臨床眼科61巻7号

2007年07月発行

連載 今月の話題

眼表面の再生医療

著者： 久保田享¹ 西田幸二¹

所属機関： ¹東北大学医学部眼科学教室

ページ範囲：P.1145 - P.1151

　これまで瘢痕性の眼表面疾患に対する再建は困難で，全層角膜移植では非常に予後が不良であった。角膜上皮の幹細胞に関する基礎的研究の進歩や羊膜の眼科手術への利用によって術式の改良がなされていったものの，免疫学的な問題は克服できなかった。そこで，拒絶反応のない自己細胞を用いた再生医療が注目されるようになったが，その開発には組織工学的な手法が非常に重要であった。Stevens-Johnson症候群，眼類天疱瘡，熱・化学腐食などによる角膜上皮幹細胞疲弊症に対する角膜上皮の再生医療として，患者自身の角膜上皮幹細胞や口腔粘膜の幹細胞を細胞ソースとした培養角膜上皮シート移植が開発され，すでに臨床応用が開始されている。しかしオキュラーサーフェスの他の要素である涙液や眼瞼の管理についての問題は残っており，移植の長期予後をフォローするとともにさらなる研究が必要である。

参考文献

1）Thoft R：Conjunctival transplantation. Arch Ophthalmol　95：1425-1427, 1977

2）Thoft RA：Keratoepithelioplasty. Am J Ophthalmol　97：1-6, 1984

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

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

5）Kenyon KR, Tseng SC：Limbal autograft transplantation for ocular surface disorders. Ophthalmology　96：709-722, 1989

6）Thoft RA, Friend J：The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci　24：1442-1443, 1983

7）Nishida K：Tissue engineering of the cornea. Cornea　22：S28-S34, 2003

8）Nishida K, Kinoshita S, Ohashi Y et al：Ocular surface abnormalities in aniridia. Am J Ophthalmol　120：368-375, 1995

9）Kim JC, Tseng SC：Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea　14：473-484, 1995

10）Tseng SC, Tsubota K：Important concepts for treating ocular surface and tear disorders. Am J Ophthalmol　124：825-885, 1997

11）Tsubota K, Satake Y, Ohyama M et al：Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol　122：38-52, 1996

12）Kim JS, Kim JC, Na BK et al：Amniotic membrane patching promotes healing and inhibits proteinase activity on wound healing following acute corneal alkali burn. Exp Eye Res　70：329-337, 2000

13）Tseng SC, Li DQ, Ma X：Suppression of transforming growth factor-beta isoforms, TGF-beta receptor typeⅡ, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol　179：325-335, 1999

14）Tseng SC, Prabhasawat P, Barton K et al：Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol　116：431-441, 1998

15）Solomon A, Pires RT, Tseng SC：Amniotic membrane transplantation after extensive removal of primary and recurrent pterygia. Ophthalmology　108：449-460, 2001

16）Prabhasawat P, Tesavibul N, Komolsuradej W：Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol　85：1455-1463, 2001

17）Hanada K, Shimazaki J, Shimmura S et al：Multilayered amniotic membrane transplantation for severe ulceration of the cornea and sclera. Am J Ophthalmol　131：324-331, 2001

18）Shimazaki J, Kaido M, Shinozaki N et al：Evidence of long-term survival of donor-derived cells after limbal allograft transplantation. Invest Ophthalmol Vis Sci　40：664-668, 1999

19）Nelson JD, Wright JC：Conjunctival goblet cell densities in ocular surface disease. Arch Ophthalmol　102：1049-1451, 1984

20）Tseng SC, Hirst LW, Maumenee AE et al：Possible mechanisms for the loss of goblet cells in mucin-deficient disorders. Ophthalmology　91：545-552, 1984

21）Nishida K, Yamanishi K, Yamada K et al：Epithelial hyperproliferation and transglutaminase 1 gene expression in Stevens-Johnson syndrome conjunctiva. Am J Pathol　154：331-336, 1999

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

23）Tsai RJ, Li LM, Chen JK：Reconstruction of damaged corneas by transplantation of autologous limbal cells. N Engl J Med　13：86-93, 2000

24）Schwab IR, Reyes M, Isseroff RR：Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease. Am J Ophthalmol　130：543-544, 2000

25）Koizumi N, Inatomi T, Suzuki T et al：Cultivated corneal epithelial stem cell transplantation in ocular surface disorders. Ophthalmology　108：1569-1574, 2001

26）Rama P, Bonini S, Lambiase A et al：Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency. Transplantation　72：1478-1485, 2001

27）Nishida K, Yamato M, Hayashida Y et al：Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface. Transplantation　77：379-385, 2004

28）Yamato M, Utsumi M, Kushida AI et al：Thermo-responsive culture dishes allow the intact harvest of multilayered keratinocyte sheets without disperse by reducing temperature. Tissue Eng　7：473-480, 2001

29）Hayashida Y, Nishida K, Yamato M et al：Ocular surface reconstruction using autologous rabbit oral mucosal epithelial sheets fabricated ex vivo on a temperature-responsive culture surface. Invest Ophthalmol Vis Sci　46：1632-1639, 2005

30）Nishida K, Yamato M, Hayashida Y et al：Corneal reconstruction using tissue-engineered cell sheets comprising autologous oral mucosal Epithelium. N Engl J Med　351：1187-1196, 2004