Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

Abstract

Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers.

Acute Exercise in Hypobaric Hypoxia Attenuates Endothelial Shedding in Subjects Unacclimatized to High Altitudes

“…The authors' explanation for hypoxia-induced CPC reduction was an increase in CXCR-4 on the cells' surface helping them to quickly respond to a high expression of SDF-1α in peripheral tissues. Exercise-induced CPC concentrations at high altitude in our study were neither related to SDF-1α nor to IL-3 plasma concentrations, which would argue against the exercise-induced push-pull mechanism-local factors within the bone marrow niche "push" CPCs to the circulation, while systemic factors in blood "pull" CPCs from the bone marrow (Emmons et al, 2016). It is rather likely that CPC migration was triggered by tissue hypoxia, as shown after a 12-day trek at high altitude (Mancuso et al, 2008).…”

“…Different circulating proteins have been shown to modulate exercise-induced EC and CPC concentrations such as enzymes related to endothelial matrix remodeling [matrix metalloproteinases, (MMPs); tissue inhibitor of MMPs (TIMP)] (Ross et al, 2014) and hematopoietic cytokines [stromal cell-derived factor (SDF-1α); interleukin-3 (IL-3)] (Emmons et al, 2016). In detail, MMP-2 and MMP-9 are gelatinases, proteolytic enzymes secreted from many cell types such as ECs, monocytes, and macrophages (Newby, 2008) and are responsible for remodeling and degrading the basement membrane and endothelium upon leukocyte transendothelial migration via VCAM-1 (Cook-Mills, 2006).…”

Effects of endurance exercise training on inflammatory circulating progenitor cell content in lean and obese adults

“…To our knowledge, this is the first study to describe a reduction in the proportion and concentration of HSPCs following EET in both lean and obese adults. Discrepancies in the literature could be due to the lack of a consistent endurance exercise intervention (Emmons et al . 2016), variability in time of CPC/HSPC quantification following the most recent exercise bout (with some not specified) (Bonsignore et al .…”

Can yoga therapy stimulate stem cell trafficking from bone marrow?

“… A number of redundant pathways in the niche exist to mediate HSPC mobilization into peripheral circulation. By acute and chronic inflammatory stimuli – Acute exercise-induced inflammation may be a potential mechanism responsible for HSPC mobilization [16] . …”

“…By acute and chronic inflammatory stimuli – Acute exercise-induced inflammation may be a potential mechanism responsible for HSPC mobilization [16] .…”