A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates.
A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates.
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DOI：
10.1126/scitranslmed.aan1145
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发表时间：
2017-11-01
影响因子：
17.1
通讯作者：
Kiem HP
中科院分区：
文献类型：
--
作者：
Radtke S;Adair JE;Giese MA;Chan YY;Norgaard ZK;Enstrom M;Haworth KG;Schefter LE;Kiem HP
骨髓移植后的造血重建被认为是由定向和多能祖细胞驱动的，随后是长期移植的造血干细胞（HSC）。在这里，我们观察到一群早期移植细胞表现出HSC样行为，在非人灵长类动物的自体清髓性移植模型中，这些细胞在体内长期存在。为了鉴定这一群体，我们鉴定了定义的非人灵长类造血干细胞和祖细胞（HSPC）亚群的表型和功能，并将其与人HSPC进行了比较。我们证明了CD 34 + CD 45 RA-CD 90+细胞的表型高度富集HSC。最重要的是，该人群完全支持非人灵长类动物移植模型中的快速短期恢复和稳健的多系造血，并定量预测移植成功率以及中性粒细胞和血小板恢复的时间。该细胞群的应用在HSC移植和基因治疗/编辑的背景中具有潜力。在非人灵长类动物中发现了一群具有上级移植和再生能力的造血干细胞。干细胞基因治疗和干细胞富集移植物移植的金标准靶细胞群是CD 34+细胞。然而，该群体中的大多数细胞不会有助于植入。使用一个强大的非人灵长类动物移植模型，我们确定了一个干细胞富集的亚表型的CD 34+细胞，这是专门负责植入。这种表型的细胞剂量与中性粒细胞和血小板植入相关，并可靠地预测移植成功。重要的是，我们观察到这些细胞与人类细胞的表型和转录组相似性。这些数据表明，精制细胞群具有移植潜力，包括基因治疗/编辑方法。
Hematopoietic reconstitution after bone marrow transplantation is thought to be driven by committed and multipotent progenitor cells followed by long-term engrafting hematopoietic stem cells (HSCs). Here, we observed a population of early-engrafting cells displaying HSC-like behavior, which persisted long-term in vivo in an autologous myeloablative transplant model in nonhuman primates. To identify this population, we characterized the phenotype and function of defined nonhuman primate hematopoietic stem and progenitor cell (HSPC) subsets and compared these to human HSPCs. We demonstrate that the phenotype of CD34+CD45RA-CD90+ cells is highly enriched for HSCs. Most importantly, this population fully supported rapid short-term recovery and robust multilineage hematopoiesis in the nonhuman primate transplant model, and quantitatively predicted transplant success and time to neutrophil and platelet recovery. Application of this cell population has potential in the setting of HSC transplantation and gene therapy/editing. A population of hematopoietic stem cells with superior engraftment and repopulating abilities has been identified in nonhuman primates. The gold standard target cell population for stem cell gene therapy and transplantion of stem cell enriched grafts are CD34+ cells. However, most of the cells within this population will not contribute to engraftment. Using a robust nonhuman primate transplantation model, we identified a stem cell-enriched sub-phenotype of CD34+ cells which is exclusively responsible for engraftment. Cell doses of this phenotype correlated with neutrophil and platelet engraftment and reliably predicted transplant success. Importantly, we observed phenotypic and transcriptomic similarity of these cells to human cells. These data suggest a refined cell population with potential in transplantation including gene therapy/editing approaches.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
DOI：
10.1084/jem.172.1.363
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lansdorp PM;Sutherland HJ;Eaves CJ
通讯作者：
Eaves CJ
影响因子：
16.6
作者：
Adair, Jennifer E.;Waters, Timothy;Kiem, Hans-Peter
通讯作者：
Kiem, Hans-Peter
影响因子：
20.3
作者：
Drize, N;Chertkov, J;Zander, A
通讯作者：
Zander, A
影响因子：
2.7
作者：
KATZ, FE;TINDLE, R;GREAVES, MF
通讯作者：
GREAVES, MF