用自体干细胞纠正镰状细胞病

sunsong7

Correcting Sickle Cell Disease With Stem Cells
, N. @$ J  w& F) r4 `1 ~2 PScienceDaily (Sep. 28, 2011) — Using a patient's own stem cells, researchers at Johns Hopkins have corrected the genetic alteration that causes sickle cell disease (SCD), a painful, disabling inherited blood disorder that affects mostly African-Americans. The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene.
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This digitally-colorized scanning electron micrograph (SEM) revealed some of the comparative ultrastructural morphology between normal red blood cells (RBCs), and a sickle cell RBC (left). (Credit: CDC / Janice Haney Carr)
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The research team cautions that the work, done only in the laboratory, is years away from clinical use in patients, but should provide tools for developing gene therapies for SCD and a variety of other blood disorders.
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In an article published online August 31 in Blood, the researchers say they are one step closer to developing a feasible cure or long-term treatment option for patients with SCD, which is caused by a single DNA letter change in the gene for adult hemoglobin, the principle protein in red blood cells needed to carry oxygen. People who inherited two copies -- one from each parent -- of the genetic alteration, the red blood cells are sickle-shaped, rather than round. The misshapen red blood cells clog blood vessels, leading to pain, fatigue, infections, organ damage and premature death.- k3 @. b: m  i3 }# @# j/ z
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Although there are drugs and painkillers that control SCD symptoms, the only known cure -- achieved rarely -- has been bone marrow transplant. But because the vast majority of SCD patients are African-American and few African-Americans have registered in the bone marrow registry, it has been difficult to find compatible donors, says Linzhao Cheng, Ph.D., a professor of medicine and associate director for basic research in the Division of Hematology and also a member of the Johns HopkinsInstitute for Cell Engineering. "We're now one step closer to developing a combination cell and gene therapy method that will allow us to use patients' own cells to treat them."
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Using one adult patient at The Johns Hopkins Hospital as their first case, the researchers first isolated the patient's bone marrow cells. After generating induced pluripotent stem (iPS) cells -- adult cells that have been reprogrammed to behave like embryonic stem cells -- from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques.7 v9 o& Q& q$ r! P+ _7 [  R! u4 S

4 i/ }$ Z8 J. `5 ?The researchers sequenced the DNA from 300 different samples of iPS cells to identify those that contained correct copies of the hemoglobin gene and found four. Three of these iPS cell lines didn't pass muster in subsequent tests.
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- e4 x' ^2 T3 p% g2 c0 l"The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells," Cheng said.
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In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels. "We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene," explains Cheng. "We next have to learn how to properly convert these cells into mature red blood cells."
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Only one drug treatment has been approved by the FDA for treatment of SCD, hydroxyurea, whose use was pioneered by George Dover, M.D., the chief of pediatrics at the Johns Hopkins Children's Center. Outside of bone marrow transplants, frequent blood transfusions and narcotics can control acute episodes.
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$ \( z1 W% i; Y# t* y  w* W9 [' iThe research was funded by grants from the Maryland Stem Cell Fund and the National Institutes of Health, and a fellowship from the Siebel Foundation.! @5 {" n, x4 X
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http://www.sciencedaily.com/releases/2011/09/110928180416.htm

cao0709

谢谢
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naturalkillerce

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9 \/ `8 C. ^9 O- E2 `0 C! OJ. Zou, P. Mali, X. Huang, S. N. Dowey, L. Cheng. , A3 R  s  D% k8 E/ \
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Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease.  C3 C% c4 R: H# I7 V$ D' M
Blood, 2011; DOI: 10.1182/blood-2011-02-3355547 G! X3 r* O" U3 v

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naturalkillerce

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8 p7 o% M: ~# T' K镰刀状疾病是由于从父母遗传的两套染色体中血红蛋白基因同时存在一种DNA单碱基突变而造成的，使得红细胞由正常的圆形变为镰刀状，这种疾病在非洲裔美国人身上发病率相对较高。( _2 ^5 y  o* P/ u0 c  u
华裔科学家Linzhao Cheng教授和其他同事一起结合细胞治疗和基因治疗，从病人身上分离出骨髓细胞，然后利用细胞重编程技术产生诱导性多功能干细胞(iPSCs)，接着采用基因工程技术用正常的血红蛋白基因替换有缺陷的血红蛋白基因，并进行筛选获得血红蛋白基因得到矫正的iPSCs。
" y' q  C  \6 }) I5 u" t再利用iPSCs能够大量增殖，同时也能够变成任何种类的细胞，研究人员加入生长因子让得到矫正的iPSCs分化为未成熟的血红蛋白，经测试表明正常的血红蛋白基因在这些细胞后得到表达，不过比正常水平的一半还低。Cheng认为，这些未成熟的红细胞仍然表现得像胚胎干细胞，因此不能表达成年人中足够多的血红蛋白，他们的下一步就是研究如何正确地将这些未成熟的红细胞转化为成熟的红细胞。
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该技术目前还在实验室阶段，还未正式进入临床试验，不过研究人员希望，该技术最终能为治疗镰刀状疾病带来一种福音。

michaelgibh

为什么这篇文献没有免费的可以下载呢！！！