Hematopoietic Stem and Progenitor Cells (HSPCs) are foundational cells responsible for generating the entire blood and immune system. These immature cells possess the ability to develop into all specialized blood cell types. Understanding HSPCs involves recognizing their dual capacity to both self-renew and differentiate, continuously replenishing the body’s cellular components.
The Process of Hematopoiesis
The continuous production of blood cells is a biological function known as hematopoiesis. This process begins with a single hematopoietic stem cell, which can produce more of itself and give rise to all other blood cells. Hematopoietic stem cells reside primarily within the bone marrow, where they are nurtured in specialized microenvironments.
These self-renewing stem cells differentiate into specialized progenitor cells, forming specific blood cell lineages. These lineages include myeloid cells and lymphoid cells. Myeloid progenitors develop into red blood cells, which transport oxygen throughout the body, and platelets, which are cell fragments that facilitate blood clotting.
Myeloid progenitors also give rise to white blood cells, such as neutrophils, eosinophils, basophils, and monocytes, which play roles in the body’s immune response. Lymphoid progenitors differentiate into lymphocytes, specifically T cells and B cells, central to adaptive immunity. This process ensures a steady supply of new blood cells, maintaining overall health and protecting against infection.
Sources of Hematopoietic Stem Cells
HSPCs can be collected from several locations for medical applications. The primary source is the bone marrow, the spongy tissue found inside larger bones like the hip. Collection typically involves a surgical procedure where liquid marrow is aspirated directly from the bone.
Peripheral blood is another source, though it normally contains only a small number of HSPCs. To increase their presence for collection, donors receive specific medications, such as granulocyte colony-stimulating factor (G-CSF) or plerixafor. These drugs stimulate HSPCs to move from the bone marrow into the circulating blood, a process termed mobilization. The cells are then collected through apheresis, a non-surgical procedure that separates HSPCs from drawn blood, returning other components.
Umbilical cord blood, collected from the umbilical cord and placenta after birth, is a third source of HSPCs. This collection is non-invasive and poses no risk to the mother or baby. Cord blood units are cryopreserved and stored in blood banks for future use, offering an accessible option, especially for patients who may not have a suitable bone marrow or peripheral blood donor.
HSPC Transplantation in Medicine
HSPC transplantation, commonly known as a stem cell or bone marrow transplant, is an established medical procedure used to replace a patient’s diseased or damaged blood-forming system with healthy HSPCs. This approach treats various conditions, including blood cancers like leukemias, lymphomas, and multiple myeloma, as well as non-cancerous conditions such as aplastic anemia, immune system disorders, and inherited genetic blood disorders like sickle cell disease and beta-thalassemia.
Before transplantation, patients undergo conditioning regimens involving high-dose chemotherapy, sometimes combined with radiation. This treatment aims to eliminate diseased cells and suppress the immune system to prevent rejection of the new cells. Following conditioning, healthy HSPCs are infused into the bloodstream, where they travel to the bone marrow to engraft and produce new, healthy blood cells.
Transplants can be categorized into two types based on the cell source. An autologous transplant uses the patient’s own HSPCs, which are collected and stored before conditioning treatment, then reinfused. This approach avoids immune rejection issues. An allogeneic transplant, in contrast, uses HSPCs from a donor, a related family member or an unrelated volunteer. For allogeneic transplants, careful donor matching, primarily based on human leukocyte antigen (HLA) markers, minimizes the risk of immune complications like graft-versus-host disease.
Emerging Research and Therapeutic Potential
Beyond established transplantation, ongoing research explores advanced HSPC applications, particularly in gene therapy. Scientists are investigating gene-editing tools, such as CRISPR-Cas9, to correct genetic defects directly within a patient’s own HSPCs. This approach holds promise for treating inherited blood disorders like sickle cell disease and beta-thalassemia.
For example, in sickle cell disease, gene editing aims to reactivate fetal hemoglobin production or correct the mutation in the adult hemoglobin gene, preventing red blood cell sickling. The modified HSPCs are then reinfused into the patient, offering a potential one-time corrective treatment. Clinical trials show encouraging results, with some gene-edited HSPC therapies recently receiving regulatory approvals.
Another research area focuses on ex vivo expansion, involving growing large quantities of HSPCs in a laboratory. This seeks to overcome limitations like low cell numbers in umbilical cord blood units or challenges in collecting sufficient cells from donors. While challenges remain, including maintaining the stem cells’ ability to self-renew without unwanted differentiation, advancements in culture protocols using specific proteins and small molecules show progress.