Stem cell mobilization is a medical process that moves blood-forming cells from their natural location in the bone marrow into the bloodstream for collection. These hematopoietic stem cells (HSCs) are the precursors for all mature blood cells, including red cells, white cells, and platelets. HSCs primarily reside within the bone marrow, the spongy tissue found inside bones like the pelvis and sternum.
The bone marrow provides a specialized microenvironment, often called the hematopoietic niche, which supports the survival and self-renewal of HSCs. Mobilization temporarily disrupts the mechanisms that anchor these cells to the marrow, causing them to migrate into the circulating blood. This process makes the stem cells accessible for collection prior to therapeutic procedures.
The Necessity of Mobilizing Stem Cells
Mobilization is necessary because transplantation procedures require a large quantity of hematopoietic stem cells. Under normal conditions, the peripheral blood contains too few circulating stem cells for a successful transplant via a simple blood draw.
Historically, stem cells were harvested directly from the bone marrow through a surgical procedure called bone marrow aspiration. This method required general anesthesia and involved inserting large needles into the pelvic bone to withdraw the marrow. Mobilization provides a less invasive alternative by inducing the stem cells to move into the peripheral blood.
Increasing the number of stem cells in the peripheral blood allows collection to be an outpatient procedure, avoiding the risks and discomfort of surgery. This shift has largely replaced bone marrow as the primary source of stem cells for transplantation. The harvested cells are used to rescue a patient’s blood system after damage from high-dose chemotherapy or radiation, and collecting a higher dose leads to faster recovery of blood counts.
Pharmacological Agents Used in Mobilization
Pharmacological agents are administered to signal stem cells to leave the bone marrow niche. These agents interfere with the adhesion molecules and signaling pathways that keep the cells tethered to the marrow environment. The most common strategy uses a growth factor, often combined with a chemokine receptor blocker.
The primary agent is Granulocyte Colony-Stimulating Factor (G-CSF), a synthetic protein. G-CSF stimulates the production and maturation of neutrophils, which then release enzymes. These enzymes cleave molecules like CXCL12 and VCAM-1 responsible for stem cell retention in the bone marrow niche. Patients typically receive G-CSF as a subcutaneous injection for several days, which can cause mild bone pain as the marrow expands.
In patients with prior extensive chemotherapy exposure, G-CSF alone may not release enough stem cells. For these individuals, a second agent, Plerixafor, is often used. Plerixafor is a targeted drug that acts as a reversible antagonist of the CXCR4 receptor found on hematopoietic stem cells. This receptor normally binds to the chemokine SDF-1 (CXCL12) in the bone marrow, which acts like an anchor.
By blocking the SDF-1/CXCR4 interaction, Plerixafor rapidly disrupts the retention signal, causing a quick flush of stem cells into the peripheral blood, usually within hours. The combination of G-CSF’s prolonged stimulating effect and Plerixafor’s rapid action significantly increases the yield of collectible stem cells. This two-drug strategy is frequently used in patients with conditions like multiple myeloma and non-Hodgkin’s lymphoma to ensure successful collection.
The Process of Cell Collection (Apheresis)
The collection of mobilized stem cells is performed through a procedure called apheresis, sometimes referred to as leukapheresis. This process uses a specialized machine to filter stem cells directly from the patient’s circulating blood by separating blood components, similar to blood donation.
During apheresis, blood is continuously drawn from one intravenous line, often a central venous catheter or a large arm vein. The blood circulates through the machine, where it is spun in a centrifuge to separate components by weight. The layer containing the stem cells, known as the buffy coat, is collected into a sterile bag.
The remaining blood components, including red blood cells, plasma, and platelets, are returned to the patient through a separate intravenous line. The entire process is performed on an outpatient basis, usually taking three to five hours per session. Multiple sessions over one to three days may be required to collect the target number of cells needed for the transplant.
Monitoring the number of circulating stem cells is crucial, achieved by measuring the count of \(\text{CD}34^{+}\) cells. The \(\text{CD}34^{+}\) protein is a marker found on the surface of hematopoietic stem and progenitor cells. Daily blood samples are taken during mobilization to count these cells. A count exceeding a certain threshold, often 15 to 20 \(\text{CD}34^{+}\) cells per microliter of blood, indicates the optimal time to begin apheresis. This measurement is the strongest predictor of the final yield.
Primary Clinical Applications and Patient Factors
Mobilized stem cells are primarily used in high-dose therapy followed by a stem cell transplant to treat various cancers of the blood and immune system. Common applications include treating multiple myeloma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and certain types of leukemia. In these cases, the patient receives high-dose chemotherapy to destroy cancer cells, and the stored stem cells are reinfused to restore the damaged blood and immune system.
The procedure is also used for some non-cancerous conditions, such as autoimmune diseases, aplastic anemia, and certain solid tumors. For a successful transplant, a minimum of \(2 \times 10^6\) \(\text{CD}34^{+}\) cells per kilogram of the patient’s body weight must generally be collected.
Several patient-specific factors influence the success of mobilization. Age is a significant factor, as patients over 60 years old sometimes experience less successful mobilization. A patient’s history of prior treatments is also highly relevant, since extensive previous chemotherapy or radiation to bone-containing areas can damage the stem cell reserve and the marrow niche.
Other indicators for a poor yield include a low platelet count before mobilization, which suggests a limited bone marrow reserve, and the type of disease being treated. Patients with a history of receiving certain myelotoxic agents or multiple cycles of chemotherapy may require more aggressive mobilization strategies, such as the addition of Plerixafor, to reach the necessary cell count.