基于动员的造血干细胞移植:无化疗基因治疗和移植的新视角。

IF 6.7 2区 医学 Q1 Medicine
Daniele Canarutto, Attya Omer Javed, Gabriele Pedrazzani, Samuele Ferrari, Luigi Naldini
{"title":"基于动员的造血干细胞移植:无化疗基因治疗和移植的新视角。","authors":"Daniele Canarutto,&nbsp;Attya Omer Javed,&nbsp;Gabriele Pedrazzani,&nbsp;Samuele Ferrari,&nbsp;Luigi Naldini","doi":"10.1093/bmb/ldad017","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient's ones. Ex vivo HSC gene therapy (HSC-GT) is a form of HSCT in which HSCs, usually from an autologous source, are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow (BM) niche, which is required for the engraftment of infused cells. Here, we review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.</p><p><strong>Sources of data: </strong>Literature was reviewed from PubMed-listed peer-reviewed articles. No new data are presented in this article.</p><p><strong>Areas of agreement: </strong>Chemotherapy exerts short and long-term toxicity to haematopoietic and non-haematopoietic organs. Whenever chemotherapy is solely used to allow engraftment of donor HSCs, rather than eliminating malignant cells, as in the case of HSC-GT for inborn genetic diseases, non-genotoxic approaches sparing off-target tissues are highly desirable.</p><p><strong>Areas of controversy: </strong>In principle, HSCs can be temporarily moved from the BM niches using mobilizing drugs or selectively cleared with targeted antibodies or immunotoxins to make space for the infused cells. However, translation of these principles into clinically relevant settings is only at the beginning, and whether therapeutically meaningful levels of chimerism can be safely established with these approaches remains to be determined.</p><p><strong>Growing points: </strong>In pre-clinical models, mobilization of HSCs from the niche can be tailored to accommodate the exchange and engraftment of infused cells. Infused cells can be further endowed with a transient engraftment advantage.</p><p><strong>Areas timely for developing research: </strong>Inter-individual efficiency and kinetics of HSC mobilization need to be carefully assessed. Investigations in large animal models of emerging non-genotoxic approaches will further strengthen the rationale and encourage application to the treatment of selected diseases.</p>","PeriodicalId":9280,"journal":{"name":"British medical bulletin","volume":"147 1","pages":"108-120"},"PeriodicalIF":6.7000,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/dc/ldad017.PMC10502445.pdf","citationCount":"0","resultStr":"{\"title\":\"Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.\",\"authors\":\"Daniele Canarutto,&nbsp;Attya Omer Javed,&nbsp;Gabriele Pedrazzani,&nbsp;Samuele Ferrari,&nbsp;Luigi Naldini\",\"doi\":\"10.1093/bmb/ldad017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient's ones. Ex vivo HSC gene therapy (HSC-GT) is a form of HSCT in which HSCs, usually from an autologous source, are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow (BM) niche, which is required for the engraftment of infused cells. Here, we review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.</p><p><strong>Sources of data: </strong>Literature was reviewed from PubMed-listed peer-reviewed articles. No new data are presented in this article.</p><p><strong>Areas of agreement: </strong>Chemotherapy exerts short and long-term toxicity to haematopoietic and non-haematopoietic organs. Whenever chemotherapy is solely used to allow engraftment of donor HSCs, rather than eliminating malignant cells, as in the case of HSC-GT for inborn genetic diseases, non-genotoxic approaches sparing off-target tissues are highly desirable.</p><p><strong>Areas of controversy: </strong>In principle, HSCs can be temporarily moved from the BM niches using mobilizing drugs or selectively cleared with targeted antibodies or immunotoxins to make space for the infused cells. However, translation of these principles into clinically relevant settings is only at the beginning, and whether therapeutically meaningful levels of chimerism can be safely established with these approaches remains to be determined.</p><p><strong>Growing points: </strong>In pre-clinical models, mobilization of HSCs from the niche can be tailored to accommodate the exchange and engraftment of infused cells. Infused cells can be further endowed with a transient engraftment advantage.</p><p><strong>Areas timely for developing research: </strong>Inter-individual efficiency and kinetics of HSC mobilization need to be carefully assessed. Investigations in large animal models of emerging non-genotoxic approaches will further strengthen the rationale and encourage application to the treatment of selected diseases.</p>\",\"PeriodicalId\":9280,\"journal\":{\"name\":\"British medical bulletin\",\"volume\":\"147 1\",\"pages\":\"108-120\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2023-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/dc/ldad017.PMC10502445.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British medical bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/bmb/ldad017\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British medical bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/bmb/ldad017","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

简介:在造血干细胞移植(HSCT)中,来自健康供体的造血干细胞(HSC)取代了患者的造血干电池。离体HSC基因治疗(HSC-GT)是HSCT的一种形式,其中通常来自自体来源的HSC在输注前进行基因修饰,以产生基因修饰细胞的后代。在HSCT和HSC-GT中,化疗是在输注到骨髓(BM)生态位的自由空间之前进行的,这是植入输注细胞所必需的。在此,我们回顾了替代常规方案并降低手术发病率的无化疗小生境排尿的替代方法。数据来源:文献来自PubMed列出的同行评审文章。本文中没有提供新的数据。一致的领域:化疗对造血和非造血器官产生短期和长期毒性。每当化疗仅用于移植供体HSC,而不是消除恶性细胞时,如先天性遗传疾病的HSC-GT,非常需要保留靶组织的非基因毒性方法。争议领域:原则上,HSC可以使用动员药物暂时从BM小生境中移出,或者用靶向抗体或免疫毒素选择性清除,为注入的细胞腾出空间。然而,将这些原理转化为临床相关环境才刚刚开始,使用这些方法是否可以安全地建立有治疗意义的嵌合水平仍有待确定。生长点:在临床前模型中,可以对HSC从壁龛中的动员进行定制,以适应输注细胞的交换和植入。注入的细胞可以被进一步赋予短暂的植入优势。及时开展研究的领域:需要仔细评估HSC动员的个体间效率和动力学。对新出现的非基因毒性方法的大型动物模型的研究将进一步加强理论基础,并鼓励应用于选定疾病的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.

Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.

Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.

Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.

Introduction: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient's ones. Ex vivo HSC gene therapy (HSC-GT) is a form of HSCT in which HSCs, usually from an autologous source, are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow (BM) niche, which is required for the engraftment of infused cells. Here, we review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.

Sources of data: Literature was reviewed from PubMed-listed peer-reviewed articles. No new data are presented in this article.

Areas of agreement: Chemotherapy exerts short and long-term toxicity to haematopoietic and non-haematopoietic organs. Whenever chemotherapy is solely used to allow engraftment of donor HSCs, rather than eliminating malignant cells, as in the case of HSC-GT for inborn genetic diseases, non-genotoxic approaches sparing off-target tissues are highly desirable.

Areas of controversy: In principle, HSCs can be temporarily moved from the BM niches using mobilizing drugs or selectively cleared with targeted antibodies or immunotoxins to make space for the infused cells. However, translation of these principles into clinically relevant settings is only at the beginning, and whether therapeutically meaningful levels of chimerism can be safely established with these approaches remains to be determined.

Growing points: In pre-clinical models, mobilization of HSCs from the niche can be tailored to accommodate the exchange and engraftment of infused cells. Infused cells can be further endowed with a transient engraftment advantage.

Areas timely for developing research: Inter-individual efficiency and kinetics of HSC mobilization need to be carefully assessed. Investigations in large animal models of emerging non-genotoxic approaches will further strengthen the rationale and encourage application to the treatment of selected diseases.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
British medical bulletin
British medical bulletin 医学-医学:内科
CiteScore
13.10
自引率
1.50%
发文量
24
审稿时长
>12 weeks
期刊介绍: British Medical Bulletin is a multidisciplinary publication, which comprises high quality reviews aimed at generalist physicians, junior doctors, and medical students in both developed and developing countries. Its key aims are to provide interpretations of growing points in medicine by trusted experts in the field, and to assist practitioners in incorporating not just evidence but new conceptual ways of thinking into their practice.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信