6. 再談外源性幹細胞存在的問題
外源性幹細胞需要移植,必須由醫生進行操作。外源性幹細胞進入體內後有一個轉換率問題。這方面有篇文章,現在忘了出處了。
除了分離問題、保存問題、轉換效率問題、排異問題、以及巨大的費用問題外,其實際功效並非如我們從新聞報道中所看到的那樣神奇:這些報道僅僅是個別成功的、短期的例子,而大量失敗的例子我們無從知曉。
幹細胞研究領域著名的科學家之一是喬治城大學醫學院Georgetown University Medical School Washington, D.C. 的教授David A. Prentice, 博士(也是美國家庭研究委員會成員)。他曾在2003年的總統生物研究道德委員會(the President』s Council on Bioethics)做報告, 並指出胚胎幹細胞和胚胎組織幹細胞的克隆(移植)治療是失敗的Therapeutic Cloning is a Failure。下面是他的一篇報告中所列出的一些失敗的例子:
Transplanted cells from cloned mouse embryo rejected 克隆的小鼠胚胎移植細胞被排斥 *WM Rideout et al., 「Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy,」 Cell 109, 17-27; 5 April 2002 (published online 8 March 2002) 「Our results raise the provocative possibility that even genetically matched cells derived by therapeutic cloning may still face barriers to effective transplantation for some disorders.」
• *RYL. Tsai, R Kittappa, and RDG McKay; 「Plasticity, niches, and the use of stem cells」; Developmental Cell 2, 707-712; June 2002
「Jaenisch addressed the possibility that ES clones derived by nuclear transfer technique could be used to correct genetic defects… However, the donor cells, although derived from the animals with the same genetic background, are rejected by the hosts.」
Clones may need to be gestated to 「harvest」already-differentiated tissues
*R Lanza et al.; 「Generation of histocompatible tissue using nuclear transplantation,」 Nature Biotechnology 20, 689-696; July 2002 (published online 3 June 2002)
*R Lanza et al., 「Regeneration of the infarcted heart with stem cells derived by nuclear transplantation,」 Circulation Research 94, 820-827, April 2004 (published online 10 Feb 2004)
Thomas Okarma, CEO, Geron Corporation says: 「The odds favoring success are
vanishingly small, and the costs are daunting.」 「It would take thousands of [human]
eggs on an assembly line to produce a custom therapy for a single person. The process is a nonstarter, commercially.」 , Geron Corporation 公司的首席執行官托馬斯歐卡瑪說:(克隆幹細胞)成功的幾率很小,但費用卻如無底洞,為了治療一位病人需要數千枚人類卵細胞。這個過程就商業運作來說可不是能從零開始的。
Denise Gellene, 「Clone Profit? Unlikely」, Los Angeles Times, 10 May 2002
Alan Trounson, Australian embryonic stem cell expert and a leader in the field worldwide, says that stem cell research has advanced so rapidly in the past few months that therapeutic cloning is now unnecessary. 澳大利亞胚胎幹細胞專家,此領域內國際領軍人物阿蘭-超森博士說,幹細胞研究發展的如此迅速,治療性克隆(幹細胞)現在沒有必要了。
「Therapeutic」 cloning places women at risk 治療性的克隆置女性於危險之中
Because both cloning and embryonic stem cell production are extremely inefficient, a tremendous number of eggs will be required. For example, to treat only the 17 million Diabetes patients in the U.S.Will require minimum of 850 million-1.7 billion human eggs(Optimistically 50-100 human eggs/patient, estimated cost US$100,000-200,000 由於克隆和胚胎幹細胞的效率及其低下,因此需要大量的人類卵子。例如,要治療美國1千7百萬糖尿病患者,只少需要8億5千萬到17億枚卵子(最樂觀的估計,每位病人需要50到100枚卵子,估計每人的費用為10萬到20萬美元.
Current or potential embryonic stem cell problems (胚胎幹細胞存在的問題):
• Difficult to establish and maintain 生成和維護困難
• Difficulty in obtaining pure cultures in the dish 獲得純的幹細胞培養困難
• Potential for tumor formation and tissue destruction 有潛在的腫瘤形成和細胞破壞
*Wakitani S et al.; 「Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint」; Rheumatology 42, 162-165; January 2003
• Questions regarding functional differentiation 功能性分化存在問題,見
*Hansson M et al., 「Artifactual insulin release from differentiated embryonic stem cells」, Diabetes 53, 2603-2609, October 2004
*Sipione S et al., 「Insulin expressing cells from differentiated embryonic stem cells are not beta cells」, Diabetologia 47, 499-508, 2004 (published online 14 Feb 2004)
*Rajagopal J et al.; 「Insulin staining of ES cell progeny from insulin uptake」; Science 299, 363; 17 Jan 2003
*Zhang YM et al.; 「Stem cell-derived cardiomyocytes demonstrate arrhythmic potential」; Circulation 106, 1294-1299; 3 September 2002
• Problem of immune rejection 免疫系統排斥的問題
• Genomic instability 基因不穩定性 (易癌變),見
*Cowan CA et al., 「Derivation of embryonic stem-cell lines from human blastocysts」, New England Journal ofMedicine 350, 13; published online 3 March 2004
*Draper JS et al., 「Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells」, Nature Biotechnology 22, 53-54; January 2004
*Humpherys S et al.; 「Epigenetic instability in ES cells and cloned mice」; Science 293, 95-97; 6 July 2001
• Few and modest successes in animals, no clinical treatments 主要在動物實驗中獲得少量的成功,沒有大量的臨床治療經驗
• Ethically contentious 道德問題
順便給一個連接,看看電影大片是怎麼拍出來的
http://www.youtube.com/watch?v=clnozSXyF4k