Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration
Abstract
:1. Introduction
2. Corneal Epithelial Cell
3. Signaling Pathways Related to Corneal Epithelial Differentiation
4. Corneal Epithelial Differentiation of Human MSCs
5. Corneal Epithelial Differentiation of Human PSCs
6. Future Perspective
Author Contributions
Funding
Conflicts of Interest
References
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Human MSCs | Signal Providing Cells | Culture Medium | Duration (Days) | Marker Expression at the Final Differentiation Stage | Reference |
---|---|---|---|---|---|
AT-MSCs | porcine limbal epithelial stem cells | DMEM FBS 10% | 14 | gene expression increase: CK3, CK12, p63 decrease: CD73, CD90, CD105, CK15, CK19, Cx43, ABCG2 | [119] |
CJ-MSCs | human corneal epithelial cells | SHEM medium FBS 5% DMSO 0.5% EGF 5 ng/mL Insulin 5 μg/mL Transferrin 5 μg/mL Sodium selenite 5 ng/mL Hydrocortisone 0.5 μg/mL Cholera toxin A 30 ng/mL | 24 | gene expression increase: CK3, CK8, CK12, CK14, CK15, ABCG2, DSC1, DSG1, NP63-α, Nestin, Involucrin ICC positive: CK3 | [24] |
EDT-MSCs | human corneal epithelial cells | DMEM/Ham F12 (1:1) FBS 5% DMSO 0.5% EGF 5 ng/mL | 21 | gene expression increase: CK3, CK19 ICC positive: CK3, CK19 | [120] |
Human MSCs | Induction Medium | Duration (Days) | Marker Expression at the Final Differentiation Stage | Reference |
---|---|---|---|---|
CJ-MSCs | CnT-Prime 3D medium | 24 | gene expression increase: CK3, CK8, CK12, CK14, CK15, ABCG2, DSC1, DSG1, NP63-α, Nestin, Involucrin ICC positive: CK3 | [24] |
CJ-MSCs | DMEM: Ham’s F-12 (3:1) FBS 5% EGF 10 ng/mL Insulin 5 μg/mL Hydrocortisone 0.5 μg/mL Triiodothyronine 2 nM Adenine 2 nM | 21 | gene expression increase: CK3, CK8, CK12, DSC1, DSG1 | [121] |
BM-MSCs | Step 1 DMEM EGF 10 ng/mL BMP4 25 ng/mL All-trans retinoic acid 1 μM Step 2 DMEM: Ham’s F-12 (3:1) FBS 5% EGF 10 ng/mL Insulin 5 μg/mL Hydrocortisone 0.5 μg/mL Triiodothyronine 2 nM Adenine 2 nM | 4 (step 1) and 12 (step 2) | gene expression increase: CK3, CK8, CK12, DSC1, DSG1 decrease: Oct4, Sox2, Nanog, Rex1, p63, ABCG2 ICC positive: CK3, CK8, CK12, CK14, CK15, β-integrin, E-cadherin negative: α-SMA | [20] |
BM-MSCs | DMEM FBS 2% L-glutamine 2 mM All-trans retinoic acid 1 μM | 7 | gene expression increase: CK3, CK12, CK19, E-cad, ITGB1, Wnt-2, Snail decrease: Vimentin Protein expression increase: CK12, CK19, ITGB1, N-cad decrease: CK3, Vimentin, Snail, α-sma | [21] |
BM-MSCs | SHEM/Ham’s F12 (2:1) FBS 2% DMSO 0.5% L-Glutamine 2 mM EGF 10 ng/mL Insulin 5 μg/mL Hydrocortisone 0.4 μg/mL Triiodothyronine 2 nM Adenine 0.18 mM | 7 | gene expression increase: CK3, CK12, ITGB1 decrease: CK19, E-cad, Vimentin, Wnt-2, Snail Protein expression increase: CK3, CK12, ITGB1 decrease: CK19, Vimentin, Snail, α-sma, N-cad | [21] |
Human Cell Line | Method | Step 1 | Step 2 | Step 3 | Duration (Days) | ICC Result | Flow Cytometry/Cytospin Result | Gene Expression Result | Reference |
---|---|---|---|---|---|---|---|---|---|
ESCs (H1, hES-NCL1) | CM of MMC-treated limbal fibroblasts | 3LG-DMEM/1F12 +hydrocortisone, insulin, adenine, EGF, tri-iodothyronine, cholera toxin | - | 21 | hES-NCL1: high positive with CK12, CK3/12, p63 on D7 | Flow cytometry p63 highest on D6 hES-NCL1: CK3/12~55% highest on D6 H1: CK3/12~55% highest on D9 | CK3 highest on D15 hES-NCL1: CK3+, CK12+ highest on D6 H1: CK3+++, CK12+++ highest on D9 | [25] | |
iPSCs (L1B41, L1C51, 253G1, 201B7, L1B34) | Co-culture with MMC-treated PA6 | GMEM +KSR, 2-mercaptoethanol | 12–16 weeks | L1B41: CK12, CK3, PAX6, CK14 | L1B41 high responsive: CK3, CK12: high express from week 8–12 Other cell lines low or non-responsive | [137] | |||
ESCs (H9, H3, H14) iPSCs (6-9-9, 19-9-11) | Defined medium | DMEM/F12 +β-mercaptoethanol, DMSO, SU6656 | DMEM/F12 +RA, BMP4, bFGF, β-mercaptoethanol | DKSFM | 19 | CK14, CK3, p63 | Flow cytometry CK3 5%, CK14 90.7% | [59] | |
iPSCs | Defined medium | RegES medium +SB505124, IWP-2, bFGF | Cnt-30 | 44 | D20 CK12, CK3, CK15, Ki67, Pax6 | Cytospin on D44 p63 70%, CK3 30%, CK15 55%, CK12 70% | P63+++, CK15++, CK3+, and CK12+ | [61] | |
ESCs (H9, RCM1) | CM from limbal fibroblasts | 3LG-DMEM/1F12 +hydrocortisone, insulin, adenine, EGF, triiodothyronine, cholera toxin | 21 | - | Flow cytometry H9: CK3 99% on D21, high rate from D4–21 RCM1: CK12 94% on D21, high rate from D16–21 | CK3, CK12: very low express, p63, CK19, ABCG2: high express on D16 and D21 | [130] | ||
iPSCs | CM from limbal stromal cells | EpiLife medium +human corneal growth supplement | 21 | CK3, CK12, p63 express from D7–21 | CK3, CK12 high express on D14–21 | [131] | |||
iPSCs (UTA.045111.WT) | Defined medium | XF-Ko-SR D1: blebbistatin D2: SB505124, bFGF D3–4: BMP4 | Cnt-30 | 21 | CK14, CK15, p63, PAX6 | Flow cytometry p63 71% | [85] | ||
ESCs (H9) iPSCs (SBAd2, SBAd3) | Defined medium | mTeSR1 D1:Y27632 | DMEM/F12 +BMP4/RA/EGF/LDN193189 or BMP4+RA+EGF or SB505124+IWP2 w/wo BMP4 | CnT prime +10%FBS | 20 | CK12: not different on D20, CK3: lower express on D20 in SBAd3 group | BMP4+RA+EGF is the best SBAd2 &H9 responsive: CK3, CK12: high express SBAd3 non-responsive | [83] | |
ESCs (H1, H9, CT3, Envy (GFP+)) | Defined medium | E6 +IWR1, A83-01, bFGF w/wo BMP4 | E6 | 75 | CK12, CK3 | Flow cytometry CK3 55.6%, CK12 28.2% | [76] | ||
ESCs (Regea 08/017, Regea11/013) iPSCs (UTA.04607.WT) | Defined medium | XF-Ko-SR D1: blebbistatin D2: SB505124, bFGF D3–4: BMP4 | Cnt-30 | 24 | D11: ABCG2+++, ∆Np63++, LGR5+++ D24: ABCG2+, ∆Np63+++, LGR5+, CK14+++, CK15++ | Cytopsin: D11: ABCG2 62.4%, ∆Np63 23.2%, CD200 42.6% D24: ABCG2 1.8%, ∆Np63 54.3%, CK15 37%, CK14 56.2% | [87] |
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Theerakittayakorn, K.; Thi Nguyen, H.; Musika, J.; Kunkanjanawan, H.; Imsoonthornruksa, S.; Somredngan, S.; Ketudat-Cairns, M.; Parnpai, R. Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration. Int. J. Mol. Sci. 2020, 21, 7834. https://doi.org/10.3390/ijms21217834
Theerakittayakorn K, Thi Nguyen H, Musika J, Kunkanjanawan H, Imsoonthornruksa S, Somredngan S, Ketudat-Cairns M, Parnpai R. Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration. International Journal of Molecular Sciences. 2020; 21(21):7834. https://doi.org/10.3390/ijms21217834
Chicago/Turabian StyleTheerakittayakorn, Kasem, Hong Thi Nguyen, Jidapa Musika, Hataiwan Kunkanjanawan, Sumeth Imsoonthornruksa, Sirilak Somredngan, Mariena Ketudat-Cairns, and Rangsun Parnpai. 2020. "Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration" International Journal of Molecular Sciences 21, no. 21: 7834. https://doi.org/10.3390/ijms21217834