Abstract
Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting need for ex vivo HSPC expansion. To establish a more efficient method to expand UCB HSPCs, we developed the bioactive peptide named SL-13R and cultured UCB HSPCs (CD34+ cells) with SL-13R in animal component-free medium containing a cytokine cocktail. Following 9 days of culture with SL-13R, the numbers of total cells, CD34+, CD38− cells, and hematopoietic stem cell (HSC)-enriched cells were significantly increased relative to control. Transplantation of cells cultured with SL-13R into immunodeficient NOD/Shi-scid/IL-2Rγ knockout mice confirmed that they possess long-term reconstitution and self-renewal ability. AHNAK, ANXA2, and PLEC all interact with SL-13R. Knockdown of these genes in UCB CD34+ cells resulted in reduced numbers of hematopoietic colonies relative to SL-13R-treated and non-knockdown controls. In summary, we have identified a novel bioactive peptide SL-13R promoting expansion of UCB CD34+ cells with long-term reconstitution and self-renewal ability, suggesting its clinical use in the future.
Highlights
Introductionhematopoietic stem cell (HSC) have been applied to HSC transplantation for more than 50 years as curative treatment for hematological disorders such as anemia and leukemia [1]
Flow cytometry was used to evaluate the number of CD34+, CD38– cells and hematopoietic stem cell (HSC) (CD34+, CD38−, CD90+, CD45RA−, CD49f+) [25] on DAY9 and observed a significantly greater number of CD34+, CD38– cells and HSCs in SL-13R-treated cells compared to control (CD34+, CD38– cells: 1.5-fold higher, p = 0.0049, n = 8; HSCs: 1.5fold higher, p = 0.014, n = 6) (Figure 1C,D)
To analyze the hematopoietic potential of cells cultured with SL-13R, we performed colony forming unit (CFU) assay
Summary
HSCs have been applied to HSC transplantation for more than 50 years as curative treatment for hematological disorders such as anemia and leukemia [1]. Bone marrow (BM), peripheral blood (PB) and umbilical cord blood (UCB) serve as cell sources for HSC transplantation. In the last decades UCB has attracted increasing attention because UCB have several advantages: their collection is non-invasive and safe for the donor, permissive of HLA mismatch and lower risk of graft-versus-host disease compared to BM or PB-derived CD34+ hematopoietic stem and progenitor cells (HSPCs) [2,3]. Utilization of UCB is limited as doses of HSPCs are lower in the UCB graft, which associated with inefficient engraftment and treatment-related mortality [4,5]
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