|---|---|---|
| Foreskin Fb; transfected with mRNA cocktail of c-MYC, SOX2, OCT4, KLF4, and LIN28 | Similar p63, ITGB4, K14 protein expression as neonatal KC | None | +: compared to primary healthy epidermal model; Permeability: TEER; Morphology: HE; DEJ: LAM; SB/ suprabasal: K14; Suprabasal: K10, INV; SG: FIL, TCHH, LCE2B; SC/SG: LOR; Cell-cell junction: DSC1 -: no dermal compartment (transwell), Fbs, immune cells, EC or appendages |
[55, 56] | |
| Foreskin Fb; retroviral transduction of c-MYC, SOX2, OCT4, KLF4, (Nanog*) | None iPSC derived (foreskin) (SE) or not used (DE) | Similar CD10, CD13, CDz44, CD73, CD90, CD166, COLI, COLII, PDGFRb expression as foreskin Fb COLIII, FN and tenascin C are different expressed |
+: compared to primary skin model; Morphology: HE; DEJ: COLIV +: collagen 1 matrix (SE)/ self-assembly approach (DE) -: KC not iPSC derived -: no immune cells, EC or appendages |
[51, 87] | |
| Foreskin Fb; retroviral transduction of reprogramming factors; SOX2, OCT3/4, KLF4 | Similar K5, K8, K14, K15, K19, INV, FIL, p63, ITGB4, ITGA6 and E-Cad expression as foreskin KC | ? | +: compared to primary skin model; Morphology: HE; SB/ suprabasal: cytokeratin, K14, K15 -: no clear methods construction skin model -: no immune cells, EC or appendages |
[65] | |
| Foreskin Fb; retroviral transduction of reprogramming factors; c-MYC, SOX2, OCT4, KLF4 | Similar p63, DSG3, ITGB4, lam5, K14 K5 and COLVII protein expression as foreskin KC |
Similar CD10, CD44, CD73, CD90, P4Hb, COLI, COLVII expression as foreskin Fb | MC: Similar SOX-10, MITF-M, gp-100 and melanin expression as foreskin MC | +: compared to primary healthy skin model Morphology: HE; DEJ: LAM5, COLVII; Suprabasal: K1; SC/SG: LOR +: functional iPSC-derived melanocytes +: type 1 collagen matrix -: no immune cells, EC or appendages |
[50, 57, 88] |
| Foreskin Fb; episomal transfection with L-MYC, SOX2, OCT3/4, KLF4 | None iPSC derived (foreskin) | None iPSC derived (foreskin) | EC: VE- cadherin and CD31 expression Formation of tube-like structures on matrigel |
+: compared to skin model with HUVEC Morphology: HE; Permeability endothelial barrier function; SB/ suprabasal: K14; Suprabasal: K10; SC/SG: LOR; EC: CD31 +: functional iPSC-derived EC +: type 1 collagen matrix -: KC and Fb are not iPSC derived -: no immune cells or appendages |
[58] |
*Nanog in combination with other reprogramming factors is used in one of two generated iPSC lines; COL collagen, DE dermal equivalent, DEJ dermal epidermal junction, DSC1 Desmocollin 1, DSG3 Desmoglein-3, EC endothelial cell, E-Cad E-cadherin, Fb fibroblasts, FIL filaggrin, FN fibronectin, gp-100 glycoprotein 100, HE Hematoxylin and eosin, HUVEC human umbilical vein endothelial cells, INV involucrin, iPSC induced pluripotent stem cell, ITGB4 Intergrin beta 4, ITGA6 Intergrin alpha 6, KC keratinocytes, K keratin, KLF4 Kruppel-like factors 4, LAM laminin, LCE2B late cornified envelope 2B, LOR loricrin MC melanocytes, MITF Microphthalmia-associated transcription factor, OCT4 Octamer binding transcription factor 4, PDGFRb, platelet-derived growth factor receptor-b, P4Hb Prolyl 4-Hydroxylase Subunit Beta, SB stratum basal, SC stratum corneum, SE skin equivalent, SG stratum granulosum, SS stratum spinosum, SOX2 SRY (sex determining region Y)-box 2, TCHH Trichohyalin, TEER transepithelial electric resistance, VE-cadherin vascular endothelial cadherin