1. Increasing cord blood cell dose
· Improved CB collection, processing, freezing, and thawing.
· Consecutive infusion of two CBUs (RS; Prospective phase II/III clinical trials; Clinical use).
· Ex vivoexpansion of CB (Phase I/II/III clinical trials).
· Infusion of CBU with third-party donor cells (Phase II clinical trials).
2. Improved delivery and homing HSC to bone marrow niche
· Direct intra-bone infusion of CB (Phase I/II clinical trials).
· Inhibition of CD26 peptidase (Phase II clinical trials).
· Ex vivo Fucosylation of CB HSC/HPC (Phase I/II clinical trials).
3. Improved selection of CBU
·Enhanced HLA-matching (RS; PSO).
·Detection of donor specific HLA-antibodies (RS; PSO).
·Use of KIR matching (RS).
4. Modification of transplant protocol
· Using reduced intensity conditioning (RS; Prospective phase II/III clinical trials; Clinical use).
· Modification of graft-versus-host disease prophylaxis (RS; PSO).
5. Post-transplant use of growth factors/cytokines
· Administration of granulocyte colony stimulating factor (GCSF) (Regular clinical use).
· Administration of stem cell factor (SCF) (Pre-clinical studies).
· Administration of Eltrombopag (Phase II clinical trials).
6. Infusion of CB with accessory cells
· Use of Mesenchymal stem cells (Phase I/II clinical trials).
· Use of regulatory T cells (Phase I/II clinical trials).
Table 1: Current strategies to improve engraftment following umbilical cord blood transplantation. (CB: Cord Blood; CBU: Cord Blood Unit; HSC: Hematopoietic Stem Cells; HPC: Hematopoietic Progenitor Cells; HLA: Human Leukocyte Antigen; KIR: killer Immunoglobulin-like Receptor; RS: Retrospective Studies; PSO: Prospective Observational Studies).