For the first time, researchers have directly compared the extent to which intense physical exercise, as opposed to a drug, mobilizes blood stem cells for donation.
Image Credit: Scientific Frontline
Scientific Frontline: Extended "At a Glance" Summary: Stem Cell Mobilization via Physical Exercise
The Core Concept: Intense physical exercise, such as cycling, can rapidly mobilize hematopoietic stem cells into the bloodstream, serving as a potential adjunctive therapy to enhance stem cell donation procedures for conditions like leukemia.
Key Distinction/Mechanism: Unlike the standard medication (G-CSF), which takes several days to non-specifically release massive quantities of stem cells from the bone marrow, acute exercise rapidly dislodges a smaller but highly targeted yield of beneficial "early" stem cells and platelet precursors that adhere to blood vessel walls.
Major Frameworks/Components:
- Hematopoietic Stem Cells (HSCs): Self-renewing cells in the bone marrow capable of producing all types of blood and immune cells.
- Granulocyte Colony-Stimulating Factor (G-CSF): The standard pharmacological agent used to stimulate the bone marrow into releasing stem cells into the blood.
- Peripheral Blood Stem Cell (PBSC) Apheresis: The clinical process of extracting stem cells from a donor's circulating blood.
- Hemodynamic Mobilization: The mechanism by which increased blood flow and shear stress from exercise dislodge stem cells adhering to endothelial vessel walls.
Branch of Science: Hematology, Sports Medicine, Oncology, and Cellular Biology.
Future Application: Implementing "intra-apheresis cycling"—having donors perform interval cycling during the collection process—could be utilized in clinical settings to improve the quality of the immune graft and reduce the necessity for prolonged or repeated collection sessions.
Why It Matters: Enhancing stem cell yields through a low-risk, non-pharmacological intervention like exercise can improve both the donor experience and the success rates of transplants for patients battling blood cancers.
A blood stem cell donation can save the lives of people with leukemia. To collect these cells from the bloodstream, donors are given medication that mobilizes blood stem cells from the bone marrow. A pilot study now suggests that physical exercise could specifically support stem cell donation.
Blood stem cells in the bone marrow continuously produce new blood and immune cells. When this system becomes diseased, as in leukemia, a transplant of healthy stem cells from a compatible donor can offer a chance for a cure.
Before donating stem cells, donors receive the drug G-CSF, which mobilizes blood stem cells from the bone marrow so they can be collected from the blood. However, treatment with G-CSF is often associated with side effects, such as bone pain. In some cases, the number of stem cells collected is also insufficient, requiring additional treatment cycles and medication.
Previous studies have shown that intense physical exercise can likewise release blood stem cells into the bloodstream. Unlike additional medication, physical exercise is considered very low risk. PD Dr. Julia Kröpfl, together with a research team from the Department of Sport, Exercise, and Health at the University of Basel, therefore investigated this effect in a pilot study. For the first time, the researchers directly compared, in the same donors, how physical exercise and G-CSF mobilize blood stem cells.
Cycling for Stem Cell Donation
In collaboration with Professor Andreas Holbro, a senior physician at Blood Donation Northwest Switzerland and the Department of Hematology at the University Hospital Basel, the team recruited seven male and three female donors who were preparing to donate blood stem cells to family members. The participants first completed an intensive cycling session on an ergometer and provided blood samples before and after the exercise. A few days later, they underwent the conventional treatment with G-CSF.
The direct comparison revealed differences in both the quantity and the composition of the mobilized blood stem cells. Previous studies have shown that after an intense training session, the number of stem cells rises within minutes but then rapidly declines again. With G-CSF, by contrast, it takes several days for blood stem cell levels in the bloodstream to increase.
"The effect of acute physical exercise is small, but it is more targeted in terms of the composition of the mobilized cells." —PD Dr. Julia Kröpfl
In terms of the number of blood stem cells in the blood, physical exercise had a significantly smaller effect than the medication. The acute exercise stimulus increased stem cell numbers only moderately—to around 1.5 to 2 times the baseline levels. With G-CSF, however, stem cell levels increased 20- to 50-fold.
"The effect of acute physical exercise is small, but it is more targeted in terms of the composition of the mobilized cells," explains Kröpfl. G-CSF nonspecifically releases all subtypes of blood stem cells. Intense physical exercise, by contrast, specifically dislodged cells considered beneficial for a successful transplant. These include, for example, platelet precursor cells and less mature—essentially "early"—blood stem cells, which are thought to have a particularly high capacity to establish themselves in the recipient's body. What this means clinically for patients, however, remains unclear.
Not a Replacement, but a Promising Adjuvant
Previous analyses suggest that acute physical exercise primarily mobilizes blood stem cells that adhere to blood vessel walls, due to increased blood flow. This could explain the faster effect of exercise compared with the medication.
"Physical exercise cannot replace G-CSF treatment for stem cell donation, but it could potentially complement it." —PD Dr. Julia Kröpfl
"Physical exercise cannot replace G-CSF treatment for stem cell donation, but it could potentially complement it," emphasizes Kröpfl. "The combination of both approaches would be promising." While the drug releases stem cells from the bone marrow, physical exercise could additionally mobilize cells adhering to blood vessels, thereby complementing and potentially enhancing the effect of G-CSF.
Because of the small number of participants, the study provides only preliminary evidence that will need to be confirmed by further research. However, Kröpfl explains that a study combining G-CSF and cycling cannot currently be conducted in Switzerland for ethical reasons. There is too much uncertainty about whether physical exercise could worsen the side effects of G-CSF and potential complications during stem cell collection.
"However, it is entirely possible that exercise could actually alleviate these side effects, as has also been observed in patients undergoing chemotherapy," says the molecular biologist. A study in England is already investigating the combination of G-CSF and cycling.
Published in journal: European Journal of Applied Physiology
Authors: Elias Siebold, Laura Infanti, Hans-Jürgen Gruber, Gregor T. Stehle, Debbie Maurer, Egbert T. Ritter, Michael Medinger, Francesca Matteazzi, Arno Schmidt-Trucksäss, Andreas Holbro, and Julia M. Kröpfl
Source/Credit: University of Basel | Angelika Jacobs
Reference Number: med051226_01
.png)
.jpg)