Enriched Protein Screening of Human Bone Marrow Mesenchymal Stromal Cell Secretions Reveals MFAP5 and PENK as Novel IL-10 Modulators
| Autor: | Keyue Shen, Michael J. Cima, Jungwoo Lee, Arjun K. Manrai, Biju Parekkadan, Martin L. Yarmush, Aaron Gabow, Joshua Yarmush, Yunxin Jiao, Jack M. Milwid, Jessica S Elman, Anne L. Fletcher, Matthew D. Li |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Koch Institute for Integrative Cancer Research at MIT, Milwid, Jack Miles, Li, Matthew, Manrai, Arjun Kumar, Cima, Michael J |
| Rok vydání: | 2014 |
| Předmět: |
Proteomics
Stromal cell Cell Bone Marrow Cells Biology Mice 03 medical and health sciences Contractile Proteins 0302 clinical medicine Gene expression Drug Discovery medicine Genetics Animals Humans Protein Precursors Molecular Biology Glycoproteins 030304 developmental biology chemistry.chemical_classification Pharmacology Extracellular Matrix Proteins 0303 health sciences Gene Expression Profiling Mesenchymal stem cell Proteins Mesenchymal Stem Cells Enkephalins Shock Septic Molecular biology Interleukin-10 3. Good health Cell biology Gene expression profiling medicine.anatomical_structure Secretory protein chemistry Protein Biosynthesis 030220 oncology & carcinogenesis Intercellular Signaling Peptides and Proteins Molecular Medicine Original Article RNA Splicing Factors Glycoprotein |
| Zdroj: | Elsevier |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2014.17 |
| Popis: | 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. © 2014 The American Society of Gene and Cell Therapy. National Human Genome Research Institute (U.S.) (Grant T32 HG002295) |
| Databáze: | OpenAIRE |
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