**3. Other uses of UCB**

**•** Sanfilippo disease (mucopolysaccharidosis type III) **•** Morquio syndrome (mucopolysaccharidosis type IV) **•** Maroteaux-Lamy disease (mucopolysaccharidosis type VI)

142 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

**•** Krabbe disease (galactosylceramide lipidosis) **•** Inclusion-cell disease (mucolipidosis II) **•** Wolman disease (acid lipase deficiency)

**•** Sandhoff disease (hexosaminidase A and B deficiency) **•** Tay-Sachs disease (hexosaminidase A deficiency)

**•** Neimann-Pick Disease (sphingomyelin lipidosis, sphingomyelinase deficiency)

**•** Lesch-Nyhan syndrome (hypoxanthine guanine phosphoribosyl transferase/HPRT deficiency)

**Table 2.** Disease indications that may be treated with allogeneic cord blood transplantation based on information in [3,

Graft failure and delayed immune reconstitution in UCB HSCT with myeloablative therapy are not without risk, and only 25% of the patients have a matched sibling donor. Lower UCB HSC engraftment rates have been observed where resistance to engraftment occurs (e.g., hemoglobinopathies, chronic myeloid leukemia, and acquired aplastic anemia, see Ref. [4]). Autologous UCB HSCTs have been less common than allogeneic transplants, but the recent development of novel genome editing technologies opens the way to using this new technology to correct certain inherited or acquired gene disorders in autologous HSCs and sourced from UCB at birth or alternatively from mobilized peripheral blood and bone marrow as appropriate, and to then transplant these cells into the affected individual to correct the disease. HLA matching of these grafts and hence GvHD has not, to date, been a problem for these autologous transplants. However, the use of myeloablative conditioning creates a substantial risk. Recently, studies in mice suggest that the risk of myeloablative conditioning can be greatly reduced by using CD45-saporin toxin conjugated antibody treatment to make space in the bone marrow for transplanted cells to treat sickle cell disease in the autologous setting without significant adverse effects on graft recovery [39], but this has not been conducted in the human. However, earlier studies using rat CD45 antibodies produced in Cambridge, UK [40, 41] have demonstrated the safety and efficacy of an 111In-labeled CD45 conjugate in bone marrow transplant patients with acute leukemia [42]. This may then provide a safer approach with gene-modified HSCTs for treating the β-globin-associated severe hemoglobinopathies, as well as congenital immunodeficiencies and HIV AIDS. While α-thalassemia affects the production of the α-globin chain in β-thalassemia and sickle cell disease, mutations in the β-globin gene result in absent or reduced β-globin and abnormal hemoglobin structure, respectively [43– 45]. Importantly, the inherited hemoglobin disorders, the thalassemias, and sickle cell disease constitute the most common monogenic disorders worldwide [43–47]. Around 300,000

**•** Fucosidosis **•** Myelokathexis

5, 7, 29].

**•** Phosphorylase deficiency **•** X-linked adrenoleukodystrophy **•** Metachromatic leukodystrophy

> UCB hematopoietic stem and progenitor cells (HSPCs) may also be used to generate red blood cells, granulocytes, or platelets ex vivo for transfusion [11, 60]. Alternatively, and although

initial studies have used fibroblasts [61–63], UCB may be reprogrammed to induced pluripotent stem (iPS) cells [64], which can then be differentiated into different cell lineages, e.g., to generate red blood cells and platelets. As these end cells lack nuclei, they may allay certain safety concerns with respect to iPS cells and tumorigenicity (provided that enucleated cells can survive transplantation). Currently, however, these strategies do not replicate the production of over 3 × 1011 blood cells that are generated in adults per day. Other cell types may be isolated, used, expanded, or manipulated from UCB or the umbilical cord (UC) to enhance engraftment, to eradicate malignancies, to prevent GvHD, or prevent infections. The strategies to improve UCB engraftment and immune reconstitution are listed in **Table 3**. This is updated from data presented in [65].
