Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties

Thomas J. Bartosh, Joni H. Ylöstalo, Arezoo Mohammadipoor, Nikolay Bazhanov, Katie Coble, Kent Claypool, Ryang Hwa Lee, Hosoon Choi, Darwin J. Prockop

Research output: Contribution to journalArticlepeer-review

489 Scopus citations

Abstract

Previous reports suggested that culture as 3D aggregates or as spheroids can increase the therapeutic potential of the adult stem/progenitor cells referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). Here we used a hanging drop protocol to prepare human MSCs (hMSCs) as spheroids that maximally expressed TNFα stimulated gene/protein 6 (TSG-6), the antiinflammatory protein that was expressed at high levels by hMSCs trapped in the lung after i.v. infusion and that largely explained the beneficial effects of hMSCs in mice with myocardial infarcts. The properties of spheroid hMSCs were found to depend critically on the culture conditions. Under optimal conditions for expression of TSG-6, the hMSCs also expressed high levels of stanniocalcin-1, a protein with both antiinflammatory and antiapoptotic properties. In addition, they expressed high levels of three anticancer proteins: IL-24, TNFα-related apoptosis inducing ligand, and CD82. The spheroid hMSCs were more effective than hMSCs from adherent monolayer cultures in suppressing inflammatory responses in a coculture system with LPS-activated macrophages and in a mouse model for peritonitis. In addition, the spheroid hMSCs were about one-fourth the volume of hMSCs from adherent cultures. Apparently as a result, larger numbers of the cells trafficked through the lung after i.v. infusion and were recovered in spleen, liver, kidney, and heart. The data suggest that spheroid hMSCs may be more effective than hMSCs from adherent cultures in therapies for diseases characterized by sterile tissue injury and unresolved inflammation and for some cancers that are sensitive to antiinflammatory agents.

Original languageEnglish (US)
Pages (from-to)13724-13729
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number31
DOIs
StatePublished - Aug 3 2010

Keywords

  • Inflammation
  • MSC
  • Spheroid
  • Stanniocalcin-1
  • TNFα stimulated gene/protein 6

ASJC Scopus subject areas

  • General

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