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Limbusstammzelltransplantation

Aktueller Stand und Perspektiven

Limbal epithelial stem cell transplantation

Current state and perspectives

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Zusammenfassung

Die Homöostase der Hornhautoberfläche wird durch die im Limbus lokalisierten epithelialen Stammzellen reguliert. Multiple intrinsische Faktoren oder externe Verletzungen können die empfindliche Mikroumgebung der Stammzellen zerstören, sodass eine limbale Stammzellinsuffizienz entsteht. In solchen Fällen versagt die Reepithelialisierung der Hornhaut, und konjunktivales Epithel erstreckt sich über den Limbus auf die Hornhautoberfläche. Bei einer partiellen limbalen Stammzellinsuffizienz (LSZI) kann eine oberflächliche Keratektomie kombiniert mit einer Amnionmembrantransplantation ausreichend sein, um eine intakte, gesunde Augenoberfläche wiederherzustellen. In schwereren Fällen mit kompletter LSZI ist die Stammzelltransplantation derzeit die einzige kurative Option. Vor jeder Rekonstruktion mittels Stammzelltransplantation sollten ursächliche Faktoren und Komorbiditäten behandelt werden. In Fällen von einseitiger LSZI können Stammzellen aus dem kontralateralen Auge gewonnen werden. Neuere Operations- und Kultivierungstechniken verfolgen hierbei das Ziel, möglichst gewebeschonend am gesunden, einzig funktionstüchtigen Auge vorzugehen. Die teilweise bereits gut etablierten In-vitro- und In-vivo-Methoden verringern somit die Notwendigkeit, große Limbusbiopsate zu gewinnen. Patienten mit bilateraler Beteiligung können mit allogenem Gewebe versorgt werden, benötigen aber in diesem Fall eine längerfristige, systemische immunsuppressive Therapie. Eine weitere, neuere Möglichkeit ist die Verwendung von autologen, aber nichtkornealen Epithelzellen als Gewebequelle, wie z. B. Mundschleimhaut. Zukünftige Studien setzen ihre Schwerpunkte in der Weiterentwicklung der zellulären Expansion und/oder der Etablierung und Suche von neuen, alternativen Quellen für limbale Stammzellen.

Abstract

Homeostasis of the corneal surface is maintained by epithelial stem cells localized in the limbus. Multiple intrinsic factors or external injuries can destroy the delicate microenvironment of limbal epithelial stem cells causing a state which is termed limbal stem cell deficiency (LSCD). In such cases, re-epithelialization of the cornea is drastically impeded and conjunctival epithelium starts to extend beyond the limbus and to invade the corneal surface. In partial LSCD, a superficial keratectomy combined with an amniotic membrane is advised and helpful to restore an intact, healthy ocular surface. In complete LSCD, stem cell transplantation is the only curative option. Before any reconstruction, causative factors and comorbidities should be eliminated or at least optimized. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Advanced surgical and cultivation techniques pursue a gentle, tissue-saving procedure of harvesting a limbal biopsy from the only healthy functioning eye. Patients with bilateral involvement can be treated with allogeneic tissue, but will require long-term systemic immunosuppressive therapy. Another newer option is the use of autologous, but noncorneal epithelial cells as a tissue source, e.g., buccal mucosa. Future studies will focus on the further development of cellular expansion and/or the establishment of new alternative sources for replacing limbal epithelial stem cells.

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Literatur

  1. Amescua G, Atallah M, Nikpoor N et al (2014) Modified simple limbal epithelial transplantation using cryopreserved amniotic membrane for unilateral limbal stem cell deficiency. Am J Ophthalmol 158:469–475

    Article  CAS  PubMed  Google Scholar 

  2. Bakker A, Langer B (2015) Zelltherapeutika – eine innovative Therapieoption in der Ophthalmologie. Bundesgesundheitsblatt 58:1259–1264

    Article  Google Scholar 

  3. Basu S, Sureka SP, Shanbhag SS et al (2016) Simple limbal epithelial transplantation: long-term clinical outcomes in 125 cases of unilateral chronic ocular surface burns. Ophthalmology 123:1000–1010

    Article  PubMed  Google Scholar 

  4. Cotsarelis G, Cheng SZ, Dong G et al (1989) Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell 57:201–209

    Article  CAS  PubMed  Google Scholar 

  5. Dua HS, Saini JS, Azuara-Blanco A et al (2000) Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol 48:83–92

    CAS  PubMed  Google Scholar 

  6. Hernández-Bogantes E, Amescua G, Navas A et al (2015) Minor ipsilateral simple limbal epithelial transplantation (mini-SLET) for pterygium treatment. Br J Ophthalmol 99:1598–1600

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kaliki S, Mohammad FA, Tahiliani P et al (2016) Concomitant simple limbal epithelial transplantation after surgical excision of ocular surface squamous neoplasia. Am J Ophthalmol 174:68. doi:10.1016/j.ajo.2016.10.021

    Article  PubMed  Google Scholar 

  8. Kolli S, Ahmad S, Singh Mudhar H et al (2014) Succesful application of ex vivo expanded human autologous oral epithelium for the treatment of bilateral limbal stem cell deficiency. Stem Cells 32:2135–2146

    Article  CAS  PubMed  Google Scholar 

  9. Ksander BR, Kolovou PE, Wilson BJ et al (2014) ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature 511:353–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ma DH, Kuo MT, Tsai YJ et al (2009) Transplantation of cultivated oral mucosal epithelialcells for severe corneal burn. Eye (Lond) 23:1442–1450

    Article  CAS  Google Scholar 

  11. Meller D, Pires RT, Tseng SC (2002) Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures. Br J Ophthalmol 86:463–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Meller, D., Pauklin, M., Westekemper, H. et al. (2010) Autologe Transplantation von kultiviertem Limbusepithel. Ophthalmologe 107:1133–1138.

  13. Meller D, Thomasen H, Hanet M et al (2013) Kurz- und Langzeitkomplikationen nach Transplantation von kultiviertem Limbusepithel. Ophthalmologe 110:622–628

    Article  CAS  PubMed  Google Scholar 

  14. Miri A, Al-Deiri B, Dua HS (2010) Long-term outcomes of autolimbal and allolimbal transplants. Ophthalmology 117:1207–1213

    Article  PubMed  Google Scholar 

  15. Mittal V, Jain R, Mittal R (2015) Ocular surface epithelialization pattern after simple limbal epithelial transplantation: an in vivo observational study. Cornea 34:1227–1232

    Article  PubMed  Google Scholar 

  16. Mittal V, Narang P, Menon V et al (2016) Primary simple limbal epithelial transplantation along with excisional biopsy in the management of extensive ocular surface squamous neoplasia. Cornea 35:1650. doi:10.1097/ico.0000000000000953

    Article  PubMed  Google Scholar 

  17. Nishida K, Yamato M, Hayashida Y et al (2004) Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med 351:1187–1196

    Article  CAS  PubMed  Google Scholar 

  18. Nakamura T, Inatomi T, Sotozono C et al (2004) Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol 88:1280–1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nakamura T, Takeda K, Inatomi T et al (2011) Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol 95:942–946

    Article  PubMed  Google Scholar 

  20. Pauklin M, Steuhl KP, Meller D (2009) Characterization of the corneal surface in limbal stem cell deficiency and after transplantation of cultivated limbal epithelium. Ophthalmology 116:1048–1056

    Article  PubMed  Google Scholar 

  21. Pauklin M, Fuchsluger TA, Westekemper H et al (2010) Midterm results of cultivated autologous and allogeneic limbal epithelial transplantation in limbal stem cell deficiency. Dev Ophthalmol 45:57–70

    Article  PubMed  Google Scholar 

  22. Pellegrini G, Traverso CE, Franzi AT et al (1997) Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet 349:990–993

    Article  CAS  PubMed  Google Scholar 

  23. Puangsricharern V, Tseng SCG (1995) Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology 102:1476–1485

    Article  CAS  PubMed  Google Scholar 

  24. Rama P, Matuska S, Paganoni G (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363:147–155

    Article  CAS  PubMed  Google Scholar 

  25. Rohaina CM, Then KY, Ng AMH et al (2014) Reconstruction of limbal stem cell deficient corneal surface with induced human bone marrow mesenchymal stem cells on amniotic membrane. Transl Res 163:200–210

    Article  CAS  PubMed  Google Scholar 

  26. Sangwan VS, Basu S, MacNeil S et al (2012) Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol 96:931–934

    Article  PubMed  Google Scholar 

  27. Satake Y, Higa K, Tsubota K et al (2011) Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology 118:1524–1530

    Article  PubMed  Google Scholar 

  28. Schermer A, Galvin S, Sun TT (1986) Differentiation-related expression of a major 64 K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol 103:49–62

    Article  CAS  PubMed  Google Scholar 

  29. Scholz S, Thomasen H, Hestermann K et al (2016) Langzeitergebnisse zur autologen Transplantation von ex vivo kultiviertem Limbusepithel bei limbaler Stammzellinsuffizienz. Ophthalmologe 113:321–329

    Article  CAS  PubMed  Google Scholar 

  30. Sun TT, Tseng SC, Lavker RM (2010) Location of corneal epithelial stem cells. Nature 25:463

    Google Scholar 

  31. Tsai RJ, Li LM, Chen JK (2000) Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med 343:86–93

    Article  CAS  PubMed  Google Scholar 

  32. Tseng SC (1989) Concept and application of limbal stem cells. Eye (Lond) 3:141–157

    Article  Google Scholar 

  33. Vazirani J, Ali MH, Sharma N et al (2016) Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicentre results. Br J Ophthalmol 100:1416–1420

    Article  PubMed  Google Scholar 

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Correspondence to D. Meller FEBO.

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Interessenkonflikt

D. Meller und H. Thomasen geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Herrn Professor Klaus-Peter Steuhl, Klinik für Erkrankungen des vorderen Augenabschnitts, Zentrum für Augenheilkunde, Universität Duisburg-Essen, zur Emeritierung gewidmet.

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Meller, D., Thomasen, H. Limbusstammzelltransplantation. Ophthalmologe 114, 298–306 (2017). https://doi.org/10.1007/s00347-017-0462-6

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