Numbers of long-term hematopoietic stem cells from bone marrow of fanca and fancc knockout mice can be greatly enhanced by their collection and processing in physioxia conditions.
Numbers of long-term hematopoietic stem cells from bone marrow of fanca and fancc knockout mice can be greatly enhanced by their collection and processing in physioxia conditions.
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从fanca和fancc基因敲除小鼠的骨髓中收集长期造血干细胞，并在生理氧条件下进行处理，可大大提高其数量。
DOI：
10.1016/j.bcmd.2020.102492
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Clapp DW
中科院分区：
文献类型：
--
作者：
Broxmeyer HE;Capitano ML;Cooper S;Potchanant ES;Clapp DW
范可尼贫血（FA）与骨髓衰竭有关。来自FA患者和fanca−/−和fancc−/−小鼠的骨髓（BM）缺乏造血干细胞（HSC）和祖细胞（HPC）。减少的HSC/HPC损害它们在人类和小鼠造血细胞移植（HCT）和基因治疗中的使用，以纠正导致FA的遗传缺陷。我们报道了在低氧（3%）条件下（生理氧）采集/处理后，从小鼠骨髓和动员的外周血以及正常供体的人脐带血中采集的HSC增加。我们评估了在3%O2下收集/处理时来自fanca−/−和fancc−/− BM的长期（LT）-HSC的比较含量，以消除在环境空气中收集/处理诱导的额外生理休克应激（EPHOSS）的影响。在物理氧环境中收集/处理fanca−/−和fancc−/−小鼠的BM表明，与环境空气相比，LT-HSC增加≥3倍。这与表型多能祖细胞和功能性粒细胞巨噬细胞、红细胞和多能祖细胞减少有关，结果与正常供体小鼠BM相似。增加HSC的收集可能具有基因治疗和HCT的临床适用性。
Fanconi anemia (FA) is associated with bone marrow failure. Bone marrow (BM) from patients with FA and fanca−/− and fancc−/− mice are deficient in hematopoietic stem (HSCs) and progenitor cells (HPCs). Decreased HSCs/HPCs compromise their use in human and mouse hematopoietic cell transplantation (HCT) and gene therapy to correct genetic defects causing FA. We reported increased collection of HSCs from mouse bone marrow and mobilized peripheral blood, and human cord blood of normal donors after collection/processing in low (3%) oxygen (physioxia). We assessed comparative contents of long-term (LT)-HSCs from BM of fanca−/− and fancc−/− when collected/processed at 3% O2, in order to negate effects of extra physiological shock stress (EPHOSS) induced by collection/processing in ambient air. Collection/processing of BM from fanca−/− and fancc−/− mice in physioxia demonstrated a ≥3-fold increase in LT-HSCs compared to that in ambient air. This was associated with decreased phenotypic multipotential progenitor cells and functional granulocyte macrophage, erythroid, and multi-potential progenitors, results similar to that for BM from normal donor mice. Increased collection of HSCs could have clinical applicability for gene therapy and HCT.
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DOI：
10.1002/stem.3243
发表时间：
2020-10-01
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Broxmeyer HE;Cooper S;Capitano ML
通讯作者：
Capitano ML
DOI：
10.1016/j.bcmd.2020.102435
发表时间：
2020-09
期刊：
Blood cells, molecules & diseases
影响因子：
--
作者：
Capitano ML;Griesenauer B;Guo B;Cooper S;Paczesny S;Broxmeyer HE
通讯作者：
Broxmeyer HE
影响因子：
3.2
作者：
Broxmeyer HE;O'Leary HA;Huang X;Mantel C
通讯作者：
Mantel C
影响因子：
158.5
作者：
GLUCKMAN, E;BROXMEYER, HE;BOYSE, EA
通讯作者：
BOYSE, EA
影响因子：
20.3
作者：
Freie, B;Li, XX;Clapp, DW
通讯作者：
Clapp, DW