A Large-Scale Bank of Organ Donor Bone Marrow and Matched Mesenchymal Stem Cells for Promoting Immunomodulation and Transplant Tolerance.
A Large-Scale Bank of Organ Donor Bone Marrow and Matched Mesenchymal Stem Cells for Promoting Immunomodulation and Transplant Tolerance.
复制标题
用于促进免疫调节和移植耐受的大规模器官供者骨髓库和匹配的间充质干细胞。
DOI：
10.3389/fimmu.2021.622604
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Woods EJ
中科院分区：
文献类型：
--
作者：
Johnstone BH;Messner F;Brandacher G;Woods EJ
诱导实体器官和血管复合移植物的免疫耐受是移植医学的圣杯。这将导致终身免疫抑制的需要，这与严重的不良后果有关，如感染，癌症和肾衰竭。目前最有希望的耐受诱导方法是通过移植供体造血干细胞建立混合嵌合状态;然而，除活体供体肾移植外，混合嵌合方法在其他实体器官或血管复合同种异体移植物（VCA）的临床前或临床试验中尚未大规模实现持久的免疫耐受。Ossium Health建立了一个冷冻保存的骨髓（BM）库，称为“造血祖细胞（HPC），骨髓”，从已故器官捐赠者的椎体中回收。这一新的造血细胞移植来源将成为治疗恶性血液病以及诱导移植耐受的宝贵资源。此外，我们已经发现并开发了大量与HPC的椎体骨碎片副产物骨髓恢复过程紧密相关的间充质干（基质）细胞（MSC）来源。因此，这些脊椎骨粘附MSC（vBA-MSC）与从每个供体获得的库存BM相匹配，而不是第三方MSC，这增强了安全性和潜在的功效。来自超过30个供体的vBA-MSC的分离和表征已经证明，所述细胞与传统的BM-MSC没有不同;然而，它们的丰度比从活体供体BM抽吸物获得的丰度高> 1，000倍。根据我们自己未发表的数据以及其他人发表的报告，MSC促进嵌合体，特别是在限制造血干细胞和祖细胞（HSPC）数量方面，并通过控制和/或预防移植物抗宿主病（graft-vs.宿主病（GvHD）。因此，vBA-MSC有可能促进混合嵌合体，促进互补的外周免疫调节功能，并增加BM输注的安全性。HPC、Marrow和vBA-MSC在当前VCA和实体器官移植（SOT）耐受性临床方案中具有潜在用途，这些方案适用于“延迟耐受”。计划在后续阶段进行HPC、Marrow的当前试验，以纳入vBA-MSC用于VCA和SOT的耐受性。
Induction of immune tolerance for solid organ and vascular composite allografts is the Holy Grail for transplantation medicine. This would obviate the need for life-long immunosuppression which is associated with serious adverse outcomes, such as infections, cancers, and renal failure. Currently the most promising means of tolerance induction is through establishing a mixed chimeric state by transplantation of donor hematopoietic stem cells; however, with the exception of living donor renal transplantation, the mixed chimerism approach has not achieved durable immune tolerance on a large scale in preclinical or clinical trials with other solid organs or vascular composite allotransplants (VCA). Ossium Health has established a bank of cryopreserved bone marrow (BM), termed “hematopoietic progenitor cell (HPC), Marrow,” recovered from deceased organ donor vertebral bodies. This new source for hematopoietic cell transplant will be a valuable resource for treating hematological malignancies as well as for inducing transplant tolerance. In addition, we have discovered and developed a large source of mesenchymal stem (stromal) cells (MSC) tightly associated with the vertebral body bone fragment byproduct of the HPC, Marrow recovery process. Thus, these vertebral bone adherent MSC (vBA-MSC) are matched to the banked BM obtained from each donor, as opposed to third-party MSC, which enhances safety and potentially efficacy. Isolation and characterization of vBA-MSC from over 30 donors has demonstrated that the cells are no different than traditional BM-MSC; however, their abundance is >1,000-fold higher than obtainable from living donor BM aspirates. Based on our own unpublished data as well as reports published by others, MSC facilitate chimerism, especially at limiting hematopoietic stem and progenitor cell (HSPC) numbers and increase safety by controlling and/or preventing graft-vs.-host-disease (GvHD). Thus, vBA-MSC have the potential to facilitate mixed chimerism, promote complementary peripheral immunomodulatory functions and increase safety of BM infusions. Both HPC, Marrow and vBA-MSC have potential use in current VCA and solid organ transplant (SOT) tolerance clinical protocols that are amenable to “delayed tolerance.” Current trials with HPC, Marrow are planned with subsequent phases to include vBA-MSC for tolerance of both VCA and SOT.
登录
查看更多内容
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
影响因子：
3.5
作者：
Dodson BP;Levine AD
通讯作者：
Levine AD
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
影响因子：
8.9
作者：
Dabbs, AD;Dew, MA;Iacono, A
通讯作者：
Iacono, A
影响因子：
6.2
作者：
Dharnidharka, Vikas R.;Caillard, Sophie;Abbott, Kevin C.
通讯作者：
Abbott, Kevin C.