近日,，以色列科學家宣布，日前他們成功將取自老年心臟衰竭患者的皮膚細胞轉(zhuǎn)化成了健康的心肌細胞,。這些細胞已被證明能夠發(fā)育成健康的心肌組織,，并通過了大鼠移植實驗的驗證，類似療法有望10年內(nèi)在臨床上獲得應(yīng)用,。相關(guān)論文發(fā)表在5月23日出版的《歐洲心臟期刊》（European Heart Journal ）上,。
負責該研究的以色列技術(shù)研究所研究員利奧爾·格普斯頓說，實驗表明完全可以將采自心臟衰竭老年患者的皮膚細胞培育成健康的心肌細胞,，而這種新培育出的心肌細胞幾乎和患者剛出生時的心肌細胞無異,，該療法未來有望成為拯救心臟病患者的重要手段。
心臟衰竭是由心肌受損所引起的一種疾病,，患病后心臟無法正常泵出足夠的血液來供應(yīng)身體各個器官活動及代謝的需求,，逐步失去心臟功能，該癥是導致65歲以上老年人入院的主要原因,，近年來發(fā)病更為普遍,。目前，對于嚴重心臟衰竭患者只能依靠機械設(shè)備或寄希望于心臟移植,。
此次研究中,，格普斯頓的團隊首先從兩名年齡分別是51歲和61歲的男性心臟衰竭患者身上獲取皮膚細胞，然后通過向皮膚細胞中添加3個基因和一種名為丙戊酸的小分子的方式將其轉(zhuǎn)化為誘導多能干細胞,，最后再培育成心肌細胞,。研究人員發(fā)現(xiàn)，這些由老年心臟衰竭患者的皮膚細胞培育成的心肌細胞和那些由健康的年輕志愿者提供的皮膚細胞培育成的心肌細胞一樣有效,。而后研究人員在實驗室中將心肌細胞與現(xiàn)有的心臟組織放在一起進行培養(yǎng),，結(jié)果發(fā)現(xiàn)24到48小時內(nèi)，兩種類型的組織就能夠一起跳動,。之后,，新組織被移植到健康大鼠的心臟，很快便與大鼠細胞建立連接,。
格普斯頓說,，在將這些組織移植到人體之前還需經(jīng)過許多測試和完善，因此該療法數(shù)年后才能在臨床上獲得應(yīng)用。但實驗證明了用患者自體細胞治療心臟病的夢想完全能夠?qū)崿F(xiàn),。
倫敦大學心血管病學教授約翰·馬丁說,，這是一項有趣的工作，有望成為一種有效的療法,，但在實際應(yīng)用前還有很多事情要做,。英國愛丁堡大學心臟病專家尼古拉斯·米爾斯說，雖然該療法在用于臨床前還需要進一步完善和細化,，但結(jié)果還是令人鼓舞，它代表著我們距有效修復心臟這一夢想又近了一步,。（生物谷Bioon.com）
doi:10.1093/eurheartj/ehs096
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Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients
Limor Zwi-Dantsis1,2, Irit Huber1, Manhal Habib1, Aaron Winterstern1, Amira Gepstein1, Gil Arbel1 and Lior Gepstein1,3,*
Aims Myocardial cell replacement therapies are hampered by a paucity of sources for human cardiomyocytes and by the expected immune rejection of allogeneic cell grafts. The ability to derive patient-specific human-induced pluripotent stem cells (hiPSCs) may provide a solution to these challenges. We aimed to derive hiPSCs from heart failure (HF) patients, to induce their cardiomyocyte differentiation, to characterize the generated hiPSC-derived cardiomyocytes (hiPSC-CMs), and to evaluate their ability to integrate with pre-existing cardiac tissue. Methods and results Dermal fibroblasts from two HF patients were reprogrammed by retroviral delivery of Oct4, Sox2, and Klf4 or by using an excisable polycistronic lentiviral vector. The resulting HF-hiPSCs displayed adequate reprogramming properties and could be induced to differentiate into cardiomyocytes with the same efficiency as control hiPSCs (derived from human foreskin fibroblasts). Gene expression and immunostaining studies confirmed the cardiomyocyte phenotype of the differentiating HF-hiPSC-CMs. Multi-electrode array recordings revealed the development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation. Next, functional integration and synchronized electrical activities were demonstrated between hiPSC-CMs and neonatal rat cardiomyocytes in co-culture studies. Finally, in vivo transplantation studies in the rat heart revealed the ability of the HF-hiPSC-CMs to engraft, survive, and structurally integrate with host cardiomyocytes. Conclusions Human-induced pluripotent stem cells can be established from patients with advanced heart failure and coaxed to differentiate into cardiomyocytes, which can integrate with host cardiac tissue. This novel source for patient-specific heart cells may bring a unique value to the emerging field of cardiac regenerative medicine.
