Abstract
Effects of tobacco smoke on hematologic derangements have received little attention. This study employed a mouse model of cigarette smoke exposure to explore the effects on bone marrow niche function. While lung cancer is the most widely studied consequence of tobacco smoke exposure, other malignancies, including leukemia, are associated with tobacco smoke exposure. Animals received cigarette smoke exposure for 6 h/day, 5 days/week for 9 months. Results reveal that the hematopoietic stem and progenitor cell (HSPC) pool size is reduced by cigarette smoke exposure. We next examined the effect of cigarette smoke exposure on one supporting cell type of the niche, the mesenchymal stromal cells (MSCs). Smoke exposure decreased the number of MSCs. Transplantation of naïve HSPCs into irradiated mice with cigarette smoke exposure yielded fewer numbers of engrafted HSPCs. This result suggests that smoke-exposed mice possess dysfunctional niches, resulting in abnormal hematopoiesis. Co-culture experiments using MSCs isolated from control or cigarette smoke-exposed mice with naïve HSPCs in vitro showed that MSCs from cigarette smoke-exposed mice generated marked expansion of naïve HSPCs. These data show that cigarette smoke exposure decreases in vivo MSC and HSC number and also increases pro-proliferative gene expression by cigarette smoke-exposed MSCs, which may stimulate HSPC expansion. These results of this investigation are clinically relevant to both bone marrow donors with a history of smoking and bone marrow transplant (BMT) recipients with a history of smoking.
Highlights
While pulmonary disorders are the most obvious manifestation of cigarette smoke-induced disease, there is a growing appreciation that smoking and chronic lung disease are associated with significant systemic consequences and comorbidities
The current study examined the effects of cigarette smoke exposure on hematopoietic stem and progenitor cells (HSPCs) and on the hematopoietic stem cell niche in the bone marrow
We found that smoke exposure decreased HSPCs and showed a trend for decreased long-term repopulating hematopoietic stem cells (LT-HSCs), as defined by lineage (Lin)-c-kit+stem cell antigen-1 (Sca-1)+ (LKS) and signaling lymphocyte activation molecule (SLAM; Lin-CD48-CD150+) marker phenotypes, respectively [10,11]
Summary
While pulmonary disorders are the most obvious manifestation of cigarette smoke-induced disease, there is a growing appreciation that smoking and chronic lung disease are associated with significant systemic consequences and comorbidities. Circulating endothelial and hematopoietic progenitors are reduced in chronic obstructive pulmonary disease patients with low body mass index, suggesting that systemic disease is related to stem cell function [2]. Despite the egress of maturing cells from the bone marrow, several studies have found fewer circulating CD34+ progenitor/stem cells in both smokers and patients with chronic lung disease [2,4,5,6]. Limited and conflicting data, using colony forming assays for hematopoietic progenitors, are available describing the effects of cigarette smoke and its constituents on bone marrow stem cells [7,8]. We hypothesized that chronic smoke exposure decreases the bone marrow HSPC pool by perturbing the stem cell niche in a murine model. The results of this study may impact both bone marrow donors and BMT recipients
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