Stem cells serve as the body’s natural repair system due to their unique ability to develop into many different cell types. They are either pluripotent, meaning they can become nearly any cell in the body, or multipotent, restricting their differentiation to a specific tissue lineage, such as blood or bone. Stem cell therapy harnesses these capabilities, often by replacing damaged cells or stimulating the body’s own repair mechanisms. Administering this therapy is a highly regulated, multi-step procedure, extending from the initial cell source to the patient’s post-treatment recovery.
Harvesting and Collection Methods
Stem cells are obtained from either the patient’s own body (autologous source) or a compatible donor (allogeneic source). Autologous cells virtually eliminate the risk of immune rejection since they are genetically identical to the recipient’s cells. However, their availability and quality may be limited by the patient’s underlying condition. Allogeneic cells from a healthy donor can be produced in large quantities and are often necessary when the patient’s own cells are diseased or insufficient.
Bone marrow aspiration is a traditional collection method, typically harvesting hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) from the hip bone (posterior superior iliac crest). The procedure is performed under local or general anesthesia, inserting a hollow needle into the bone to draw out the liquid marrow. To maximize the stem cell count, the clinician must aspirate small volumes from multiple locations within the bone.
Peripheral blood stem cell collection is often preferred for its less invasive nature and relies on apheresis. The donor receives daily subcutaneous injections of a mobilization drug, such as granulocyte colony-stimulating factor (G-CSF), for several days prior to collection. G-CSF forces stem cells to leave the bone marrow and circulate, increasing the concentration of CD34+ cells in the peripheral blood. During apheresis, blood is drawn from a vein, passed through a machine that separates the stem cells, and the remaining components are returned to the donor.
Umbilical cord blood is another important allogeneic source, collected immediately after birth once the cord is clamped and cut. This collection is non-invasive and painless for the mother and infant, involving inserting a needle into a cord vein to allow blood to flow into a collection bag. Cord blood is rich in HSCs that are “immunologically young,” making them less likely to trigger a severe immune reaction in an unrelated recipient. The collected unit is then transported to a cord blood bank for processing and long-term storage.
Cell Preparation and Quality Control
Once collected, the cellular product undergoes rigorous laboratory steps before administration. Preparation begins with separation, filtering, and concentration to isolate the desired stem cell population, such as CD34+ cells for hematopoietic transplants. For certain therapies, particularly those using MSCs, the cells may be cultured and expanded in a laboratory environment to achieve the high cell count required for treatment.
For long-term storage, the cells are cryopreserved (frozen) using a controlled rate to prevent cell membrane damage. A cryoprotectant agent, typically dimethyl sulfoxide (DMSO), is added before the cells are slowly frozen and stored in liquid nitrogen vapor below -140°C. Immediately before transplantation, the frozen product is rapidly thawed in a 37°C water bath. The cryoprotectant is often removed to minimize potential toxicity in the patient.
Quality control is required throughout the entire process to ensure the product is safe and effective. Testing protocols include enumerating the total number of nucleated cells and the viable CD34+ cell count, which marks hematopoietic potency. Viability testing, often requiring a minimum threshold of 60% post-thaw, ensures the cells survived the freezing process. The product is also subjected to sterility screening for bacterial and fungal contamination to protect the patient from infection.
Routes of Therapeutic Delivery
The method for introducing prepared stem cells is tailored to the specific disease or target tissue, aiming to get the cells as close as possible to the site of injury. The most common and least invasive route for blood-related conditions, such as leukemia, is intravenous (IV) infusion. This method is similar to a standard blood transfusion, where the cell product is slowly dripped into a vein, allowing the cells to circulate throughout the body.
For hematopoietic stem cell transplantation, the infused cells naturally migrate, or “home,” to the bone marrow to repopulate the blood-forming system. For other conditions, the IV route allows mesenchymal stem cells to reach sites of inflammation or injury systemically, guided by biochemical signals from the damaged tissue. The entire infusion process typically takes 30 to 60 minutes.
Systemic infusion is not always effective, as only a small percentage (sometimes 1% to 5%) of the cells may engraft at the target site. This low retention rate necessitates localized delivery for conditions requiring a high concentration of cells in a specific area, such as orthopedic or cardiac repair. Direct injection involves using a syringe to administer the cells straight into the affected tissue, such as an arthritic joint (intra-articular) or damaged heart muscle.
More complex localized methods include surgical implantation or catheter-based delivery, used to target difficult-to-reach organs or the central nervous system. For neurological disorders, an intrathecal injection delivers cells directly into the spinal canal’s cerebrospinal fluid via a lumbar puncture. This bypasses the blood-brain barrier, allowing cells to reach the brain and spinal cord more effectively. Cell dosage is calculated based on the patient’s body weight and the type of disease, often aiming for a specific number of CD34+ cells per kilogram of body weight.
Immediate Post-Treatment Care
Following stem cell administration, patients are closely monitored for immediate reactions. Healthcare providers observe for acute adverse events during or shortly after the infusion, such as allergic responses to the cryoprotectant DMSO or signs of fluid overload. These reactions are typically managed promptly with supportive care and medication.
For patients receiving a transplant for blood disorders, the focus shifts to engraftment, where transplanted cells settle in the bone marrow and begin producing new, healthy blood cells. This process typically takes two to six weeks, during which the patient’s blood counts are checked frequently. Until engraftment is complete, the patient is at high risk of infection and bleeding due to low white blood cell and platelet counts, requiring preventative antibiotics and transfusions.
For allogeneic transplants, immunosuppressive drugs are given as prophylaxis to prevent the recipient’s immune system from rejecting the foreign cells. These medications also mitigate the risk of graft-versus-host disease (GVHD), a serious complication where the donor’s immune cells attack the patient’s tissues (e.g., skin, liver, or gut). Successful engraftment is confirmed by testing for hematopoietic chimerism, which determines the ratio of donor to recipient cells in the blood and bone marrow.