Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease [transcriptome dataset]. Small sized mesenchymal stem-cells primed with hypoxia attenuate graft-versus-host disease [transcriptome dataset]

Mesenchymal stem-cells (MSCs) are of particular interest for treating immune-related diseases due to their immunosuppressive capacities. Here, we show that Small sized MSCs primed with Hypoxia and Calcium ion (SHC-MSCs) exhibit the enhanced functions regarding stemness and immunomodulation for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord-blood MSCs, SHC-MSCs were resistant to the passage dependent cellular senescence mediated by MCP-1 and p53/p21 cascade and highly secreted the pro-angiogenic and immune-modulatory factors, resulting in suppression of T-cell proliferation. Genome-wide DNA methylome and transcriptome analysis indicate that SHC-MSCs characteristically up-regulated immune-modulation, cell adhesion and cell-cycle related genes. As downstream factors, PLK1, ZNF143, DHRS3, and FOG2 proteins played a key role on the beneficial effects of SHC-MSCs, evidenced by the promoted self-renewal, migration, pro-angiogenic, anti-inflammatory, and T cell suppression capacities in their-over-expressing MSCs. Importantly, administration of SHC-MSCs or PLK1-over-expressing cells (PLK1-MSCs) significantly reduced the symptoms of graft-versus-host disease (GVHD) in a humanized mouse model which led to significantly improved survival, less weight loss, and less histopathologic injuries of GVHD target organs compared with naive MSC-infused mice. Collectively, our study suggests that small-sized MSCs primed with hypoxia could advance the therapeutic strategy for the clinical treatment of allogeneic conflicts including GVHD. Overall design: Human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) were normally maintained (NT) or cultivated by SHC procedure (SHC) which enriched small sized cells and at the same time primed with hypoxia ( 3 % oxygen) and calcium ion (1.8 mM). Total RNA from three independent replicates was isolated using the RNeasy Mini Kit (QIAGEN, Valencia, CA), including treatment with DNase I (QIAGEN). One ug of total RNA was used for the Affymetrix GeneChip Human 2.0 ST Array (Affymetrix, Santa Clara, CA), in accordance with the manufacturer’s instructions.