@article{4dec977a916f46b08516f6668aab7cc4,
title = "Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators",
abstract = "The secreted proteins from a cell constitute a natural biologic library that can offer significant insight into human health and disease. Discovering new secreted proteins from cells is bounded by the limitations of traditional separation and detection tools to physically fractionate and analyze samples. Here, we present a new method to systematically identify bioactive cell-secreted proteins that circumvent traditional proteomic methods by first enriching for protein candidates by differential gene expression profiling. The bone marrow stromal cell secretome was analyzed using enriched gene expression datasets in combination with potency assay testing. Four proteins expressed by stromal cells with previously unknown anti-inflammatory properties were identified, two of which provided a significant survival benefit to mice challenged with lethal endotoxic shock. Greater than 85% of secreted factors were recaptured that were otherwise undetected by proteomic methods, and remarkable hit rates of 18% in vitro and 9% in vivo were achieved.",
author = "Milwid, {Jack M.} and Elman, {Jessica S.} and Matthew Li and Keyue Shen and Arjun Manrai and Aaron Gabow and Joshua Yarmush and Yunxin Jiao and Anne Fletcher and Jungwoo Lee and Cima, {Michael J.} and Yarmush, {Martin L.} and Biju Parekkadan",
note = "Funding Information: We would like to acknowledge John Asara for assistance with the mass spectrometry, Mick Correll for assistance with the gene expression analysis, and Patricia Della Pelle and Ryan Murray for assistance with histology and image acquisition. We would also like to acknowledge David Yarmush and Michael Cima for helpful discussions and insight. The research was funded in part by grants from the National Institutes of Health: K01DK087770 (B.P.), R01EB012521 (B.P.), R01DK43371 (M.L.Y.), the Shriners Hospitals for Children (B.P.). J.M.M. was partially supported by a training grant from the National Human Genome Research Institute (T32 HG002295). J.M.M. conceived the ideas, designed and executed the experiments, interpreted data, and wrote the manuscript. M.L. designed and executed the experiments. A.G. analyzed the gene expression data. M.F. performed the western blots. Y.J. assisted in the recombinant protein screen. J.L. assisted in the animal experiments. M.L.Y. interpreted data and provided funding. B.P. conceived the ideas, designed and executed the experiments, interpreted data, wrote the manuscript, and provided funding. J.M.M., M.L., M.L.Y., and B.P. are listed as inventors on a patent application that pertains to the presented results.",
year = "2014",
month = may,
doi = "10.1038/mt.2014.17",
language = "English (US)",
volume = "22",
pages = "999--1007",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "5",
}