Cultivated Autologous Oral Mucosal Epithelial Transplantation

Summary

Earlier protocol for cultivated oral mucosal epithelial transplantation (COMET) requires trypsin/EDTA to isolate epithelial cells from tissue, and uses murine 3T3 cells as feeder cells, which results in biosafety concern. This study uses collagenase instead of trypsin/EDTA to isolate epithelial cells, and does not use 3T3 cells co-culture, so as to make an animal ingredient-free cell culture product. The purpose of the study is to evaluate the feasibility of the new protocol of COMET in clinical use.

Timeline

Start

2016-03-01

Primary completion

2024-12-31

Completion

2024-12-31

Publications

• Results Chen HC, Chen HL, Lai JY, Chen CC, Tsai YJ, Kuo MT, Chu PH, Sun CC, Chen JK, Ma DH. Persistence of transplanted oral mucosal epithelial cells in human cornea. Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4660-8. doi: 10.1167/iovs.09-3377. Epub 2009 May 20.
• Results Chen HC, Yeh LK, Tsai YJ, Lai CH, Chen CC, Lai JY, Sun CC, Chang G, Hwang TL, Chen JK, Ma DH. Expression of angiogenesis-related factors in human corneas after cultivated oral mucosal epithelial transplantation. Invest Ophthalmol Vis Sci. 2012 Aug 17;53(9):5615-23. doi: 10.1167/iovs.11-9293.
• Results Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, Kinoshita S. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006 Feb;141(2):267-275. doi: 10.1016/j.ajo.2005.09.003.
• Results Inatomi T, Nakamura T, Kojyo M, Koizumi N, Sotozono C, Kinoshita S. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol. 2006 Nov;142(5):757-64. doi: 10.1016/j.ajo.2006.06.004. Epub 2006 Sep 20.
• Results Li W, Sabater AL, Chen YT, Hayashida Y, Chen SY, He H, Tseng SC. A novel method of isolation, preservation, and expansion of human corneal endothelial cells. Invest Ophthalmol Vis Sci. 2007 Feb;48(2):614-20. doi: 10.1167/iovs.06-1126.
• Results Ma DH, Kuo MT, Tsai YJ, Chen HC, Chen XL, Wang SF, Li L, Hsiao CH, Lin KK. Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye (Lond). 2009 Jun;23(6):1442-50. doi: 10.1038/eye.2009.60. Epub 2009 Apr 17.
• Results Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004 Oct;88(10):1280-4. doi: 10.1136/bjo.2003.038497.
• Results Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011 Jul;95(7):942-6. doi: 10.1136/bjo.2010.188714. Epub 2010 Nov 19.
• Results Petsoglou C, Balaggan KS, Dart JK, Bunce C, Xing W, Ali RR, Tuft SJ. Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomised placebo-controlled double-masked trial. Br J Ophthalmol. 2013 Jan;97(1):28-32. doi: 10.1136/bjophthalmol-2012-302137. Epub 2012 Oct 20.
• Results Satake Y, Higa K, Tsubota K, Shimazaki J. Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011 Aug;118(8):1524-30. doi: 10.1016/j.ophtha.2011.01.039. Epub 2011 May 14.
• Results Takeda K, Nakamura T, Inatomi T, Sotozono C, Watanabe A, Kinoshita S. Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease. Am J Ophthalmol. 2011 Aug;152(2):195-201.e1. doi: 10.1016/j.ajo.2011.01.046. Epub 2011 Jun 8.
• Results Hsueh YJ, Huang SF, Lai JY, Ma SC, Chen HC, Wu SE, Wang TK, Sun CC, Ma KS, Chen JK, Lai CH, Ma DH. Preservation of epithelial progenitor cells from collagenase-digested oral mucosa during ex vivo cultivation. Sci Rep. 2016 Nov 8;6:36266. doi: 10.1038/srep36266.
• Ma DH, Hsueh YJ, Ma KS, Tsai YJ, Huang SF, Chen HC, Sun CC, Kuo MT, Chao AS, Lai JY. Long-term survival of cultivated oral mucosal epithelial cells in human cornea: generating cell sheets using an animal product-free culture protocol. Stem Cell Res Ther. 2021 Oct 7;12(1):524. doi: 10.1186/s13287-021-02564-7.

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