PLoS ONE (Jan 2017)

Mesenchymal stromal cells (MSCs) induce ex vivo proliferation and erythroid commitment of cord blood haematopoietic stem cells (CB-CD34+ cells).

  • Simone Perucca,
  • Andrea Di Palma,
  • Pier Paolo Piccaluga,
  • Claudia Gemelli,
  • Elisa Zoratti,
  • Giulio Bassi,
  • Edoardo Giacopuzzi,
  • Andrea Lojacono,
  • Giuseppe Borsani,
  • Enrico Tagliafico,
  • Maria Teresa Scupoli,
  • Simona Bernardi,
  • Camilla Zanaglio,
  • Federica Cattina,
  • Valeria Cancelli,
  • Michele Malagola,
  • Mauro Krampera,
  • Mirella Marini,
  • Camillo Almici,
  • Sergio Ferrari,
  • Domenico Russo

DOI
https://doi.org/10.1371/journal.pone.0172430
Journal volume & issue
Vol. 12, no. 2
p. e0172430

Abstract

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A human bone marrow-derived mesenchymal stromal cell (MSCs) and cord blood-derived CD34+ stem cell co-culture system was set up in order to evaluate the proliferative and differentiative effects induced by MSCs on CD34+ stem cells, and the reciprocal influences on gene expression profiles. After 10 days of co-culture, non-adherent (SN-fraction) and adherent (AD-fraction) CD34+ stem cells were collected and analysed separately. In the presence of MSCs, a significant increase in CD34+ cell number was observed (fold increase = 14.68), mostly in the SN-fraction (fold increase = 13.20). This was combined with a significant increase in CD34+ cell differentiation towards the BFU-E colonies and with a decrease in the CFU-GM. These observations were confirmed by microarray analysis. Through gene set enrichment analysis (GSEA), we noted a significant enrichment in genes involved in heme metabolism (e.g. LAMP2, CLCN3, BMP2K), mitotic spindle formation and proliferation (e.g. PALLD, SOS1, CCNA1) and TGF-beta signalling (e.g. ID1) and a down-modulation of genes participating in myeloid and lymphoid differentiation (e.g. PCGF2) in the co-cultured CD34+ stem cells. On the other hand, a significant enrichment in genes involved in oxygen-level response (e.g. TNFAIP3, SLC2A3, KLF6) and angiogenesis (e.g. VEGFA, IGF1, ID1) was found in the co-cultured MSCs. Taken together, our results suggest that MSCs can exert a priming effect on CD34+ stem cells, regulating their proliferation and erythroid differentiation. In turn, CD34+ stem cells seem to be able to polarise the BM-niche towards the vascular compartment by modulating molecular pathways related to hypoxia and angiogenesis.