The first successful human allogeneic hematopoietic stem cell transplantations (HSCT) were performed in children with congenital immunodeficiencies in 1968 (1-3). Since then, bone marrow transplantation (BMT) has been proven to cure or provide survival advantage for several malignant and nonmalignant diseases. However, several challenges limit the success rate and ability to utilize BMT. Only about 30% of potential HSCT recipients have a suitably human leukocyte antigen (HLA)–matched related donor. Unrelated donor (URD) transplants are associated with higher transplant-related mortality (TRM) due to graft failure, opportunistic infections, and graft-versus-host disease (GVHD). URD searches are time consuming with median search times reported in the range of four months (4-8). Donor attrition is another challenge: about 30% of suitably matched URD, even when identified, are not available when needed for a variety of reasons (8). As a result, only about 50% of the initiated URD searches are successful in terms of identifying an HLA-matched donor who is still motivated and available (8). Hence, an unknown number of patients succumb to their primary disease while awaiting a suitable graft (9). These limitations led to incentives for newer strategies, including the search for alternative sources of hematopoietic stem cells (HSC).
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