新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » Science报道 » Sci Transl Med:生物工程改造的干细胞可改善肾移植患者的生活质量

Sci Transl Med:生物工程改造的干细胞可改善肾移植患者的生活质量

来源:EurekAlert! 2012-03-08 10:30

近日,国际著名杂志Science Translational Medicine在线刊登了国外研究人员的最新研究成果“Chimerism and Tolerance Without GVHD or Engraftment Syndrome in HLA-Mismatched Combined Kidney and Hematopoietic Stem Cell Transplantation,”,在这项研究中,研究者表示,用生物工程改造过的干细胞可以明显改善肾移植患者的生活品质。

在一小群人中所做的一项新的研究报告说,用改良过的骨髓干细胞进行治疗可帮助肾移植患者摆脱免疫抑制性药物。

该发现可减少或消除对有毒的免疫抑制性药物的需要——最多可达每日15-25粒——为了防止移植物被排斥,大多数的器官移植病人需要在他们的余生中服用这么多的药物。因为免疫系统已经进化了来抗感染、不接受异体器官,免疫细胞因此无法分辨入侵者的好坏。免疫抑制性药物的使用是为了控制免疫反应,这对保持体内异体器官的存活是至关重要的,但它们也会带来像高血压、糖尿病及感染风险增加等有害的副作用。 把来自移植器官接受者与捐赠者的骨髓干细胞混合起来可帮助改善器官的耐受性,但它也会引发移植物抗宿主病(GVHD),即器官捐赠者的免疫细胞攻击器官接受者的健康组织。

Joseph Leventhal及其同事表明,在肾移植时给予患者来自其自身的经生物工程改造过的骨髓干细胞可防止GVHD。 该小组首先用会将干细胞从骨髓中引诱出来的药物来治疗8位器官移植患者。研究人员通过让干细胞富含移植物促进细胞并清除某些会引起GVHD的细胞而使它们变得对移植物更加友善。 2周之后,患者接受了他们的移植肾脏及改造过的骨髓干细胞。8位病人中有5位令人惊讶地维持了长时期的正常肾功能并在1年内停止服用免疫抑制性药物。正如一则相关的《观点栏目》所指出的,这种方法可能会使某些人从与终生免疫抑制有关的困难中解脱出来,并使那些没有匹配捐赠者的病人的器官移植成为一种可行的选项。(生物谷Bioon.com)

Chimerism and Tolerance Without GVHD or Engraftment Syndrome in HLA-Mismatched Combined Kidney and Hematopoietic Stem Cell Transplantation

Joseph Leventhal1, Michael Abecassis1, Joshua Miller1, Lorenzo Gallon1, Kadiyala Ravindra2, David J. Tollerud2,3, Bradley King2,3, Mary Jane Elliott2, Geoffrey Herzig4, Roger Herzig4 and Suzanne T. Ildstad2,3,*

The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)–mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.

本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库