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Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function
Maegan L. Capitano, … , Christie M. Orschell, Hal E. Broxmeyer
Maegan L. Capitano, … , Christie M. Orschell, Hal E. Broxmeyer
Published January 4, 2021
Citation Information: J Clin Invest. 2021;131(1):e140177. https://doi.org/10.1172/JCI140177.
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Research Article Aging Hematology

Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function

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Abstract

Bone marrow (BM) hematopoietic stem cells (HSCs) become dysfunctional during aging (i.e., they are increased in number but have an overall reduction in long-term repopulation potential and increased myeloid differentiation) compared with young HSCs, suggesting limited use of old donor BM cells for hematopoietic cell transplantation (HCT). BM cells reside in an in vivo hypoxic environment yet are evaluated after collection and processing in ambient air. We detected an increase in the number of both young and aged mouse BM HSCs collected and processed in 3% O2 compared with the number of young BM HSCs collected and processed in ambient air (~21% O2). Aged BM collected and processed under hypoxic conditions demonstrated enhanced engraftment capability during competitive transplantation analysis and contained more functional HSCs as determined by limiting dilution analysis. Importantly, the myeloid-to-lymphoid differentiation ratio of aged BM collected in 3% O2 was similar to that detected in young BM collected in ambient air or hypoxic conditions, consistent with the increased number of common lymphoid progenitors following collection under hypoxia. Enhanced functional activity and differentiation of old BM collected and processed in hypoxia correlated with reduced “stress” associated with ambient air BM collection and suggests that aged BM may be better and more efficiently used for HCT if collected and processed under hypoxia so that it is never exposed to ambient air O2.

Authors

Maegan L. Capitano, Safa F. Mohamad, Scott Cooper, Bin Guo, Xinxin Huang, Andrea M. Gunawan, Carol Sampson, James Ropa, Edward F. Srour, Christie M. Orschell, Hal E. Broxmeyer

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Figure 4

Numbers of functional HPCs from young and old C57BL/6 mouse BM collected under hypoxia and processed under ambient air or hypoxic conditions.

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Numbers of functional HPCs from young and old C57BL/6 mouse BM collected...
BM cells were collected and processed as in Figure 1A. Nucleated BM cells were used in an HPC CFU assay stimulated in vitro with EPO, SCF, PWMSCM, and hemin (A, C, and E) and cultured at 5% O2, with the percentage of HPCs in S-phase defined by a high specific activity tritiated thymidine kill assay (B, D, and F). The numbers of CFU-GM (A and B), BFU-E (C and D), and CFU-GEMM (E and F) were calculated per femur. Data represent the SEM for 10 C57BL/6 mice from 3–4 experiments. **P < 0.01 and ***P < 0.001, by 1-way ANOVA with post hoc Tukey’s multiple-comparison test.
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ISSN: 0021-9738 (print), 1558-8238 (online)

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