Indications for Utilization of Stored Umbilical Cord Blood

By Mitchell S. Cairo, MD, and Tamila L. Kindwall-Keller, DO, MS
Updated:  September 2019


Since the first umbilical cord blood transplantation in 1988 for Fanconi’s anemia (1), umbilical cord blood has become a safe and dependable alternative donor graft source for use in allogeneic hematopoietic cell transplantation. Approximately 10% of alternative donor grafts for adult hematopoietic cell transplants are umbilical cord blood.(2)

Umbilical cord blood has many advantages including rapid availability, less graft-versus-host disease, low CMV transmission, and tolerance to human leukocyte antigen (HLA) disparities. Umbilical cord blood cells can restore hematopoiesis after conditioning regimens for malignant as well as non-malignant disorders. Moreover, umbilical cord blood contains non-hematopoietic stem and progenitor cells that are capable of differentiating into a variety of different cell types and tissue lineages.(3) This plasticity allows umbilical cord blood to be used for novel regenerative medicine research for a wide variety of indications such as neurodegenerative diseases, cerebral palsy, diabetes and its complications, and congenital heart conditions. With increased usage of umbilical cord blood for allogeneic hematopoietic cell transplantation and regenerative medicine, both public and private cord blood banks provide options for the storage of umbilical cord blood for use in the general population (public banks) or for family-directed donation (private banks).


The most common use of umbilical cord blood is as a graft source after conditioning chemotherapy for allogeneic hematopoietic cell transplant restoring hematopoiesis (Table 1). A majority of umbilical cord blood used for the hematopoietic cell transplant indication is donated anonymously through a public bank or, less often, privately through a directed family donation. Even though the HLA matching is less stringent with umbilical cord blood than adult matched unrelated donors, the risk of graft-versus-host disease is less. However, the risk of engraftment failure due to low cell dose is greater using umbilical cord blood. Ongoing research is evaluating ways to improve engraftment in patients receiving umbilical cord blood transplant such as ex-vivo expansion strategies, accessory cell populations, improved cord blood homing, and ex-vivo expression/engineering of cord blood immune cells (Table 2).

Regenerative Medicine

Umbilical cord blood-based therapies are now being used increasingly for novel applications in non-hematopoietic diseases as a form of cellular regenerative therapy or immune modulation (Table 3). These indications use autologous banking and are still considered investigational and should only be performed on a clinical trial. Families who are interested in participating in a clinical trial should visit

Role of Private Cord Blood Banks

Most of the umbilical cord blood units used for hematopoietic cell transplantation in children and adults are obtained through public umbilical cord blood banks. Rarely do recipients of umbilical cord blood transplants have family members who have donated umbilical cord blood to a private bank. In a review performed by the Center for International Blood and Marrow Transplant Research (CIBMTR), a total of 244 patients received directed-family umbilical cord blood transplants from 73 centers in a 12-year time frame from 2000 to 2012.(9) These transplants were performed most commonly for acute leukemia (37%), hemoglobinopathies (29%), Fanconi’s anemia (7%), and immune or metabolic disorders (18%). More than 500 patients transplanted with related umbilical cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with nonmalignant diseases and 56% for patients with malignant diseases.(10) Main hematologic indications for treatment in children were leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders (Table 4).


Umbilical cord blood can reconstitute hematopoiesis after conditioning chemotherapy for malignant and non-malignant disorders. The availability of umbilical cord blood through public and private banks allows patients who would not otherwise have a graft source proceed to a potentially life-saving hematopoietic cell transplant. Since umbilical cord blood can regenerate tissue and modulate the immune system, umbilical cord blood has the potential to be used in the treatment of many other non-hematologic conditions.


Table 1 (4)

Diseases Treated by Umbilical Cord Blood Transplantation Using

Either Sibling or Unrelated Donors


Malignant Diseases

Non-Malignant Diseases

Acute Lymphoblastic Leukemia (ALL)

Acute Myeloblastic Leukemia (AML)

Juvenile Chronic Myelogenous Leukemia (JMML)

Chronic Lymphocytic Leukemia (CLL)

Chronic Myelogenous Leukemia (CML)

Non-Hodgkin Lymphoma (NHL)

Hodgkin Lymphoma (HL)


Myelodysplastic Syndrome


Multiple myeloma

Solid Tumors

Fanconi Anemia

Idiopathic Aplastic Anemia


Sickle Cell Anemia

Amegakaryocytic Thrombocytopenia

Kostman Syndrome

Blackfan-Diamond Syndrome

Dyskeratosis Congenita

Severe Combined Immunodeficiency

X-linked Lymphoproliferative Syndrome

Wiskott-Aldrich Syndrome

Krabbe’s Disease

Hurler Syndrome

Sanfilippo Syndrome

Hunter Syndrome

Gunther Disease


Globoid Cell Leukodystrophy

Metachomatic Leukodystrophy


Tay-Sachs Disease

Lesch-Nyhan Syndrome

Sandhoff Disease

Other rare metabolic and primary               immunodeficiency diseases

Modified from Cairo et al, BBMT, 2008


Table 2 (5, 6)

Experimental Approaches of Cord Blood Transplantation

  • Ex-Vivo Expansion Strategies
    • Notch Ligand Delta 1
    • Stem-Regenin I (SRI)
    • Nicotinamide
    • Copper Chelation (TEPA)
    • Accessory Cell Populations
      • Double Umbilical Cord Blood Transplantation
      • Haploidentical Peripheral Blood Stem Cells
      • Ex-Vivo Expanded Mesenchymal Stromal Cells (MSC) Co-culture
      • Human Placental Derived Stem Cells (HPDSCs)
      • Improved Cord Blood Homing
        • Prostaglandin E2 (PG-E2)
        • Inhibition of CD26 Peptidase (Sitagliptin)
        • Ex-vivo Fucosylation of HSC/HPC
        • Intraosseous CB Infusion
        • Ex-Vivo Expression/Engineering of CB Immune Cells
          • Multiviral Cord Blood Cytotoxic T-Lymphocytes (CTLs)
          • CB NK Cells
          • CB T-Regulatory Cells (T-regs)

Modified Cairo et al, BMT, 2016 and Danby and Rocha et al, Frontiers in Immunology, 2014.


Table 3 (5, 7, 8)

Novel Uses of Umbilical Cord Blood Use in Regenerative Medicine


Diseases Being Studied

Spinal Cord Injury

Type I  and Type II Diabetes Mellitus

Infant Lung Disease

Congenital Diaphragmatic Hernia

Acute Ischemic Stroke

Thromboangiitis Obliterans

Neurodegenerative Disorders

Critical Limb Ischemia

Cerebral Palsy

Traumatic Brain Injury

Autism Spectrum Disorder

Congenital Heart Disease

Preterm Neonatal Complications

Hypoplastic Left Heart Syndrome

Global Developmental Delay

Idiopathic Dilated Cardiomyopathy


Liver Cirrhosis

Epidermolysis Bullosa

Viral Hepatitis

Rheumatoid Arthritis

Ulcerative Colitis / Inflammatory Bowel Disease

Systemic Lupus Erythematosus

Duchenne Muscular Dystrophy

Childhood Hearing Loss


Hypoxic-Ischemic Encephalopathy

In-Utero Brain Injury / Stroke

Sweat Gland Diseases

Amyotropic Lateral Sclerosis

Parkinson’s Disease


Corneal Epithelial Wounds

Diabetic Foot Ulcers


Table 4 (10)

Related Umbilical Cord Blood Transplants Reported to EUROCORD


Malignant Diseases

Non-Malignant Diseases

Acute Lymphoblastic Leukemia

Metabolic Diseases

Acute Myelogenous Leukemia

Fanconi Anemia

Myelodysplastic Syndrome


Chronic Myelogenous Leukemia

Sickle Cell Disease

Non-Hodgkin’s Lymphoma

Subacute Combined Immunodeficiency

Hodgkin’s Lymphoma


Solid Tumors




  1. Gluckman E, Broxmeyer HE, Auerbach AD, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989; 321: 1174-1178.
  2. D’Souza A, Fretham C. Current uses and outcomes of hematopoietic stem cell transplantation: CIBMTR Summary Slides, 2017. Available at:
  3. Iafolla MAJ, Tay J, Allan DS. Transplantation of umbilical cord blood-derived cells for novel indications in regenerative therapy or immune modulations: A scoping review of clinical studies. Biol Blood Marrow Transplant. 2014; 20: 20-25.
  4. Cairo MS, Rocha V, Gluckman E, et al. Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors. Biol Blood Marrow Transplant. 2008; 14: 44-53.
  5. Cairo MS, Tarek N, Lee DA, et al. Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients. Bone Marrow Transplant. 2016; 51: 27-33.
  6. Danby R, Rocha V. Improving engraftment and immune reconstitution in umbilical cord blood transplantation. Frontiers Immunol. 2014; 5: 68.
  7. Mazonson P, Kane M, Colberg K, et al. Prevalence of medical conditions potentially amenable to cellular therapy among families privately storing umbilical cord blood. Matern Child Health J. 2016 (online).
  9. Armson BA, Allan DS, and Casper RF. SOGC Clinical Practice Guideline. Umbilical Cord Blood: Counselling, Collection, and Banking. J Obstet Gynaecol Can. September 2015; 832-844.
  10. Gluckman E, Ruggeri A, Rocha V, et al. for Eurocord, Netcord, World Marrow Donor Association and National Marrow Donor Program. Family-directed umbilical cord blood banking. Haematologica. 2011; 96: 1700-1707.