Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis.
Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis.
复制标题
DOI：
10.3791/61875
复制
发表时间：
2021-05-26
期刊：
影响因子：
--
通讯作者：
Walsh K
中科院分区：
文献类型：
--
作者：
Park E;Evans MA;Doviak H;Horitani K;Ogawa H;Yura Y;Wang Y;Sano S;Walsh K
克隆性造血是一种常见的年龄相关性疾病，由造血干细胞和祖细胞（HSPC）中体细胞突变的积累引起。赋予细胞适应性的驱动基因中的突变可导致扩展的HSPC克隆的发展，其越来越多地产生携带体细胞突变的后代白细胞。由于克隆造血与心脏病、中风和死亡率有关，因此开发模拟这些过程的实验系统是理解这一新风险因素机制的关键。涉及小鼠清髓性预处理的骨髓移植程序，例如全身照射（TBI），通常用于研究免疫细胞在心血管疾病中的作用。然而，这些手术不可避免地会同时损伤骨髓龛和其他感兴趣的部位，如心脏和大脑。因此，我们的实验室已经开发了两种替代方法来最大限度地减少或避免TBI引起的可能的副作用：1）辐射屏蔽骨髓移植和2）非条件小鼠的过继BMT。在屏蔽的器官中，局部环境被保留，允许分析克隆造血，同时常驻免疫细胞的功能不受干扰。相比之下，非条件小鼠的过继性BMT具有额外的优点，即器官的局部环境和造血生态位都得到了保护。在这里，我们比较了三种不同的造血细胞重建方法，并讨论了他们的优势和局限性的研究克隆造血在心血管疾病。
Clonal hematopoiesis is a prevalent age-associated condition that results from the accumulation of somatic mutations in hematopoietic stem and progenitor cells (HSPCs). Mutations in driver genes, that confer cellular fitness, can lead to the development of expanding HSPC clones that increasingly give rise to progeny leukocytes harboring the somatic mutation. Because clonal hematopoiesis has been associated with heart disease, stroke, and mortality, the development of experimental systems that model these processes is key to understanding the mechanisms that underly this new risk factor. Bone marrow transplantation procedures involving myeloablative conditioning in mice, such as total-body irradiation (TBI), are commonly employed to study the role of immune cells in cardiovascular diseases. However, simultaneous damage to the bone marrow niche and other sites of interest, such as the heart and brain, is unavoidable with these procedures. Thus, our lab has developed two alternative methods to minimize or avoid possible side effects caused by TBI: 1) bone marrow transplantation with irradiation shielding and 2) adoptive BMT to non-conditioned mice. In shielded organs, the local environment is preserved allowing for the analysis of clonal hematopoiesis while the function of resident immune cells is unperturbed. In contrast, the adoptive BMT to non-conditioned mice has the additional advantage that both the local environments of the organs and the hematopoietic niche are preserved. Here, we compare three different hematopoietic cell reconstitution approaches and discuss their strengths and limitations for studies of clonal hematopoiesis in cardiovascular disease.
登录
查看更多内容
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
24
作者：
Lavine KJ;Pinto AR;Epelman S;Kopecky BJ;Clemente-Casares X;Godwin J;Rosenthal N;Kovacic JC
通讯作者：
Kovacic JC
影响因子：
3.7
作者：
Koch A;Gulani J;King G;Hieber K;Chappell M;Ossetrova N
通讯作者：
Ossetrova N
影响因子：
64.5
作者：
Welch JS;Ley TJ;Link DC;Miller CA;Larson DE;Koboldt DC;Wartman LD;Lamprecht TL;Liu F;Xia J;Kandoth C;Fulton RS;McLellan MD;Dooling DJ;Wallis JW;Chen K;Harris CC;Schmidt HK;Kalicki-Veizer JM;Lu C;Zhang Q;Lin L;O'Laughlin MD;McMichael JF;Delehaunty KD;Fulton LA;Magrini VJ;McGrath SD;Demeter RT;Vickery TL;Hundal J;Cook LL;Swift GW;Reed JP;Alldredge PA;Wylie TN;Walker JR;Watson MA;Heath SE;Shannon WD;Varghese N;Nagarajan R;Payton JE;Baty JD;Kulkarni S;Klco JM;Tomasson MH;Westervelt P;Walter MJ;Graubert TA;DiPersio JF;Ding L;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
4.3
作者：
Bacigalupo, Andrea;Ballen, Karen;Rizzo, Doug;Giralt, Sergio;Lazarus, Hillard;Ho, Vincent;Apperley, Jane;Slavin, Shimon;Pasquini, Marcelo;Sandmaier, Brenda M.;Barrett, John;Blaise, Didier;Lowski, Robert;Horowitz, Mary
通讯作者：
Horowitz, Mary