Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators

Jack M. Milwid, Jessica S. Elman, Matthew Li, Keyue Shen, Arjun Manrai, Aaron Gabow, Joshua Yarmush, Yunxin Jiao, Anne Fletcher, Jungwoo Lee, Michael J. Cima, Martin L. Yarmush, Biju Parekkadan

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)999-1007
Number of pages9
JournalMolecular Therapy
Volume22
Issue number5
DOIs
StatePublished - May 2014

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Mesenchymal Stromal Cells
Interleukin-10
Proteins
Proteomics
Gene Expression Profiling
Stromal Cells
Septic Shock
Libraries
Anti-Inflammatory Agents
Gene Expression
Survival
Health

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Genetics
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology

Cite this

Milwid, Jack M. ; Elman, Jessica S. ; Li, Matthew ; Shen, Keyue ; Manrai, Arjun ; Gabow, Aaron ; Yarmush, Joshua ; Jiao, Yunxin ; Fletcher, Anne ; Lee, Jungwoo ; Cima, Michael J. ; Yarmush, Martin L. ; Parekkadan, Biju. / Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators. In: Molecular Therapy. 2014 ; Vol. 22, No. 5. pp. 999-1007.
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Milwid, JM, Elman, JS, Li, M, Shen, K, Manrai, A, Gabow, A, Yarmush, J, Jiao, Y, Fletcher, A, Lee, J, Cima, MJ, Yarmush, ML & Parekkadan, B 2014, 'Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators', Molecular Therapy, vol. 22, no. 5, pp. 999-1007. https://doi.org/10.1038/mt.2014.17

Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators. / Milwid, Jack M.; Elman, Jessica S.; Li, Matthew; Shen, Keyue; Manrai, Arjun; Gabow, Aaron; Yarmush, Joshua; Jiao, Yunxin; Fletcher, Anne; Lee, Jungwoo; Cima, Michael J.; Yarmush, Martin L.; Parekkadan, Biju.

In: Molecular Therapy, Vol. 22, No. 5, 05.2014, p. 999-1007.

Research output: Contribution to journalArticle

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