Haematopoietic stem cells (HSCs) are multipotent progenitor cells that give rise to all the cellular components of blood: red blood cells, white blood cells and platelets. Located primarily in the bone marrow, they form the basis of the haematopoiesis process and constitute one of the most relevant therapeutic resources in modern medicine, from the treatment of leukaemias to the possible cure of serious hereditary diseases.
What are haematopoietic stem cells: definition and characteristics
Haematopoietic stem cells are undifferentiated cells possessing two unique properties: the capacity for self-renewal —dividing whilst producing new cells with identical potential— and the capacity to differentiate into all blood cell lineages. This duality makes them the cornerstone of the haematopoietic system throughout an individual’s entire life.
At the molecular level, HSCs express the surface antigen CD34 as a characteristic marker, although more primitive subpopulations also express CD133 and are negative for CD38. According to data gathered by the Instituto de Salud Carlos III (ISCIII), the precise identification of these subpopulations is essential to guarantee the quality of the cellular product in transplant protocols.
Morphologically, they are small cells with a large nucleus and scant cytoplasm, practically indistinguishable under the optical microscope from other haematopoietic precursors. Consequently, their identification requires multiparametric flow cytometry methods and immunophenotyping with specific antibody panels.
Haematopoiesis: the process HSCs sustain every day
Haematopoiesis is the continuous process by which the body generates and renews its blood cells. Haematopoietic stem cells are the cell of origin for this entire cascade. It is estimated that approximately 2 × 10¹¹ erythrocytes and 10¹⁰ leucocytes are produced each day in a healthy adult, a figure that can multiply several times under conditions of infection, haemorrhage or metabolic stress.
The process unfolds in distinct stages:
- Long-term HSCs (LT-HSCs) generate short-term HSCs (ST-HSCs) via asymmetric divisions.
- ST-HSCs give rise to common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs).
- These progenitors differentiate into mature cell types: erythrocytes, neutrophils, platelets, B lymphocytes, T lymphocytes and NK cells, amongst others.
HSCs reside in a specialised niche within the bone marrow —the endosteal niche and the vascular niche— which regulates their quiescence, proliferation and mobilisation through signals from transcription factors such as RUNX1, GATA-2, SCL/TAL1 and Meis1, as well as signalling pathways such as Wnt, Notch and Hedgehog.
Table 1. Cells of the haematopoietic lineage and their main function
| Cell type | Lineage | Main function |
|---|---|---|
| Erythrocytes | Erythroid lineage | Oxygen transport to tissues |
| Platelets (thrombocytes) | Megakaryocytic lineage | Coagulation and haemostasis |
| Neutrophils | Myeloid lineage | First line of antibacterial defence |
| B lymphocytes | Lymphoid lineage | Antibody production |
| T lymphocytes | Lymphoid lineage | Cellular immunity and regulation |
| NK cells | Lymphoid lineage | Destruction of tumour and infected cells |
| Macrophages | Myeloid lineage (monocytes) | Phagocytosis and antigen presentation |
Where haematopoietic stem cells are found in the body
Haematopoietic stem cells are not distributed homogeneously throughout the body. In adults, their main reservoir is the bone marrow, where they represent approximately 1% of total nucleated cells. In peripheral blood they circulate at much lower proportions, between 0.01% and 0.1%, although this percentage can increase significantly through pharmacological mobilisation.
Bone marrow
The bone marrow of flat bones such as the sternum, iliac crests and vertebrae houses the highest concentration of HSCs in the adult. The medullary niche regulates the quiescence of these cells through direct contact with osteoblasts and endothelial cells.
Umbilical cord blood
Umbilical cord blood is exceptionally rich in haematopoietic stem cells, with a CD34+ content far higher than that of adult blood. Its collection is straightforward, painless and risk-free for the mother or newborn. Since the 1980s, umbilical cord banks have stored these cells for autologous or allogeneic use. Ambar Lab offers specialised tests for stem cell cytogenetics from these sources.
Mobilised peripheral blood
In a clinical context, stimulating factors such as G-CSF (granulocyte colony-stimulating factor) or the CXCR4 antagonist Plerixafor are administered to release HSCs from the marrow into the bloodstream. Subsequent collection via apheresis allows a sufficient number of progenitors to be obtained for transplantation without the need for invasive marrow extraction.
Types of haematopoietic stem cells
Within the HSC population there exists a functional hierarchy based on self-renewal capacity and period of activity:
- Long-term HSCs (LT-HSCs): maximum self-renewal capacity. They can permanently reconstitute the haematopoietic system. They are the most primitive and represent only 0.01% of bone marrow cells.
- Short-term HSCs (ST-HSCs): time-limited self-renewal capacity (weeks). They generate a high number of progenitors before being exhausted.
- Multipotent progenitors (MPPs): these are no longer strictly “stem cells” in the classical sense but maintain multipotency; they constitute the transition towards specialised lineages.
The distinction between these stages is relevant in the context of haematopoietic stem cell transplantation: the ideal product must contain a sufficient number of LT-HSCs to ensure permanent donor engraftment in the recipient.
Clinical applications: HSC transplantation and diseases treated
Haematopoietic stem cell transplantation (also called bone marrow transplantation when the source is medullary) is the reference therapeutic procedure for a broad spectrum of conditions. According to data from the European Bone Marrow Transplantation Registry (EBMT), in 2023 more than 47,000 HSC transplants were performed in Europe, with a growing trend year on year.
Malignant haematological diseases
- Acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML)
- Acute lymphoblastic leukaemia (ALL)
- Hodgkin’s lymphoma and refractory non-Hodgkin’s lymphomas
- Multiple myeloma
- High-risk myelodysplastic syndromes
Non-malignant diseases
- Severe aplastic anaemia
- Sickle cell anaemia and major thalassaemias
- Severe combined immunodeficiency (SCID)
- Hurler syndrome and other lysosomal storage diseases
- Certain forms of refractory multiple sclerosis and rheumatoid arthritis (investigational use)
Transplantation may be autologous (using the patient’s own HSCs, re-infused after high-dose chemotherapy) or allogeneic (using HSCs from an HLA-compatible donor). Allogeneic transplantation adds the benefit of the graft-versus-tumour (GVT) effect, although it carries the risk of graft-versus-host disease (GvHD), a complication requiring specialist follow-up.
How haematopoietic stem cells are obtained and mobilised
There are three main procedures for obtaining HSCs for therapeutic purposes:
Bone marrow aspiration
This is the classical technique: under general or epidural anaesthesia, between 500 and 1,000 ml of bone marrow are extracted from the iliac crest. It requires a brief hospital stay and entails postural discomfort for a few days.
Apheresis of mobilised peripheral blood
Following administration of G-CSF for 4–5 days (with or without Plerixafor in refractory cases), HSCs migrate to the peripheral blood and are collected by leukapheresis. This is now the most widely used source in autologous transplantation and increasingly in allogeneic transplantation from adult donors.
Umbilical cord blood
Collection occurs at the time of delivery, from the residual blood in the cord. The sample is cryopreserved and can be stored for decades without significant loss of viability. Its main limitation is cell number, which may require the use of two units in heavier patients.
At Ambar Lab we carry out quality control on all these sources. If you require information on cell line control analyses, visit our haematopoietic stem cell cytogenetics page, where you will find the services available for R&D institutions and hospital centres.
Cytogenetics as a quality control tool in HSCs
One of the least visible but critical consequences of prolonged culture of haematopoietic stem cells is chromosomal instability: variations in the number or structure of chromosomes that may compromise the safety of the cellular product or alter the behaviour of the lines under study.
Stem cell karyotyping —also known as conventional G-banding cytogenetics— enables detection of these abnormalities with a resolution of several megabases. For submicroscopic anomalies or post-transplant chimerism monitoring, microsatellite analysis via QF-PCR and fragment analysis is employed, offering greater sensitivity and speed.
These tests are particularly relevant in:
- Clinical trials involving HSC-based gene therapy.
- Post-allogeneic transplant chimerism monitoring to assess engraftment success.
- Quality control of hiPSC lines (human induced pluripotent stem cells) prior to differentiation.
- Basic research in haematopoietic developmental biology.
Ambar Lab is an international reference laboratory in applied cytogenetics. You can consult our complete catalogue of specialised tests or find out more about our R&D collaborations in clinical research.
Research frontiers: gene editing and advanced therapies
The field of haematopoietic stem cells is undergoing rapid transformation thanks to convergence with gene editing tools. CRISPR-Cas9 technology allows mutations to be corrected directly in the patient’s HSCs before re-infusion, without the need for a donor. In 2023, the FDA approved the first gene therapies based on edited HSCs for sickle cell anaemia and beta-thalassaemia, marking a historic milestone in the field.
Ex vivo expansion of HSCs
One of the historic challenges in cord blood transplantation is the low cell number. Current research focuses on ex vivo expansion of HSCs using thrombopoietin receptor agonists (SR1), HDAC inhibitors, or molecules such as UM171, which maintain “stemness” during the expansion process without inducing premature differentiation.
Haematopoietic stem cells and autoimmune diseases
Beyond oncohematology, HSC transplantation is being actively investigated in primary progressive multiple sclerosis, refractory lupus and type 1 diabetes. The idea is to “reset” the immune system by eradicating autoreactive clones and rebuilding tolerance with the new graft.
According to the Spanish Society of Haematology and Haemotherapy (SEHH), clinical trials in this area are expanding across several Spanish centres, with promising results in long-term quality of life.
Frequently asked questions about haematopoietic stem cells
What exactly are haematopoietic stem cells?
Haematopoietic stem cells are multipotent progenitor cells responsible for generating all the cellular components of blood: erythrocytes, leucocytes and platelets. They reside primarily in the bone marrow and are identified by the surface marker CD34.
Where are they found in the body?
They are located primarily in the bone marrow (1% of total nucleated cells), but also circulate in peripheral blood (0.01–0.1%) and are present at high concentration in umbilical cord blood at the time of delivery.
For which diseases are HSC transplants used?
They are used primarily in leukaemias, lymphomas, multiple myeloma, sickle cell anaemia, thalassaemia and severe combined immunodeficiency. They also have growing application in refractory autoimmune diseases.
What is the difference between autologous and allogeneic transplantation?
In autologous transplantation, the patient’s own cells are used, eliminating the risk of rejection. In allogeneic transplantation, cells from a compatible donor are used, with a greater antitumour effect but also a higher risk of graft-versus-host disease (GvHD).
What is haematopoiesis?
Haematopoiesis is the continuous process of blood cell formation. HSCs are the cell of origin for this entire cascade: they generate around 2 × 10¹¹ erythrocytes and 10¹⁰ leucocytes each day to maintain blood homeostasis.
Which laboratory tests are used to monitor HSCs?
The most common are stem cell karyotyping to detect chromosomal instability, flow cytometry immunophenotyping (CD34, CD133 markers) and microsatellite analysis via QF-PCR for monitoring cell lines in culture.
Can umbilical cord blood be stored?
Yes. Umbilical cord blood is a very rich source of HSCs and can be stored in public or private banks. Collection is painless and risk-free, and stored cells maintain their viability for decades thanks to cryopreservation in liquid nitrogen.
What is the marker that identifies HSCs?
The CD34 marker is the principal identifier in clinical practice. In research, CD133, CD38− and CD90 are also used to characterise subpopulations with different self-renewal capacities.
HSCs: at the centre of regenerative medicine
Haematopoietic stem cells represent one of the most well-established therapeutic assets and, at the same time, one of the fields with the greatest future potential in biomedicine. From the first bone marrow transplant performed by Dr E. Donnall Thomas in 1956 —recognised with the Nobel Prize in Medicine in 1990— to the gene therapies approved in 2023, the journey has been remarkable and continues to accelerate.
For hospital centres, research groups and laboratories working with these cells, rigorous cytogenetic quality control is an indispensable guarantee of quality and safety. At Ambar Lab we offer the specialised analyses you need: from stem cell karyotyping to post-transplant chimerism monitoring.
Are you working with HSC lines or collaborating on clinical trials? Contact our scientific team and discover how Ambar Lab can be your reference laboratory.
