日本熊本大學(xué)一個研究小組報告稱，他們利用實驗鼠胚胎干細(xì)胞（ES細(xì)胞）培養(yǎng)出分泌胰島素的胰島細(xì)胞，將其移植到患糖尿病的實驗鼠體內(nèi)后，獲得了滿意的療效，這一技術(shù)未來可能造福糖尿病患者。
此前，研究人員已嘗試過利用胚胎干細(xì)胞培養(yǎng)分泌胰島素的胰島β細(xì)胞，但都未能取得理想的結(jié)果，只能培養(yǎng)得到胰島前體細(xì)胞（成為胰島β細(xì)胞之前的一種細(xì)胞形態(tài)）。
研究小組為了找到胰島前體細(xì)胞分化成胰島β細(xì)胞時的必要物質(zhì)，全面篩查了胰島前體細(xì)胞的約1100個分子，并發(fā)現(xiàn)了可以增加胰島素分泌的2種分子。 研究人員據(jù)此掌握了將胚胎干細(xì)胞（ES細(xì)胞）培養(yǎng)成胰島β細(xì)胞的“秘密”，培養(yǎng)出的胰島β細(xì)胞擁有和正常實驗鼠匹敵的胰島素分泌能力。
研究人員將培養(yǎng)出的胰島β細(xì)胞移植到患有糖尿病的實驗鼠體內(nèi)，6周后實驗鼠的血糖基本下降到了正常值。
為重度糖尿病患者移植胰島細(xì)胞是一種有效的療法，不過胰島細(xì)胞提供者不足。利用胚胎干細(xì)胞（ES細(xì)胞）或誘導(dǎo)多功能干細(xì)胞（IPS細(xì)胞）培養(yǎng)胰島細(xì)胞將有望擴大糖尿病移植療法的機會。研究負(fù)責(zé)人粂昭苑說，在驗證其安全性等之后，希望10年內(nèi)投入實用。
相關(guān)研究論文已經(jīng)刊登在15日一期的《自然—化學(xué)生物學(xué)》雜志上。
生物谷推薦的英文摘要
Nature Chemical Biology doi:10.1038/nchembio.1410
VMAT2 identified as a regulator of late-stage β-cell differentiation
Daisuke Sakano Nobuaki Shiraki Kazuhide Kikawa Taiji Yamazoe Masateru Kataoka Kahoko Umeda Kimi Araki Di Mao Shirou Matsumoto Naomi Nakagata Olov Andersson Didier Stainier Fumio Endo Kazuhiko Kume Motonari Uesugi Shoen Kume
Cell replacement therapy for diabetes mellitus requires cost-effective generation of high-quality， insulin-producing， pancreatic β cells from pluripotent stem cells. Development of this technique has been hampered by a lack of knowledge of the molecular mechanisms underlying β-cell differentiation. The present study identified reserpine and tetrabenazine (TBZ)， both vesicular monoamine transporter 2 (VMAT2) inhibitors， as promoters of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Neurog3 (referred to henceforth as Ngn3)-positive endocrine precursors. VMAT2-controlled monoamines， such as dopamine， histamine and serotonin， negatively regulated β-cell differentiation. Reserpine or TBZ acted additively with dibutyryl adenosine 3'，5'-cyclic AMP， a cell-permeable cAMP analog， to potentiate differentiation of embryonic stem (ES) cells into β cells that exhibited glucose-stimulated insulin secretion. When ES cell–derived β cells were transplanted into AKITA diabetic mice， the cells reversed hyperglycemia. Our protocol provides a basis for the understanding of β-cell differentiation and its application to a cost-effective production of functional β cells for cell therapy.
