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Comparison of the efficacy of different cell sources for transplantation in total limbal stem cell deficiency

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Abstract

Purpose

The purpose of this study was to compare the efficacy of allogeneic cultured limbal epithelial transplantation (ACLET) and cultivated oral mucosal epithelial transplantation (COMET) in treating total limbal stem cell deficiency (LSCD).

Methods

In this retrospective cohort study, 73 patients (76 eyes) with total LSCD, including 41 patients (42 eyes) treated with ACLET and 32 patients (34 eyes) receiving COMET, were evaluated. The age, gender and injury cause of all patients were recorded.

Results

The mean follow-up was 23.3 ± 9.9 months in the ACLET group and 16.1 ± 5.8 months in the COMET group. A higher incidence of persistent epithelial defect was observed after COMET (P = 0.023). The overall ocular surface grading scores were all lower in the ACLET group than in the COMET group at 3, 6, and 12 months after surgery and the last follow-up. Kaplan-Meier survival curve analysis demonstrated a significantly higher success rate of ACLET (71.4%), compared with that of COMET (52.9%; P = 0.043). The risk of graft failure was higher in patients with entropion and trichiasis, incomplete eyelid closure and treated with COMET. The graft failure risk rate after COMET was 3.5 times higher than that of ACLET.

Conclusions

For total LSCD patients, ACLET should be prioritized, since limbal epithelial cells have better ability to maintain corneal epithelial integrity and ocular surface stability and benefit the ocular surface when compared with oral mucosal epithelial cells. Preoperative and postoperative eyelid abnormalities should be corrected as early as possible.

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References

  1. Kinoshita S, Adachi W, Sotozono C, Nishida K, Yokoi N, Quantock AJ, Okubo K (2001) Characteristics of the human ocular surface epithelium. Prog Retin Eye Res 20:639–673

    Article  CAS  PubMed  Google Scholar 

  2. Avunduk AM, Tekelioglu Y (2006) Therapeutic use of limbal stem cells. Curr Stem Cell Res Ther 1:231–238

    Article  CAS  PubMed  Google Scholar 

  3. Kawasaki S, Nishida K, Sotozono C, Quantock AJ, Kinoshita S (2000) Conjunctival inflammation in the chronic phase of Stevens-Johnson syndrome. Br J Ophthalmol 84:1191–1193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wall V, Yen MT, Yang MC, Huang AJ, Pflugfelder SC (2003) Management of the late ocular sequelae of Stevens-Johnson syndrome. Ocul Surf 1:192–201

    Article  PubMed  Google Scholar 

  5. Utheim TP (2013) Limbal epithelial cell therapy: past, present, and future. Methods Mol Biol 1014:3–43

    Article  CAS  PubMed  Google Scholar 

  6. Koizumi N, Inatomi T, Suzuki T, Sotozono C, Kinoshita S (2001) Cultivated corneal epithelial stem cell transplantation in ocular surface disorders. Ophthalmology 108:1569–1574

    Article  CAS  PubMed  Google Scholar 

  7. Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S (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 

  8. Shortt AJ, Secker GA, Notara MD, Limb GA, Khaw PT, Tuft SJ, Daniels JT (2007) Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol 52:483–502

    Article  PubMed  Google Scholar 

  9. Shortt AJ, Tuft SJ, Daniels JT (2010) Ex vivo cultured limbal epithelial transplantation. A clinical perspective. Ocul Surf 8:80–90

    Article  PubMed  Google Scholar 

  10. Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S (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 

  11. Subramaniam SV, Sejpal K, Fatima A, Gaddipati S, Vemuganti GK, Sangwan VS (2013) Coculture of autologous limbal and conjunctival epithelial cells to treat severe ocular surface disorders: long-term survival analysis. Indian J Ophthalmol 61:202–207

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kolli S, Ahmad S, Mudhar HS, Meeny A, Lako M, Figueiredo FC (2014) Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. Stem Cells 32:2135–2146

    Article  CAS  PubMed  Google Scholar 

  13. Satake Y, Yamaguchi T, Hirayama M, Higa K, Shimazaki-Den S, Dogru M, Kawakita T, Kawashima M, Shimmura S, Tsubota K, Shimazaki J (2014) Ocular surface reconstruction by cultivated epithelial sheet transplantation. Cornea 33(Suppl 11):S42–S46

    Article  PubMed  Google Scholar 

  14. Utheim TP (2015) Concise review: transplantation of cultured oral mucosal epithelial cells for treating limbal stem cell deficiency-current status and future perspectives. Stem Cells 33:1685–1695

    Article  CAS  PubMed  Google Scholar 

  15. Zhao Y, Ma L (2015) Systematic review and meta-analysis on transplantation of ex vivo cultivated limbal epithelial stem cell on amniotic membrane in limbal stem cell deficiency. Cornea 34:592–600

    Article  PubMed  Google Scholar 

  16. Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, Tano Y (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 

  17. Shimazaki J, Shimmura S, Tsubota K (2004) Donor source affects the outcome of ocular surface reconstruction in chemical or thermal burns of the cornea. Ophthalmology 111:38–44

    Article  PubMed  Google Scholar 

  18. Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363:147–155

    Article  CAS  Google Scholar 

  19. Dhamodaran K, Subramani M, Jeyabalan N, Ponnalagu M, Chevour P, Shetty R, Matalia H, Shetty R, Prince SE, Das D (2015) Characterization of ex vivo cultured limbal, conjunctival, and oral mucosal cells: a comparative study with implications in transplantation medicine. Mol Vis 21:828–845

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Krishnan S, Iyer GK, Krishnakumar S (2010) Culture & characterisation of limbal epithelial cells & oral mucosal cells. Indian J Med Res 131:422–428

    PubMed  Google Scholar 

  21. Sotozono C, Ang LP, Koizumi N, Higashihara H, Ueta M, Inatomi T, Yokoi N, Kaido M, Dogru M, Shimazaki J, Tsubota K, Yamada M, Kinoshita S (2007) New grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome. Ophthalmology 114:1294–1302

    Article  PubMed  Google Scholar 

  22. Qi X, Xie L, Cheng J, Zhai H, Zhou Q (2013) Characteristics of immune rejection after allogeneic cultivated limbal epithelial transplantation. Ophthalmology 120:931–936

    Article  PubMed  Google Scholar 

  23. Lange C, Feltgen N, Junker B, Schulze-Bonsel K, Bach M (2009) Resolving the clinical acuity categories "hand motion" and "counting fingers" using the Freiburg visual acuity test (FrACT). Graefes Arch Clin Exp Ophthalmol 247:137–142

    Article  CAS  PubMed  Google Scholar 

  24. Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, Kinoshita S (2006) Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol 141:267–275

    Article  PubMed  Google Scholar 

  25. Satake Y, Higa K, Tsubota K, Shimazaki J (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 

  26. Sotozono C, Inatomi T, Nakamura T, Koizumi N, Yokoi N, Ueta M, Matsuyama K, Miyakoda K, Kaneda H, Fukushima M, Kinoshita S (2013) Visual improvement after cultivated oral mucosal epithelial transplantation. Ophthalmology 120:193–200

    Article  PubMed  Google Scholar 

  27. Prabhasawat P, Ekpo P, Uiprasertkul M, Chotikavanich S, Tesavibul N (2012) Efficacy of cultivated corneal epithelial stem cells for ocular surface reconstruction. Clin Ophthalmol 6:1483–1492

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Shi W, Wang T, Gao H, Xie L (2009) Management of severe ocular burns with symblepharon. Graefes Arch Clin Exp Ophthalmol 247:101–106

    Article  PubMed  Google Scholar 

  29. Sen S, Sharma S, Gupta A, Gupta N, Singh H, Roychoudhury A, Mohanty S, Sen S, Nag TC, Tandon R (2011) Molecular characterization of explant cultured human oral mucosal epithelial cells. Invest Ophthalmol Vis Sci 52:9548–9554

    Article  CAS  PubMed  Google Scholar 

  30. Promprasit D, Bumroongkit K, Tocharus C, Mevatee U, Tananuvat N (2015) Cultivation and phenotypic characterization of rabbit epithelial cells expanded ex vivo from fresh and cryopreserved limbal and oral mucosal explants. Curr Eye Res 40:274–281

    Article  CAS  PubMed  Google Scholar 

  31. Eslani M, Baradaran-Rafii A, Ahmad S (2012) Cultivated limbal and oral mucosal epithelial transplantation. Semin Ophthalmol 27:80–93

    Article  PubMed  Google Scholar 

  32. Hata K, Kagami H, Ueda M, Torii S, Matsuyama M (1995) The characteristics of cultured mucosal cell sheet as a material for grafting; comparison with cultured epidermal cell sheet. Ann Plast Surg 34:530–538

    Article  CAS  PubMed  Google Scholar 

  33. Shimazaki J, Higa K, Kato N, Satake Y (2009) Barrier function of cultivated limbal and oral mucosal epithelial cell sheets. Invest Ophthalmol Vis Sci 50:5672–5680

    Article  PubMed  Google Scholar 

  34. Sotozono C, Inatomi T, Nakamura T, Koizumi N, Yokoi N, Ueta M, Matsuyama K, Kaneda H, Fukushima M, Kinoshita S (2014) Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity. Acta Ophthalmol 92:e447–e453

    Article  PubMed  PubMed Central  Google Scholar 

  35. Inatomi T, Nakamura T, Koizumi N, Sotozono C, Kinoshita S (2005) Current concepts and challenges in ocular surface reconstruction using cultivated mucosal epithelial transplantation. Cornea 24:S32–S38

    Article  PubMed  Google Scholar 

  36. Dhamodaran K, Subramani M, Matalia H, Jayadev C, Shetty R, Das D (2016) One for all: a standardized protocol for ex vivo culture of limbal, conjunctival and oral mucosal epithelial cells into corneal lineage. Cytotherapy 18:546–561

    Article  CAS  PubMed  Google Scholar 

  37. Satake Y, Dogru M, Yamane GY, Kinoshita S, Tsubota K, Shimazaki J (2008) Barrier function and cytologic features of the ocular surface epithelium after autologous cultivated oral mucosal epithelial transplantation. Arch Ophthalmol 126:23–28

    Article  PubMed  Google Scholar 

  38. Yokoi N, Kinoshita S (1995) Clinical evaluation of corneal epithelial barrier function with the slit-lamp fluorophotometer. Cornea 14:485–489

    Article  CAS  PubMed  Google Scholar 

  39. Kanayama S, Nishida K, Yamato M, Hayashi R, Sugiyama H, Soma T, Maeda N, Okano T, Tano Y (2007) Analysis of angiogenesis induced by cultured corneal and oral mucosal epithelial cell sheets in vitro. Exp Eye Res 85:772–781

    Article  CAS  PubMed  Google Scholar 

  40. Kanayama S, Nishida K, Yamato M, Hayashi R, Maeda N, Okano T, Tano Y (2009) Analysis of soluble vascular endothelial growth factor receptor-1 secreted from cultured corneal and oral mucosal epithelial cell sheets in vitro. Br J Ophthalmol 93:263–267

    Article  CAS  PubMed  Google Scholar 

  41. Sekiyama E, Nakamura T, Kawasaki S, Sogabe H, Kinoshita S (2006) Different expression of angiogenesis-related factors between human cultivated corneal and oral epithelial sheets. Exp Eye Res 83:741–746

    Article  CAS  PubMed  Google Scholar 

  42. Kinoshita S, Koizumi N, Sotozono C, Yamada J, Nakamura T, Inatomi T (2004) Concept and clinical application of cultivated epithelial transplantation for ocular surface disorders. Ocul Surf 2:21–33

    Article  PubMed  Google Scholar 

  43. Lim P, Fuchsluger TA, Jurkunas UV (2009) Limbal stem cell deficiency and corneal neovascularization. Semin Ophthalmol 24:139–148

    Article  PubMed  Google Scholar 

  44. Espana EM, Di Pascuale M, Grueterich M, Solomon A, Tseng SC (2004) Keratolimbal allograft in corneal reconstruction. Eye (Lond) 18:406–417

    Article  CAS  Google Scholar 

  45. DeSousa JL, Daya S, Malhotra R (2009) Adnexal surgery in patients undergoing ocular surface stem cell transplantation. Ophthalmolgy 116:235–242

    Article  Google Scholar 

  46. Han ES, Wee WR, Lee JH, Kim MK (2011) Long-term outcome and prognostic factor analysis for keratolimbal allografts. Graefes Arch Clin Exp Ophthalmol 249:1697–1704

    Article  PubMed  Google Scholar 

  47. Ang AY, Chan CC, Biber JM, Holland EJ (2013) Ocular surface stem cell transplantation rejection: incidence, characteristics, and outcomes. Cornea 32:229–236

    Article  PubMed  Google Scholar 

  48. Qi X, Xie L, Cheng J, Zhao J (2013) Clinical results and influential factors of modified large-diameter lamellar keratoplasty in the treatment of total limbal stem cell deficiency. Cornea 32:555–560

    Article  PubMed  Google Scholar 

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Funding

This study was supported by the Natural Science Foundation of Shandong Province (ZR2014HQ059) and the Young and Middle-Aged Scientists Research Awards Fund of Shandong Province (ZR2017BH004).

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Correspondence to Lixin Xie.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Wang, J., Qi, X., Dong, Y. et al. Comparison of the efficacy of different cell sources for transplantation in total limbal stem cell deficiency. Graefes Arch Clin Exp Ophthalmol 257, 1253–1263 (2019). https://doi.org/10.1007/s00417-019-04316-z

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  • DOI: https://doi.org/10.1007/s00417-019-04316-z

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