Hematopoietic stem cells (HSCs), also called blood-forming stem cells, make every type of blood cell: red blood cells that carry oxygen, platelets that help blood clot, and the white blood cells of the immune system. In adults they live in small numbers in the bone marrow, where they renew themselves and keep the blood system supplied throughout life.[1] A hematopoietic cell transplant (HCT) gives a patient these cells, from the patient or from a donor, to replace all or part of the patient’s blood-forming system. The cells can come from bone marrow, from blood after the stem cells have been moved out of the marrow with medicine, or from umbilical cord blood.[2]
Hematopoietic Cells from Bone Marrow | VIDEO
Blood is one of the fastest-renewing tissues in the body. An estimate that combined the number and lifespan of every major human cell type found that about 330 billion cells are replaced each day, and that close to 90 percent of them are blood cells.[3] Hematopoiesis, the making of blood, keeps up with this loss. HSCs are adult (somatic) stem cells. They can renew themselves, and they sit at the top of a hierarchy of progenitor cells that differentiate step by step into precursors of single cell types, which make red blood cells, megakaryocytes (the cells that release platelets), myeloid white cells and lymphocytes.[1]
Laboratories recognise blood stem cells by the proteins on their surface. The small population of blood cells that carry a protein called CD34 is thought to be responsible for rebuilding all the blood cell lines after a transplant, so a collection is checked by counting its CD34-positive cells with a flow cytometer. The International Society of Hematotherapy and Graft Engineering published a standard method for this count in 1996.[4]
Where Transplant Stem Cells Come From
Three sources are used for transplants.[2] In Europe in 2023, peripheral blood was the source for 83.9 percent of transplants from donors, bone marrow for 14.8 percent and cord blood for 1.3 percent.[5]
| Source | How it is collected | Points to know |
|---|---|---|
| Bone marrow | Drawn with a needle from the hip bone (the iliac crest) under anesthesia | Donors most often report back or hip pain at the collection site; median recovery is 3 weeks[6] |
| Peripheral blood | Daily injections of G-CSF (filgrastim), usually for 5 days, one of the cytokines that regulate blood cell production, move stem cells from the marrow into the blood; a machine then collects them by apheresis[7] | Nearly all donors have bone pain during the injections; median recovery is 1 week[6][8] |
| Umbilical cord blood | Taken from the blood vessels of the placenta and umbilical cord after birth and stored in a cord blood bank[9] | Fewer cells per unit; less graft-versus-host disease, so partly matched units can be used; slower recovery of blood counts and immunity, which can lead to infections[10] |
Placental blood and cord blood are the same thing: the blood left in the placenta and cord after delivery.[9] The placenta and amniotic membranes also contain other, non-blood-forming cell types, which are described on our page on placenta-derived stem cells. How the collection machine works is explained on our page on apheresis.
Peripheral blood and bone marrow were compared directly in a phase 3 randomized trial of 551 patients receiving cells from unrelated donors. Survival at 2 years did not differ significantly (51 percent with blood stem cells, 46 percent with marrow). Graft failure was less common with blood stem cells (3 percent against 9 percent), but chronic graft-versus-host disease was more common (53 percent against 41 percent).[7] Among unrelated donors of blood stem cells studied prospectively, 6 percent had severe short-term side effects, 0.6 percent had serious unexpected ones, and all recovered completely.[8]
Fat tissue is not one of these sources: the cells taken from it, the stromal vascular fraction, are not used for blood stem cell transplants.[2] Making transplantable blood stem cells from embryonic stem cells or induced pluripotent stem cells is still laboratory research: in 2017, scientists first guided human pluripotent stem cells to become blood-forming endothelium (vessel-lining cells able to give rise to blood), then converted these into blood stem and progenitor cells with seven transcription factors; the resulting cells produced myeloid cells, B cells and T cells after transplantation into mice.[11]
Autologous and Allogeneic Transplants
In an autologous transplant, the patient’s own stem cells are collected and stored, then given back after high-dose treatment. In an allogeneic transplant, the cells come from another person: a brother or sister, an unrelated volunteer from a donor registry, a half-matched (haploidentical) family member, or a cord blood unit.[2] The match that matters is in the HLA genes, which code for the tissue-type proteins that donor immune cells can recognise as foreign.[12] A well-matched unrelated donor is identical at ten HLA alleles (HLA-A, -B, -C, -DRB1 and -DQB1). Half-matched family transplants are now done mainly with high doses of cyclophosphamide given a few days after the transplant to prevent graft-versus-host disease, which has reduced chronic graft-versus-host disease and deaths from the transplant in this setting.[2]
| Feature | Autologous | Allogeneic |
|---|---|---|
| Source of cells | The patient | A matched or partly matched donor, or cord blood |
| Main purpose | Restores blood production after high-dose chemotherapy[13] | Replaces a diseased or failed marrow and adds a donor immune system that can attack leukemia cells[14] |
| Graft-versus-host disease | Does not occur in the usual form, because there are no donor immune cells | A main risk[12] |
| Main uses in Europe, 2023 (47,731 transplants from 696 centres, 57.1% of them autologous)[5] | Myeloma and other plasma cell disorders (58.2 percent), lymphomas (32.2 percent) | Myeloid cancers (60.7 percent), lymphoid cancers (25.0 percent), non-cancerous disorders (13.2 percent) |
The donor’s immune cells are part of how an allogeneic transplant works. In a registry study of 2,254 people given marrow from a matched sibling for leukemia, relapse was less common in those who developed graft-versus-host disease and more common after transplants from an identical twin or after removing T cells from the graft, evidence of a graft-versus-leukemia effect.[14]
How a Transplant Is Done
Before the infusion, the patient receives conditioning: chemotherapy, sometimes with radiation, to destroy the disease, make room in the marrow and, for donor cells, suppress the immune system enough to prevent rejection. Conditioning is classed by intensity. Myeloablative conditioning destroys the marrow permanently, so stem cell support is mandatory. Non-myeloablative conditioning causes only mild drops in blood counts. Reduced-intensity conditioning lies in between. Gentler regimens were developed to make donor transplants possible for older patients and those with other illnesses; with them, the benefit relies more on the donor cells’ effect against the cancer than on the conditioning itself.[15]
The stem cells are then given through a vein, like a blood transfusion. They travel to the bone marrow and begin making new blood cells, a step called engraftment. Until the new marrow works, the patient has very low blood counts and needs transfusions and protection from infection. In a 68-patient study of half-matched family marrow transplants, for example, the median time to recovery of infection-fighting neutrophils was 15 days and of platelets 24 days.[16]
What Transplants Treat
The worldwide transplant network counts the first transplant in 1957, almost 10,000 by 1985 and an estimated one million by December 2012.[17] Professional societies publish lists of indications and grade each one. The American Society for Transplantation and Cellular Therapy grades them from standard of care, through developmental, to not generally recommended.[18] The European Society for Blood and Marrow Transplantation (EBMT) uses standard of care, clinical option, developmental and generally not recommended.[2] Whether a transplant is right for one person also depends on the disease stage, the patient’s age and health, the donor and the other treatments available.
- Blood cancers. These account for most transplants: in Europe in 2023, myeloid cancers such as acute myeloid leukemia and lymphoid cancers were the main reasons for donor transplants, and myeloma and lymphomas for autologous ones.[5] In a phase 3 trial of 700 adults with newly diagnosed myeloma, adding high-dose melphalan with an autologous transplant to modern drug therapy lengthened median progression-free survival from 36 to 50 months, but overall survival at 4 years did not differ (81 and 82 percent).[13]
- Marrow failure. Newly diagnosed severe aplastic anemia with a matched sibling donor is a standard indication in adults, and in children severe aplastic anemia and inherited marrow failure syndromes are standard indications for a transplant from a matched sibling or well-matched unrelated donor.[2]
- Inherited blood disorders. A transplant from a matched brother or sister is the treatment of choice for young patients with transfusion-dependent beta thalassemia.[2] An international expert panel reported in 2014 that more than 90 percent of patients with thalassemia major or sickle cell disease survive the transplant and about 80 percent are free of disease afterwards.[19] In the United States, gene therapies made from a patient’s own blood stem cells are now also approved for transfusion-dependent beta thalassemia (ZYNTEGLO and CASGEVY).[20][21]
- Immune deficiencies and inherited metabolic disorders. Severe combined immunodeficiency, primary hemophagocytic lymphohistiocytosis, Hurler syndrome (MPS-1H) and osteopetrosis are among the standard indications in children.[2]
- Autoimmune diseases. EBMT counts autologous transplants as a standard of care for highly active relapsing multiple sclerosis that has not responded to disease-modifying treatment and for systemic sclerosis, and as a clinical option for selected patients with several other autoimmune diseases. For type 1 diabetes it lists autologous transplant as developmental, to be done only within research protocols.[2]
Heart failure is not among the EBMT indications for a blood stem cell transplant.[2]
Graft-Versus-Host Disease and Other Risks
Graft-versus-host disease (GVHD) happens when donor immune cells attack the patient’s tissues. Acute GVHD typically causes a skin rash, jaundice from damage to small bile ducts in the liver, nausea, and diarrhea with cramping. Between 30 and 50 percent of people who receive a donor transplant develop acute GVHD, and 14 percent develop the severe forms (grades III to IV).[12] Risk is higher with HLA mismatch, unrelated donors, female donors for male patients, blood stem cell grafts and more intense conditioning. Most patients receive preventive medicines, often a calcineurin inhibitor such as ciclosporin with methotrexate, and acute GVHD is treated first with corticosteroids. When steroids fail, the outlook is poor, with long-term survival of only 5 to 30 percent.[12]
Treatment for steroid-refractory acute GVHD has improved. In a phase 3 trial of 309 patients aged 12 or older, the JAK inhibitor ruxolitinib produced a response at day 28 in 62 percent, against 39 percent with the doctor’s choice of other treatments; median overall survival was 11.1 against 6.5 months, a difference that was not statistically significant.[22] On 18 December 2024 the US Food and Drug Administration approved remestemcel-L (Ryoncil), made from donated bone marrow mesenchymal stromal cells, for steroid-refractory acute GVHD in children 2 months and older.[23] The approval rested on a single-arm study of 54 children, of whom 30 percent had a complete response and 41 percent a partial response at day 28.[23] On 30 June 2026 the agency approved TREGZI, a donor product that combines blood stem and progenitor cells with regulatory T cells and other T cells (its proper name is “allogeneic regulatory T cell immunotherapy with HSPC and T cells”). It is used in matched donor transplants after myeloablative conditioning in adults with blood cancers, to rebuild the blood and immune systems and to improve survival free of chronic GVHD.[24] As of November 2026, the FDA list of approved cellular and gene therapy products includes nine cord blood products of blood-forming cells and the expanded cord blood product omidubicel (OMISIRGE); several gene therapies made from patients’ own blood stem cells, such as ZYNTEGLO and CASGEVY[20][21]; RYONCIL; and TREGZI.[25]
Other risks include serious infections while blood counts are low, failure of the graft to take and return of the original disease.[7][16][13] Some patients die of transplant complications rather than of their disease: in the 68-patient half-matched study, deaths not caused by relapse had reached 15 percent at 1 year.[16] EBMT advises that every transplant decision weigh the risk of the disease against the risk of the transplant and the treatments available without one.[2]
Published Clinical Citations
[1] ^ Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132(4):631-644. https://doi.org/10.1016/j.cell.2008.01.025
[2] ^ Snowden JA, Sánchez-Ortega I, Corbacioglu S, et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transplantation. 2022;57(8):1217-1239. https://doi.org/10.1038/s41409-022-01691-w
[3] ^ Sender R, Milo R. The distribution of cellular turnover in the human body. Nature Medicine. 2021;27(1):45-48. https://doi.org/10.1038/s41591-020-01182-9
[4] ^ Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. Journal of Hematotherapy. 1996;5(3):213-226. https://doi.org/10.1089/scd.1.1996.5.213
[5] ^ Passweg JR, Baldomero H, Atlija M, et al. The 2023 EBMT report on hematopoietic cell transplantation and cellular therapies. Increased use of allogeneic HCT for myeloid malignancies and of CAR-T at the expense of autologous HCT. Bone Marrow Transplantation. 2025;60(4):519-528. https://doi.org/10.1038/s41409-025-02524-2
[6] ^ Miller JP, Perry EH, Price TH, et al. Recovery and safety profiles of marrow and PBSC donors: experience of the National Marrow Donor Program. Biology of Blood and Marrow Transplantation. 2008;14(9 Suppl):29-36. https://doi.org/10.1016/j.bbmt.2008.05.018
[7] ^ Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. New England Journal of Medicine. 2012;367(16):1487-1496. https://doi.org/10.1056/NEJMoa1203517
[8] ^ Pulsipher MA, Chitphakdithai P, Miller JP, et al. Adverse events among 2408 unrelated donors of peripheral blood stem cells: results of a prospective trial from the National Marrow Donor Program. Blood. 2009;113(15):3604-3611. https://doi.org/10.1182/blood-2008-08-175323
[9] ^ US Food and Drug Administration. Cord Blood Banking: Information for Consumers. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/cord-blood-banking-information-consumers
[10] ^ Ballen K. Update on umbilical cord blood transplantation. F1000Research. 2017;6:1556. https://doi.org/10.12688/f1000research.11952.1
[11] ^ Sugimura R, Jha DK, Han A, et al. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature. 2017;545(7655):432-438. https://doi.org/10.1038/nature22370
[12] ^ Zeiser R, Blazar BR. Acute graft-versus-host disease: biologic process, prevention, and therapy. New England Journal of Medicine. 2017;377(22):2167-2179. https://doi.org/10.1056/NEJMra1609337
[13] ^ Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. New England Journal of Medicine. 2017;376(14):1311-1320. https://doi.org/10.1056/NEJMoa1611750
[14] ^ Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75(3):555-562. PMID 2297567. https://pubmed.ncbi.nlm.nih.gov/2297567/
[15] ^ Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biology of Blood and Marrow Transplantation. 2009;15(12):1628-1633. https://doi.org/10.1016/j.bbmt.2009.07.004
[16] ^ Luznik L, O’Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biology of Blood and Marrow Transplantation. 2008;14(6):641-650. https://doi.org/10.1016/j.bbmt.2008.03.005
[17] ^ Gratwohl A, Pasquini MC, Aljurf M, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematology. 2015;2(3):e91-e100. https://doi.org/10.1016/S2352-3026(15)00028-9
[18] ^ Kanate AS, Majhail NS, Savani BN, et al. Indications for hematopoietic cell transplantation and immune effector cell therapy: guidelines from the American Society for Transplantation and Cellular Therapy. Biology of Blood and Marrow Transplantation. 2020;26(7):1247-1256. https://doi.org/10.1016/j.bbmt.2020.03.002
[19] ^ Angelucci E, Matthes-Martin S, Baronciani D, et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014;99(5):811-820. https://doi.org/10.3324/haematol.2013.099747
[20] ^ US Food and Drug Administration. ZYNTEGLO (betibeglogene autotemcel). https://www.fda.gov/vaccines-blood-biologics/zynteglo
[21] ^ US Food and Drug Administration. CASGEVY (exagamglogene autotemcel). Content current as of 2 July 2026. https://www.fda.gov/vaccines-blood-biologics/casgevy
[22] ^ Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. New England Journal of Medicine. 2020;382(19):1800-1810. https://doi.org/10.1056/NEJMoa1917635
[23] ^ US Food and Drug Administration. FDA approves first mesenchymal stromal cell therapy to treat steroid-refractory acute graft-versus-host disease. News release, 18 December 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host
[24] ^ US Food and Drug Administration. TREGZI (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq). Content current as of 31 July 2026. https://www.fda.gov/vaccines-blood-biologics/tregzi
[25] ^ US Food and Drug Administration. Approved Cellular and Gene Therapy Products. Content current as of 30 October 2026. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products