MSC for ex vivo expansion of umbilical cord blood cells

Ex vivo expansion of umbilical cord blood (UCB) has been proposed to increase the cell dose to enhance engraftment of UCB products used as a source of hematopoietic stem cell (HSC) transplant for hematological malignancies in adults. UCB offers several potential advantages over bone marrow from unrelated donors, including its ready availability, allowance of higher HLA disparity, and lower incidence of graft-versus-host disease which makes it an attractive source especially for minority populations. The major limitation to a wider use of this source of HSC is the relatively low number of progenitor cells in the graft. For this reason, adult UCB transplantation is usually associated with delayed engraftment and increased rates of infectious complications. UCB ex vivo expansion holds the promise of delivering higher cell doses and improved outcomes. Current approaches for expansion of UCB products involve initial isolation of hematopoietic stem and progenitor cells based upon expression of CD34 or CD133 prior to culture; however, this process results in variable recovery of CD34⁺ cells and variable purity resulting in poor expansion. We have developed methods for the expansion of UCB products which eliminate the requirement for positive selection and enable the expansion of mononuclear cells by coculture on mesenchymal stromal cells. Here we discuss different methods of expansion, their shortcomings, and future directions.