美國斯坦福大學(xué)醫(yī)學(xué)院和加州大學(xué)舊金山分校的科學(xué)家們成功地分離出人類睪丸的干細(xì)胞,。這些細(xì)胞雖然酷似胚胎干細(xì)胞,,能分化成人體3種主要組織類型中的任何一種,,但研究人員提醒說,,不要將它們與人類胚胎干細(xì)胞混為一談,。睪丸干細(xì)胞具有不同與人類胚胎干細(xì)胞的基因表達和調(diào)控模式,其增殖和分化并不像人類胚胎干細(xì)胞那樣積極,。該項發(fā)現(xiàn)刊登在1月份的《干細(xì)胞》雜志上,。
去年11月發(fā)表在《自然》雜志上的研究成果指出,睪丸干細(xì)胞像胚胎干細(xì)胞一樣具有多能性,。新的研究卻發(fā)現(xiàn),,睪丸干細(xì)胞似乎徘徊在一個灰色地帶,即介于真正的多能性和許多成體干細(xì)胞表現(xiàn)出的更為有限的特定組織多能性之間,。研究人員將這些細(xì)胞稱為“多能生殖干細(xì)胞”,。生殖細(xì)胞是指可在人體分化成精子和卵子的那些細(xì)胞。
論文的共同作者之一,、斯坦福大學(xué)人類胚胎干細(xì)胞研究和教育中心主任芮妮?雷爵佩拉博士認(rèn)為,,發(fā)揮這些細(xì)胞的優(yōu)勢,如用它們分化獲得與男性生殖相關(guān)的細(xì)胞,,可能要比把它們歸類為胚胎干細(xì)胞的超級模仿者要明智得多,。加州大學(xué)舊金山分校泌尿外科教授、男性不育癥專家保羅?圖雷克則認(rèn)為,,這些細(xì)胞具有治療不孕不育癥或其他男性疾病的潛力,。
研究人員以生物切片方法從19名確診為不育癥的臨床患者身上獲取睪丸細(xì)胞,并用一種與人類胚胎干細(xì)胞相似的方式進行培養(yǎng),,結(jié)果19個樣本中的2個產(chǎn)生了帶有許多多能細(xì)胞特性的細(xì)胞系,。
進一步研究顯示,這兩個多能細(xì)胞系能表達與多能性相關(guān)的很多基因,,但非全部,。這些細(xì)胞也能被誘導(dǎo),進而明確地分化成非睪丸神經(jīng)細(xì)胞前體,,且能表達為對保持多能細(xì)胞年輕及非特定來說至關(guān)重要的端粒酶,。然而,當(dāng)研究人員檢查細(xì)胞的甲基化模式(影響基因表達的DNA修改)時,,他們發(fā)現(xiàn),,與人類胚胎干細(xì)胞相比,新產(chǎn)生的細(xì)胞系在某一區(qū)域并沒有徹底地被甲基化,;而在另一區(qū)域,,甲基化現(xiàn)象要比人類胚胎干細(xì)胞更為嚴(yán)重。
最后,,當(dāng)研究人員將這種人體干細(xì)胞注入具有免疫缺陷的小鼠體內(nèi)時,,他們展現(xiàn)出了形成畸胎瘤(一種可形成多種細(xì)胞類型的腫瘤)的有限能力。干細(xì)胞積極增殖和分化形成的畸胎瘤是真正多能的標(biāo)志,??傊?,研究表明,從男性睪丸分離出的干細(xì)胞只具有真正的多能細(xì)胞的一些而非全部特性,。
芮妮認(rèn)為,這些細(xì)胞與人類胚胎干細(xì)胞在基因表達,、甲基化及形成畸胎瘤的能力上是不同的,,由生殖細(xì)胞完全重建人類胚胎干細(xì)胞還不太可能。(生物谷Bioon.com)
生物谷推薦原始出處:
Stem Cells,,Nina Kossack,,Renee A Reijo-Pera
Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells
Nina Kossack 1, Juanito Meneses 2, Shai Shefi 3, Ha Nam Nguyen 1, Shawn Chavez 1, Cory Nicholas 1, Joerg Gromoll 4, Paul J Turek 5, Renee A Reijo-Pera 1*
1 Institute for Stem Cell Biology and Regenerative Medicine; Department of Obstetrics and Gynecology; Stanford University School of Medicine, Palo Alto, CA 94304
2 Center for Reproductive Sciences and cDepartment of Urology; University of California San Francisco, San Francisco, CA 94043
3 Department of Urology; University of California San Francisco, San Francisco, CA 94043; Sheba Medical Center; Tel Hashomer 52621, Israel
4 Center of Reproductive Medicine and Andrology, University of Muenster, Domagkstrasse 11, D-48129 Muenster, Germany
5 Department of Urology; University of California San Francisco, San Francisco, CA 94043
Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells (MGSCs)) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogoniaderived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germ line. Data indicates that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a testis biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8-weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming.