PMID- 23978474 OWN - NLM STAT- MEDLINE DCOM- 20140607 LR - 20171116 IS - 1876-7753 (Electronic) IS - 1873-5061 (Linking) VI - 11 IP - 3 DP - 2013 Nov TI - Endothelial cells provide a niche for placental hematopoietic stem/progenitor cell expansion through broad transcriptomic modification. PG - 1074-90 LID - S1873-5061(13)00110-4 [pii] LID - 10.1016/j.scr.2013.07.010 [doi] AB - Umbilical cord blood (UCB) is an attractive source of hematopoietic stem cells (HSCs). However, the number of HSCs in UCB is limited, and attempts to amplify them in vitro remain inefficient. Several publications have documented amplification of hematopoietic stem/progenitor cells (HSPCs) on endothelial or mesenchymal cells, but the lack of homogeneity in culture conditions and HSC definition impairs direct comparison of these results. We investigated the ability of different feeder layers, mesenchymal progenitors (MPs) and endothelial cells (ECs), to amplify hematopoietic stem/progenitor cells. Placental derived HSPCs (defined as Lin(-)CD45(-/dim)CD34(+)CD38(-)CD90(+)) were maintained on confluent feeder layers and the number of cells and their marker expression were monitored over 21 days. Although both types of feeder layers supported hematopoietic expansion, only endothelial cells triggered amplification of Lin(-)CD45(-/dim)CD34(+)CD38(-)CD90(+) cells, which peaked at 14 days. The amplified cells differentiated into all cell lineages, as attested by in vitro colony-forming assays, and were capable of engraftment and multi-lineage differentiation in sub-lethally irradiated mice. Mesenchymal progenitors promoted amplification of CD38(+) cells, previously defined as precursors with more limited differentiation potential. A competitive assay demonstrated that hematopoietic stem/progenitor cells had a preference for interacting with endothelial cells in vitro. Cytokine and transcriptomic analysis of both feeder cell types identified differences in gene expression that correlated with propensity of ECs and MPs to support hematopoietic cell amplification and differentiation respectively. Finally, we used RNA sequencing of endothelial cells and HSPCs to uncover relevant networks illustrating the complex interaction between endothelial cells and HSPCs leading to stem/progenitor cell expansion. CI - (c) 2013. FAU - Raynaud, Christophe M AU - Raynaud CM AD - Qatar Cardiovascular Research Center, Qatar Foundation, Qatar Science and Technology Park, Doha, Qatar. FAU - Butler, Jason M AU - Butler JM FAU - Halabi, Najeeb M AU - Halabi NM FAU - Ahmad, Faizzan S AU - Ahmad FS FAU - Ahmed, Badereldeen AU - Ahmed B FAU - Rafii, Shahin AU - Rafii S FAU - Rafii, Arash AU - Rafii A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130809 PL - England TA - Stem Cell Res JT - Stem cell research JID - 101316957 RN - 0 (Antigens, CD34) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Animals MH - Antigens, CD34/metabolism MH - Cell Communication MH - Cell Differentiation MH - Cell Lineage MH - Cells, Cultured MH - Endothelial Cells/*cytology MH - Female MH - Fetal Blood/cytology MH - Hematopoietic Stem Cell Transplantation MH - Hematopoietic Stem Cells/*cytology/metabolism MH - Humans MH - Leukocyte Common Antigens/metabolism MH - Mice MH - Placenta/*cytology MH - Pregnancy MH - Signal Transduction MH - Stem Cell Niche MH - *Transcriptome EDAT- 2013/08/28 06:00 MHDA- 2014/06/08 06:00 CRDT- 2013/08/28 06:00 PHST- 2013/01/09 00:00 [received] PHST- 2013/07/17 00:00 [revised] PHST- 2013/07/31 00:00 [accepted] PHST- 2013/08/28 06:00 [entrez] PHST- 2013/08/28 06:00 [pubmed] PHST- 2014/06/08 06:00 [medline] AID - S1873-5061(13)00110-4 [pii] AID - 10.1016/j.scr.2013.07.010 [doi] PST - ppublish SO - Stem Cell Res. 2013 Nov;11(3):1074-90. doi: 10.1016/j.scr.2013.07.010. Epub 2013 Aug 9.