干细胞和人体组的自我修复 ---6 再谈外源性干细胞存在的问题

6. 再谈外源性干细胞存在的问题

外源性干细胞需要移植，必须由医生进行操作。外源性干细胞进入体内后有一个转换率问题。这方面有篇文章，现在忘了出处了。

除了分离问题、保存问题、转换效率问题、排异问题、以及巨大的费用问题外，其实际功效并非如我们从新闻报道中所看到的那样神奇：这些报道仅仅是个别成功的、短期的例子，而大量失败的例子我们无从知晓。

干细胞研究领域著名的科学家之一是乔治城大学医学院Georgetown University Medical School Washington, D.C. 的教授David A. Prentice, 博士（也是美国家庭研究委员会成员）。他曾在2003年的总统生物研究道德委员会（the President’s Council on Bioethics）做报告， 并指出胚胎干细胞和胚胎组织干细胞的克隆（移植）治疗是失败的Therapeutic Cloning is a Failure。下面是他的一篇报告中所列出的一些失败的例子：
Transplanted cells from cloned mouse embryo rejected 克隆的小鼠胚胎移植细胞被排斥 *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 公司的首席执行官托马斯欧卡玛说：（克隆干细胞）成功的几率很小，但费用却如无底洞，为了治疗一位病人需要数千枚人类卵细胞。这个过程就商业运作来说可不是能从零开始的。
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. 澳大利亚胚胎干细胞专家，此领域内国际领军人物阿兰-超森博士说，干细胞研究发展的如此迅速，治疗性克隆（干细胞）现在没有必要了。
“Therapeutic” cloning places women at risk 治疗性的克隆置女性于危险之中
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 由于克隆和胚胎干细胞的效率及其低下，因此需要大量的人类卵子。例如，要治疗美国1千7百万糖尿病患者，只少需要8亿5千万到17亿枚卵子（最乐观的估计，每位病人需要50到100枚卵子，估计每人的费用为10万到20万美元.

Current or potential embryonic stem cell problems （胚胎干细胞存在的问题）:
• Difficult to establish and maintain 生成和维护困难
• Difficulty in obtaining pure cultures in the dish  获得纯的干细胞培养困难
• Potential for tumor formation and tissue destruction 有潜在的肿瘤形成和细胞破坏
*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  功能性分化存在问题，见
*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  免疫系统排斥的问题
• Genomic instability 基因不稳定性 （易癌变），见
*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 主要在动物实验中获得少量的成功，没有大量的临床治疗经验
• Ethically contentious  道德问题

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