自體口腔黏膜細胞可以重建角膜


  Sept. 15, 2004 - 根據一份發表於9月16日新英格蘭醫學期刊上的報導指出,自體口腔黏膜上皮可以用來重建角膜。
  
  日本大阪大學醫學院Kohji Nishida醫師表示,角膜傷害或疾病可能造成嚴重地使角膜混濁,因為角膜上皮幹細胞完全死亡而造成嚴重視覺喪失;自體角膜幹細胞來源的移植是同種異體移植以外的選擇,而且不需要免疫抑制,但是在許多情況下是不可能的,例如雙側疾病造成雙眼角膜幹細胞完全缺陷。
  
  新的移植方式使用對溫度有反應的培養表面,透過降低溫度,研究人員可以將所有培養細胞從表面分離,以完整可移植的細胞層,不需要任何載體或是來自移植物的骨架。
  
  在4位雙側幹細胞完全缺失的病患,取下3乘3的口腔黏膜組織樣本,而且被取下的細胞與使用3T3細胞鋪成的細胞層以mitomycin C處理,共同培養2個星期;結膜纖維血管組織利用外科從角膜表面切除,而且培養的自體細胞直接地移植到每位病患一隻眼睛裸露的表面,不需要縫合。
  
  在一個星期中,所有4位已治療眼睛的角膜表面重新長出上皮,角膜的透明度恢復,而且術後視力戲劇性地改善;在14個月的追蹤,所有角膜表面仍然是透明的,而且沒有發現併發症。
  
  研究人員指出,組織工程的上皮細胞層組裝成來自自體口腔黏膜上皮,對於雙側幹細胞完全缺失病患要重建角膜表面與恢復視力是有效的;不過,仍需要大量病患長期的追蹤與經驗,來評估這個方式是否能進一步提供對標準治療無效之嚴重角膜疾病者有潛力的治療,以及其利益與風險。
  
  日本教育、文化、運動、科學、與科技部以及來自日本的演化科學與技術核心研究還有科學與技術署贊助這項試驗。
  
  義大利Osepedale Civile di Venezia的Graziella Pellegrini博士在隨後的評論中表示,當沒有損傷的培養上皮細胞被移植到角膜表面時,它們會使角膜表面變得適合細胞生存的微環境;這可能造成接受者本身幹細胞的刺激與增殖;人類的角膜表面,因為其與不同形式細胞的位置界限清楚,提供了細胞治療有用的模型;此外,肢體的幹細胞移植可能為其他組織或器官的幹細胞療法鋪路。

Autologous Oral Mucosal Cells<

By Laurie Barclay, MD
Medscape Medical News

Sept. 15, 2004 — Autologous oral mucosal epithelium can be used for corneal reconstruction, according to a report in the Sept. 16 issue of the New England Journal of Medicine.

"Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells," write Kohji Nishida, MD, PhD, from Osaka University Medical School in Japan, and colleagues. "Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes."

This new transplantation method uses temperature-responsive culture surfaces. By lowering the temperature, the investigators were able to detach all the cultured cells from the surfaces as an intact transplantable cell sheet and to exclude any carrier or scaffold from the graft.

In four patients with bilateral total corneal stem-cell deficiencies, 3-by-3-mm specimens of oral mucosal tissue were harvested, and the harvested cells were cultured for two weeks with 3T3 feeder cells that had been treated with mitomycin C. Conjunctival fibrovascular tissue was surgically excised from the ocular surface, and sheets of cultured autologous cells were transplanted directly to denuded corneal surface of one eye of each patient, without using sutures.

Within one week, all four treated eyes had complete reepithelialization of the corneal surfaces, with restoration of corneal transparency and dramatic postoperative improvement in visual acuity. During a mean follow-up period of 14 months, all corneal surfaces remained transparent, and no complications were reported.

"Sheets of tissue-engineered epithelial cells fabricated ex vivo from autologous oral mucosal epithelium are effective for reconstructing the ocular surface and restoring vision in patients with bilateral total stem-cell deficiencies," the authors write. "Long-term follow-up and experience with a large series of patients are needed to assess further the benefits and risks of this method, which offers the potential to treat severe ocular diseases that are resistant to standard approaches."

The Ministry of Education, Culture, Sports, Science, and Technology in Japan and the Core Research for Evolution Science and Technology from the Japan Science and Technology Agency supported this study.

"When undamaged cultured epithelial cells are transplanted onto the ocular surface, they induce modifications of the microenvironment that make the ocular surface suitable for cell survival; this may result in the stimulation and proliferation of the recipient's own stem cells," Graziella Pellegrini, PhD, from the Ospedale Civile di Venezia in Italy, writes in an accompanying perspective. "The human ocular surface, with its well-defined locations for different types of cells, provides a useful model for cell therapy. Additional experience with limbal stem-cell transplantation may pave the way for stem-cell therapy for other tissues and organs."

N Engl J Med. 2004;351:1170-1172, 1187-1196

Reviewed by Gary D. Vogin, MD

    
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