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Influence of physical fitness as donor-intrinsic factor on CD34+ graft composition and outcome in the recipient (StemCellFit)
Third-party funded project
Project title Influence of physical fitness as donor-intrinsic factor on CD34+ graft composition and outcome in the recipient (StemCellFit)
Principal Investigator(s) Kröpfl, Julia Maria
Organisation / Research unit Departement Sport, Bewegung und Gesundheit / Sportmedizin (Schmidt-Trucksäss)
Department Departement Sport, Bewegung und Gesundheit
Project start 01.09.2022
Probable end 31.12.2023
Status Completed
Abstract

Hematopoietic stem and progenitor cell (HPC) mobilization can be triggered by exogenous and endogenous triggers. G-CSF is commonly used as exogenous stimulant for HPC mobilization to treat hematological malignancies such as acute myeloid leukemia by HPC transplantation. Although established, there are still 2-5% healthy donors that cannot mobilize sufficient HPC. These HPC grafts are usually recovered with an additional dose of plerixafor. Nonetheless both pharmacological agents often show side effects. Furthermore, graft composition and transplantation outcome highly depend on the mobilization regimen used. CD34+ subgroups within a HPC graft are often not evenly affected by G-CSF mobilization. Although falling on the low end of the G-CSF spectrum, exhaustive physical exercise is a non-invasive endogenous trigger that also enhances HPCs in circulation by adrenergic signaling and shear stress. It could provide an interesting possibility as adjuvant therapy – especially because the response of the mature immune system is more favorable, it is non-invasive and has no side effects. Also, each exercise bout primes stem cells in bone marrow and with exercise training cells are less susceptible to physiological stressors, possibly also to exogenously applied G-CSF. A higher donor cardiorespiratory fitness (CRF), similar to a lower age, could positively influence CD34+ graft composition and possibly also transplantation outcome. Recent literature supports the notion of donor-intrinsic factors dictating mobilization response. The aims of this study will be a) to assess the degree to which CRF contributes to the number and viability (apoptosis and autophagy) of agent- or acute exercise-induced CD34+ cells and their subgroups, b) to investigate if a HPC graft from a fitter donor positively influences CD34+ transplantation outcome in the recipient and c) to compare the effects of both exogenous and endogenous mobilization regimens in terms of CD34+ subgroup numbers and cell viability in the same related donors. Cell counting will be investigated by flow cytometry and a hematology analyzer, and CRF by an exhaustive incremental test, a fitness questionnaire and accelerometer analysis over 7-days. Results will provide more knowledge about donor-intrinsic factors influencing CD34+ subgroup mobilization by pharmacological agents in related donors and CD34+ outcome in respective recipients. Furthermore, exogenous and endogenous HPC mobilization will be compared in the same donors. This study will provide the basis for a future clinical exploration of acute exercise in a related donor transplantation setting.

Financed by University of Basel
   

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22/05/2024