Initially used as an alternative hematopoietic stem cell source for patients without a
human leukocyte antigen-matched bone marrow or peripheral blood stem cell donor, unrelated cord blood (UCB) is now the preferred donor source when
hematopoietic stem cell transplantation (HSCT) is used to treat patients with lysosomal storage disorders (
LSD). Without
transplantation, these patients have serious progressive multi-system deterioration and premature death. UCB
transplantation favorably alters the natural history of these diseases and prolongs survival. It primarily works through cellular
enzyme replacement by healthy engrafted donor cells providing a continuous endogenous supply of
enzyme throughout the body and, thorough engraftment of donor-derived microgial cells, in the central nervous system. HSCT in
LSD, the majority performed in patients with
mucopolysaccharidoses and leukodystrophies, is associated with remarkably high rates of engraftment and survival. Importantly, recipients of UCB, as compared with other donor sources, more often achieve full-donor chimerism and normalization of
enzyme levels, which has been associated with superior long-term clinical prognosis. Additionally, UCB units are readily available, reducing time to
transplantation and thereby providing access to transplant at young ages, another highly important predictor for long-term neuro-developmental function. For these reasons, UCB grafts are nowadays considered to be the optimal graft source for HSCT in patients with
LSD.