Skip to main content

Advertisement

Log in

The capacity of goat epidermal adult stem cells to reconstruct the damaged ocular surface of total LSCD and activate corneal genetic programs

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Epidermal adult stem cells (EpiASCs) have the potential for unlimited proliferation and differentiation, however, the ability of these stem cells to activate corneal genetic programs in response to corneal stroma stimulation needs to be further validated. Herein, a feasible strategy was developed to reconstruct the damaged corneal surface in a goat model with total limbal stem cell deficiency (LSCD) by transplanting EpiASCs, which had been explanted and cultured from the skin of an adult ram goat and were then purified by selecting single cell-derived clones and cultivating them on a denuded human amniotic membrane (HAM). These artificial tissues were then successfully transplanted into ewe goats with total LSCD. Binding of EpiASCs to the base membrane of an EpiASCs-HAM-Sheet (EHS) indicated their proliferating status. After transplantation, the EpiASCs could survive in the host tissue and they reconstructed the damaged ocular surface of total LSCD. The crystal reconstructed corneal epithelium expressed CK3 and Pax-6 similar to normal corneal epithelium and expressed the Sry gene after transplantation. These results demonstrated that EpiASCs could be induced to differentiate into corneal epithelial cell types in a corneal microenvironment and had the ability to activate corneal genetic programs. This work offer a foundation for promoting tissue-engineered cornea into clinical application.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alina G, Monica P, Fildis M et al (2016) Ocular surface reconstruction in limbal stem cell deficiency. Rom J Ophthalmol 60(1):2–5

    PubMed Central  Google Scholar 

  • Bardag-Gorce F, Oliva J, Wood A et al (2015) Carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study. Ocul Surf 13(2):150–163

    PubMed  Google Scholar 

  • Blanpain C, Fuchs E (2014) Plasticity of epithelial stem cells in tissue regeneration. Science 344(6189):1242281

    PubMed  PubMed Central  Google Scholar 

  • Blazejewska EA, Schlotzer-Schrehardt U, Zenkel M et al (2009) Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells 27:642–652

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blazejewska EA, Call MK, Yamanaka O et al (2011) From hair to cornea: toward the therapeutic use of hair follicle-drived stem cells in the treatment of limbal stem cell deficiency. Stem Cells 29(1):57–66

    Google Scholar 

  • Davies EL, Lei K, Seidel CW et al (2017) Embryonic origin of adult stem cells required for tissue homeostasis and regeneration. Elife 6:e21052

    PubMed  PubMed Central  Google Scholar 

  • Dosh RH, Jordan-Mahy N, Sammon C et al (2019) Use of L-pNIPAM hydrogel as a 3D-scaffold for intestinal crypts and stem cell tissue engineering. Biomater Sci 7:4310–4324

    CAS  PubMed  Google Scholar 

  • Ezquer F, Ezquer M, Contador D et al (2012) The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment. Stem Cells 30(8):1664–1674

    CAS  PubMed  Google Scholar 

  • Ferraris C, Chevalier G, Favier B et al (2000) Adult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous and sweat gland genetic programs in response to embryonic dermal stimuli. Development 127:5487–5495

    CAS  PubMed  Google Scholar 

  • Figueiredo GS, Salvador-Culla B, Baylis OJ et al (2018) Outcomes of penetrating keratoplasty following autologous cultivated limbal epithelial stem cell transplantation: penetrating keratoplasty following CLET. Stem Cells 36(6):925–931

    CAS  PubMed  Google Scholar 

  • Fuchs E (2007) Scratching the surface of skin development. Nature 445(7130):834–842

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, Wu W, Ma X et al (2019) Comparative gene expression profiling reveals key pathways and genes different in skin epidermal stem cells and corneal epithelial cells. Genes Genom 41:679–688

    Google Scholar 

  • Huang M, Wang B, Wan P et al (2015) Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells. Cell Tissue Res 359(2):547–563

    CAS  PubMed  Google Scholar 

  • Le Q, Xu J, Deng SX (2017) The diagnosis of limbal stem cell deficiency. Ocul Surf 16(1):58–69

    PubMed  PubMed Central  Google Scholar 

  • Li W, He H, Kuo JL et al (2006) Basement membrane dissolution and re-assembly by limbal corneal epithelial cells expanded on amniotic membrane. Invest Ophthalmol Vis Sci 47(6):2381–2389

    PubMed  Google Scholar 

  • Li W, Hayashida Y, He H et al (2007) The fate of limbal epithelial progenitor cells during explant culture on intact amniotic membrane. Invest Ophthalmol Vis Sci 48(2):605–613

    PubMed  Google Scholar 

  • Linardi RL, Megee SO, Mainardi SR et al (2015) Expression and localization of epithelial stem cell and differentiation markers in equine skin, eye and hoof. Vet Dermatol 26(4):213–e47

    PubMed  PubMed Central  Google Scholar 

  • Marchini G, Pedrotti E, Pedrotti M et al (2012) Long-term effectiveness of autologous cultured limbal stem cell grafts in patients with limbal stem cell deficiency due to chemical burns. Clin Exp Ophthalmol 40(3):255–267

    PubMed  Google Scholar 

  • Pearton DJ, Yang Y, Dhouailly D (2005) Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals. PNAS 102(10):3714–3719

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qiao Q, Xu X, Song Y et al (2018) Semaphorin 3A promotes osteogenic differentiation of BMSC from type 2 diabetes mellitus rats. J Mol Histol 49(3):1–8

    Google Scholar 

  • Ramos T, Scott D, Ahmad S (2015) An update on ocular surface epithelial stem cells: cornea and conjunctiva. Stem Cells Int. https://doi.org/10.1155/2015/601731

    PubMed  PubMed Central  Google Scholar 

  • Schlotzer SU, Kruse FE (2005) Identification and characterization of limbal stem cells. Exp Eye Res 81:247–264

    Google Scholar 

  • Shahdadfar A, Haug K, Pathak M et al (2012) Ex vivo expanded autologous limbal epithelial cells on amniotic membrane using a culture medium with human serum as single supplement. Exp Eye Res 97(1):1–9

    CAS  PubMed  Google Scholar 

  • Shanbhag SS, Nikpoor N, Donthineni PR et al (2019) Autologous limbal stem cell transplantation: A systematic review of clinical outcomes with different surgical techniques. Brit J Opththalmol 104:247–253

    Google Scholar 

  • Shim JH, Kang HH, Lee TR et al (2012) Enrichment and characterization of human dermal stem/progenitor cells using collagen type IV. J Dermatol Sci 67(3):202–205

    CAS  PubMed  Google Scholar 

  • Shim JH, Lee TR, Shin DW (2013) Novel in vitro culture condition improves the stemness of human dermal stem/progenitor cells. Mol Cells 36(6):556–563

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor G, Lehrer MS, Jensen PJ et al (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461

    CAS  PubMed  Google Scholar 

  • Tsai RJ, Tsai RY (2014) From stem cell niche environments to engineering of corneal epithelium tissue. Jpn J Ophthalmol 58(2):111–119

    CAS  PubMed  Google Scholar 

  • Watson S, Sarris M, Kuishek M et al (2013) Limbal dermoid epithelium shares phenotypic characteristics common to both hair epidermal and limbal epithelial stem cells. Curr Eye Res 38(8):835–842

    CAS  PubMed  Google Scholar 

  • Yang X, Lei Qu, Wang X et al (2007) Plasticity of epidermal adult stem cells derived from adult goat ear skin stem cells. Mole Reprod Dev 74(3):386–396

    CAS  Google Scholar 

  • Yang X, Moldovan N, Zhao Q et al (2008) Reconstruction of damaged corneas by transplantation of epidermal adult stem cells. Mol Vis 14:1064–1070

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang RH, Xie JL, Shu B et al (2013) An improved method for the isolation and culture of rat epidermal stem cells. Int J Clin Exp Pathol 6(11):2529–2534

    PubMed  PubMed Central  Google Scholar 

  • Yoon JJ, Ismail S, Sherwin T (2014) Limbal stem cells: Central concepts of corneal epithelial homeostasis. World J Stem Cells 6(4):391–403

    PubMed  PubMed Central  Google Scholar 

  • Zhang C, Du L, Pang K et al (2017) Differentiation of human embryonic stem cells into corneal epithelial progenitor cells under defined conditions. PLoS ONE 12(8):e0183303

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was financially supported by a grant of National Natural Science Foundation of China (No. 31240089), National Natural Science Foundation of China (No. 31701121), Henan Province Science and Technology Research Project (No. 182102310667), Key Projects of Universities in Henan Province (No. 180211316170). This study was supported by Northwest A & F University. We are grateful to Professor Zhongying Dou, Jinlian Hua, Huayan Wang, Anming Lei and Yongjiang Ma.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xue-yi Yang.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, P., Ma, Xy., Huang, Dt. et al. The capacity of goat epidermal adult stem cells to reconstruct the damaged ocular surface of total LSCD and activate corneal genetic programs. J Mol Hist 51, 277–286 (2020). https://doi.org/10.1007/s10735-020-09879-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-020-09879-4

Keywords

Navigation