幹細胞論壇

美國俄亥俄州的兒童醫院(Cincinnati Children hospital)日前利用誘導式多功能幹細胞(iPSC),取代胚胎細胞,第一次成功的分化成小腸細胞.這項研究已在12日發表在自然(nature)期刊中.
科學家利用iPSC誘導成小腸細胞
iPSC如同胚胎細胞,就有高度分化能力,可分化身體三個胚層的組織.科學家利用化學和蛋白質的生長因子,促使iPSC只分化出內胚層組織.內胚層組織包含體內的器官組織,像是食道、胃、小腸、胰臟、肺臟和肝臟.

美國喬治亞大學的研究團隊日前發現,罹患第一型糖尿病的男性病患可以利用睪丸的精原幹細胞(Spermatogonial Stem Cell;SSC),分化成胰島的β細胞,恢復胰島素的分泌,以降低血糖濃度.

第一型糖尿病為先天性基因的異常導致自體抗體產生,對抗自身的胰島細胞,使胰島素無法正常產生,導致血糖居高不下.第一型糖尿病於任何年齡都可發病,但好發於40歲病人.世界上有5-15%人罹患第一型糖尿病仰賴每天的胰島素施打,並無法作根本的治療.

印度科學家日前在新德里的基因工程與生物學(Genetic Engineering abd Biology)會議上,發表感染結核桿菌的病人能長期與細菌共處原因,是因為啟動幹細胞而達到自體平衡的狀態,這項發現也刊登在<美國科學院學報>(PNAS).
  
世界衛生組織(WHO)公佈,目前全球有1/3人口感染結核桿菌,但只有10%病人會引起肺結核,其餘90%病人處於長期潛伏的狀態.
當結核桿菌入侵時,人體的免疫系統會活化T淋巴球,破壞結核桿菌及其他外來物的入侵,產生發炎作用形成結核組織(granulomas).事實上,身體的間葉幹細胞(MSC)能受到結核菌的感染,而跑至受傷位置,調控T淋巴球的活性.

（中央社華盛頓8日法新電）美國科學家首創以幹細胞技術從2隻雄性老鼠身上孕育出幼鼠，科學家表示這項新突破可幫助保育瀕臨絕種的動植物，甚至有一天能幫助人類同性情侶擁有自己血緣基因的孩子。
據今天刊載於生殖科學期刊（journal Biology of Reproduction）的研究表示，德州再生科學家成功操控雄性（XY染色體）老鼠胚胎細胞，發展出「誘發性多功能性幹細胞」（induced pluripotent stem cells,iPS）細胞株。
這些「誘發性多功能性幹細胞」就是所謂已接受過基因重編，以便成為類胚胎幹細胞狀態的成人細胞。
部分從新細胞株成長出來的細胞會直接失去Y染色體，成為XO細胞。
這些XO細胞注入到雌性老鼠胚胎並移植到代理孕鼠體內後，就會生下帶有原先雄性老鼠X染色體的幼鼠。
這些幼鼠長大與正常的雄性鼠交配後，生下的幼鼠無論雄性或雌性，都帶有有原先2位鼠爸爸的基因。
這份研究是由美國德州大學的癌症治療中心（MD Anderson Cancer Center）研究員所執行。

英國劍橋和愛丁堡大學的科學家利用大鼠的動物實驗發現,大腦幹細胞可以再生髓鞘組織,修補受損的髓鞘,進而治療多發性硬化症.這項發現已刊登在自然期刊的神經科學領域[Nature Neuroscience].
髓鞘是包覆在神經纖維外圍,負責保護神經的組織,同時可以促進訊息的傳遞至大腦.多發性硬化症是因自體抗體的產生,破壞自身的髓鞘組織,使髓鞘漸漸消失,剩下疤痕稱之為硬化.
目前治療多發性硬化症的藥物其目標蛋白為--RXR-gamma,科學家發現RXR-gamma蛋白可以促進大腦幹細胞再生,重新分化髓鞘組織進行修補.動物實驗已被證實,科學家希望下一部能進行人體試驗,證實此項研究的安全性和效應.
Myelin damage potentially reversed using stem cells - hope for multiple sclerosis patients
Stem cells in the brain were found to regenerate myelin sheath which protect nerve fibers. Myelin also helps conduct electrical signals, impulses; it facilitates the good flow of electricity along the nervous system from the brain. Patients with multiple sclerosis (MS) have multiple areas where the myelin has disappeared, leaving a scar (sclerosis).

猶他大學的燒燙防護中心日前提出成功的醫療成果報告,利用幹細胞液體以噴灑方式直接針對燒燙傷部位進行治療.

研究證實,利用去除紅血球的血小板濃厚液,加上前趨細胞,鈣離子,凝血酵素噴灑至小範圍的燒燙傷組織,能有效的凝血並促進傷口的修護,比起傳統的植皮手術,幹細胞的修補較不易產生併發症.
此項醫療方式和去年12月澳洲研究中心的ReCell治療方法類似,Recell已盛行於澳洲,歐洲和中國,用於因意外引起的燒燙傷的快速治療.Recell的噴霧液中含分解酵素,可以分解受傷組織的基底細胞和角質細胞,促進凝血機制.

科學家日前發現不正常的血球可以透過回饋機制(feedback),影響自身的造血幹細胞,藉由改變基因的表現,使幹細胞不斷分裂與分化,修補缺損的血球.

科學家已在動物實驗中發現,轉錄因子Myb會抑制血小板產生,當失去此基因時,血小板會大量生產,此時不成熟的血小板會藉由訊息傳遞影響自身的造血幹細胞,以維持血小板的含量.
身體的幹細胞並非處於休息的狀態,會受到周邊血液血球生長情形而有所影響,進而調控自身的分裂與分化能力.

椎間盤的受損常引起下背疼痛, 早期認為軟骨無法再生因此沒有有效的治療方式,瑞典的科學家日前發現利用幹細胞可以再生軟骨組織,增厚椎間盤的距離,可使背部不再受到疼痛.

          
Stem cell advances can aid patients having back pain

1998科學家利用體外授精技術獲得胚胎幹細胞,2007日本Yamanaka教授利用皮膚細胞成功誘導回胚胎幹細胞,2010科學家再創新,繞過幹細胞的過程,直接利用體細胞轉型為另一個組織的前驅細胞.

將體細胞加入四個基因轉型成類似胚胎幹細胞,稱為誘導式多功能幹細胞(iPSC),開啟兩階段式細胞分化與器官修補工程.但發展至今,科學家發現iPSC的誘導過程需較長的時間,又易演變成癌細胞.後續分化成的體細胞也較不精確與成熟,整個生物工程相對比較困難又無效率.因此科學家發明[直接轉型技術](Direct Conversion),將一個體細胞轉型為需要修補組織的體細胞,繞過幹細胞的中間步驟.
從2008年開始,科學家利用小鼠模式成功將一種胰臟細胞轉型為另一種胰臟細胞.後續也有將皮膚細胞直接轉型為神經,心肌和血液細胞等研究.
每個人身體的細胞都帶有相同的基因,但是在分化過程中細胞會啟動不同的基因來表現,所以產生不同組織的體細胞.[直接轉型技術](Direct Conversion)就是植入啟動特定基因表現的訊息蛋白,使原本的細胞因表現特定基因而轉型成另一種體細胞.
這項發明技術仍面臨許多問題,像是轉型的細胞是否是正常?細胞是否可維持?技術是否穩定可靠?相信再過幾年,科學家會一一克服這些問題的所在.
 
Scientists trick cells into switching identities
Scientists are reporting early success at transforming one kind of specialized cell into another, a feat of biological alchemy that doctors may someday perform inside a patient's body to restore health.
So if a heart attack damages muscle tissue in the heart, for example, doctors may someday be able to get other cells in that organ to become muscle to help the heart pump.
That's a futuristic idea, but researchers are enthusiastic about the potential for the new direct-conversion approach.
"I think everyone believes this is really the future of so-called stem-cell biology," says John Gearhart of the University of Pennsylvania, one of many researchers pursuing this approach.
The concept is two steps beyond the familiar story of embryonic stem cells, versatile entities that can be coaxed to become cells of all types, like brain and blood. Scientists are learning to guide those transformations, which someday may provide transplant tissue for treating diseases like Parkinson's or diabetes.
It's still experimental. But at its root, it's really just harnessing and speeding up what happens in nature: a versatile but immature cell matures into a more specialized one.
The first step beyond that came in 2007, when researchers reversed the process. They got skin cells to revert to a state resembling embryonic stem cells. That opened the door to a two-part strategy: turn skin cells from a person into stem cells in the lab, and then run the clock forward to get whatever specialized cell you want for transplant.
The new direct-conversion approach avoids embryonic stem cells and the whole notion of returning to an early state. Why not just go directly from one specialized cell to another? It's like flying direct rather than scheduling a stopover.
Even short of researchers' dreams of fixing internal organs from within, Gearhart says direct conversion may offer some other advantages over more established ways of producing specialized cells. Using embryonic stem cells is proving to be inefficient and more difficult than expected, scientists say. For example, the heart muscle cells developed from them aren't fully mature, Gearhart noted.
And there's no satisfactory way yet to make mature insulin-producing cells of the pancreas, which might be useful for treating diabetes, says George Daley of Children's Hospital Boston and the Harvard Stem Cell Institute.
So direct conversion might offer a more efficient and faster way of getting the kinds of cells scientists want.
A glimpse of what might be possible through direct conversion emerged in 2008. Researchers got one kind of pancreatic cell to turn into another kind within living mice.
But far more dramatic changes have been reported in the past year in lab dishes, with scientists converting mouse skin cells into nerve cells and heart muscle cells. And just this month came success with human cells, turning skin cells into early stage blood cells.
The secret to these transformations is the fact that all cells of a person's body carry the same DNA code. But not all the genes are active at any one time. In fact, a cell's identity depends on its lineup of active genes. So, to convert a cell, scientists alter that combination by inserting chemical signals to activate particular genes.
"This is something that's really caught fire because it's an easy strategy to use," Gearhart said. "Everyone's out there trying their different combinations (of chemical signals) to see if they can succeed."
But success is not so easy. "There's a lot of experiments failing," Daley said. "A lot of people are just taking a trial-and-error approach, and that's fundamentally inefficient. And yet, it may create a breakthrough."
Even when the experiments work, there are plenty of questions to answer. Can this technique reliably produce transformed cells? Are these new cells normal? Or do they retain some hidden vestiges of their original identity that might cause trouble later on?
"When we make a duck look like a cat, it may look like a cat and meow, but whether it still has feathers is an issue," Daley said.
And ultimately: Would it be safe to transplant these cells into patients?
"We're a long way from showing safety and efficacy for any of these things," Gearhart said. "This stuff is all so new that we have a lot of work to do."
In any case, he and Daley said, scientists will still work with embryonic stem cells and the man-made versions first produced in 2007, called iPS cells. Those technologies clearly have places in various kinds of research, and it's not yet clear whether they or direct conversion will eventually prove best for manufacturing replacement cells for people.

美國研究團隊已發現利用病人自己的骨髓間葉幹細胞(MSC)來再生膀胱的醫學模式。這項發佈在《幹細胞》期刊上的研究特別與有非正常發育膀胱的幼兒有關，而且它代表向新器官移植療法邁出了新一步。

這項研究由西北大學範伯格醫學學校和兒童紀念研究中心Arun Sharma博士和Earl Cheng博士引導，以前對細胞再生能力的研究主要是在動物模型上，這些不能很好的被臨床所使用。
“對病人身上骨髓幹細胞的合理使用，為探索器官移植療法，尤其是膀胱再生，打開了新的道路。”高級專家Sharma說，“我們研究中的一些發現證明了這些采自骨髓的幹細胞的可塑性，這使他們成為這類工作的理想之選。”
研究小組發現骨髓間葉幹細胞（MSCs）在表面和生理上和膀胱光滑肌肉細胞（bSMCs）相似，這意味著MSCs可以作為有遭破壞風險的bSMCs的細胞替換。
“為了研究，我們開發了一種以靈長類動物為基礎的模型，把狒狒的膀胱和骨髓MSCs聯繫在一起去嘗試局部的膀胱再生，”Sharma說，“我們發現被整個研究使用的間葉幹細胞保持著在移植部位的穩定性，手術後10個星期依然保持活力。”
移植的骨髓細胞也保持著發揮光滑肌細胞主要特性的能力，有一個類似正常膀胱一樣的不間斷的收縮週期。
當前有關支配膀胱再生的細胞和分子之間的作用的資訊是很罕見的，然而該小組的研究演示了MSCs在局部膀胱再生的可行性，而且他們所使用的靈長性動物的模型給這些過程提供了有價值的見解。它們也可能被用到人身上。
“這個新發現的膀胱增殖模式給膀胱再生過程展現一個獨特的見解，而且強有力地證明了MSCs可以被組織工程學目的使用。”Sharma總結道，“這項研究中的非人類靈長動物膀胱增殖模型的建立也將進一步提供重要的非臨床數據，這些可能最終會被臨床所利用。”
“在生物工程上，膀胱修復不是一個簡單的事情。臨床的SIS材料和病人提供的MSCs的組合給進一步測試提供了一個很好組合”，《幹細胞》副總編Mark Pittenger說，“Sharma博士和他的同事推進了Anthony Atala博士的工作。在過去的幾年裏這個領域的進展是十分顯而易見的，並且更多臨床研究還是需要的。”
Scientists Use Bone Marrow MSCs for Partial Bladder Regeneration in Primates

Researchers in the U.S. reported on the development of a new technique that uses bone marrow mesenchymal stem cells (MSCs) to partially regenerate bladder tissue in nonhuman primates. They hope their achievement will provide new insights into the bladder-regeneration process in vivo, and ultimately lead to new approaches to correcting developmental bladder abnormalities in pediatric patients. The studies, reported by Arun Sharma, Ph.D., and Earl Cheng, Ph.D., from the Feinberg School of Medicine at Northwestern University, are published in Stem Cells, in a paper titled, A Non-Human Primate Model for Urinary Bladder Regeneration Utilizing Autologous Sources of Bone Marrow Derived Mesenchymal Stem Cells.

Therapeutic approaches to address developmental urinary bladder abnormalities in pediatric patients have to date relied heavily on surgical intervention in the form of bladder-augmentation cystoplasty, Drs. Sharma, Cheng, and colleagues report. However, the technique is beset by drawbacks and can only be considered a stopgap measure. Moreover, they add, clinical attempts to create functional bladder tissue and overcome the problems associated with traditional bladder augmentation have also been met by numerous obstacles. One such technique has used myelomeningocele patient-derived urothelial and bladder smooth muscle cells (bSMCs) to reconstruct the urothelium and smooth muscle components of the bladder. Although highly innovative in approach, the authors admit, “these studies demonstrated lackluster physiological effects and did not address the possibility that the use of pathologic bladder cells may eventually result in the reformation of a diseased bladder state as well as the decline in urodynamic function of patients undergoing this treatment.”

Drs. Sharma and Cheng’s approach instead used bone marrow MSCs that in a clinical setting would be taken from the patient. They found that such cells have both phenotypic and physiological similarities with bSMCs, which they hypothesized could allow the cells to serve as an alternative source of cells for damaged bSMCs.

“For our research we developed a primate-based model, using a baboon bladder in conjunction with bone marrow MSCs to attempt partial bladder regeneration,” Sharma explains. “We found that the mesenchymal stem cells used throughout the study retained the ability to populate a surgically grafted area while remaining active 10 weeks after surgery.”

The researchers hope their approach could provide valuable new insight into the cellular and molecular interactions that govern bladder regeneration. “The newly described bladder-augmentation model represents a unique insight into the bladder-regeneration process and provides strong evidence that MSCs can be exploited for tissue-engineering purposes,” Sharma concludes. “The nonhuman primate bladder-augmentation model established in this study will also further provide key preclinical data that may eventually be translated in a clinical setting.”