Gupta Rajeev, Turati Virginia, Brian Duncan, Thrussel Craig, Wilbourn Barry, May Gillian, Enver Tariq
Stem Cell Group, UCL Cancer Institute, University College London, London WC1E 6BT, UK; Manual Blood Sciences, Health Services Laboratories, The Halo Building, 1 Mabledon Place, London WC1H 9AX, UK.
Stem Cell Group, UCL Cancer Institute, University College London, London WC1E 6BT, UK.
Cell Stem Cell. 2020 Apr 2;26(4):527-541.e8. doi: 10.1016/j.stem.2020.02.012. Epub 2020 Mar 19.
Umbilical cord blood (UCB) has had considerable impact in pediatric stem cell transplantation, but its wider use is limited in part by unit size. Long-term ex vivo culture offers one approach to increase engraftment capacity by seeking to expand stem and progenitor cells. Here, we show brief incubation (8 h) of UCB CD34+ cells with the matricellular regulator Nov (CCN3) increases the frequency of serially transplantable hematopoietic stem cells (HSCs) 6-fold. This rapid response suggests recruitment rather than expansion of stem cells; accordingly, in single-cell assays, Nov increases the clonogenicity of phenotypic HSCs without increasing their number through cell division. Recruitment is associated with both metabolic and transcriptional changes, and tracing of cell divisions demonstrates that the increased clonogenic activity resides within the undivided fraction of cells. Harnessing latent stem cell potential through recruitment-based approaches will inform understanding of stem cell state transitions with implications for translation to the clinic.
脐带血（UCB）在儿科干细胞移植中产生了重大影响，但其更广泛的应用在一定程度上受到单位体积的限制。长期体外培养提供了一种通过扩增干细胞和祖细胞来提高植入能力的方法。在此，我们发现将脐带血CD34+细胞与基质细胞调节因子Nov（CCN3）进行短暂孵育（8小时）可使连续可移植造血干细胞（HSC）的频率增加6倍。这种快速反应表明是干细胞的募集而非扩增；因此，在单细胞试验中，Nov增加了表型HSC的克隆形成能力，但并未通过细胞分裂增加其数量。募集与代谢和转录变化均相关，细胞分裂追踪表明增加的克隆形成活性存在于未分裂的细胞部分中。通过基于募集的方法利用潜在的干细胞潜能将有助于理解干细胞状态转变，对临床转化具有重要意义。
