Incubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan.
Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan.
Molecules. 2021 Apr 1;26(7):1995. doi: 10.3390/molecules26071995.
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.
造血干细胞和祖细胞（HSPC）移植是一种治疗血液系统疾病的有疗效的方法，已经应用了几十年。虽然脐带血（UCB）是 HSPC 的有前途的来源，但这些制剂中 HSPC 的剂量较低限制了其使用，促使需要进行 HSPC 的体外扩增。为了建立一种更有效的扩增 UCB HSPC 的方法，我们开发了一种名为 SL-13R 的生物活性肽，并在不含动物成分的培养基中，用包含细胞因子鸡尾酒的 SL-13R 培养 UCB HSPC（CD34+细胞）。用 SL-13R 培养 9 天后，与对照相比，总细胞数、CD34+、CD38-细胞和造血干细胞（HSC）富集细胞的数量显著增加。将用 SL-13R 培养的细胞移植到免疫缺陷的 NOD/Shi-scid/IL-2Rγ 敲除小鼠中证实，它们具有长期重建和自我更新的能力。AHNAK、ANXA2 和 PLEC 都与 SL-13R 相互作用。在 UCB CD34+细胞中敲低这些基因，与 SL-13R 处理组和非敲低对照组相比，造血集落的数量减少。总之，我们已经鉴定出一种促进 UCB CD34+细胞扩增的新型生物活性肽 SL-13R，具有长期重建和自我更新的能力，提示其未来在临床上的应用。
