Mesenchymal stem cells increase T-regulatory cells and improve healing following trauma and hemorrhagic shock

Amy V. Gore, Letitia E. Bible, Kimberly Song, David H. Livingston, Alicia M. Mohr, Ziad C. Sifri

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

BACKGROUND: Rodent lungs undergo full histologic recovery within 1 week following unilateral lung contusion (LC). However, when LC is followed by hemorrhagic shock (HS), healing is impaired. We hypothesize that the intravenous administration of mesenchymal stem cells (MSCs) in animals undergoing combined LC followed by HS (LCHS) will improve wound healing. METHODS: Male Sprague-Dawley rats (n = 5-6 per group) were subjected to LCHS with or without the injection of a single intravenous dose of 5 × 106 MSCs following return of shed blood after HS. Rats were sacrificed 7 days following injury. Flow cytometry was used to determine the T-regulatory cell (Treg) population in peripheral blood. Lung histology was graded using a well-established lung injury score (LIS). Components of the LIS include average inflammatory cells per high-power field over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with total scores ranging from 0 to 11. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). p < 0.05 was considered significant. RESULTS: Seven days following isolated LC, animals demonstrated lung healing with an LIS unchanged from naive. The addition of HS resulted in a persistently elevated LIS score, whereas the addition of MSCs to LCHS decreased the LIS score back to naive levels. The change in LIS was driven by a significant decrease in edema scores. In rats undergoing LC alone, 10.5% (3.3%) of CD4+ cells were Tregs. The addition of HS caused no significant change in Treg population (9.3% [0.7%]), whereas LCHS + MSC significantly increased the population to 18.2% (6.8%) in peripheral blood (p < 0.05 vs. LCHS). CONCLUSION: Impaired wound healing following trauma and HS is improved by a single dose of MSCs given immediately after injury. This enhanced healing is associated with an increase in the Treg population and a significant decrease in lung edema score as compared with animals undergoing LCHS. Further study into the role of Tregs in MSC-mediated wound healing is warranted.

Original languageEnglish (US)
Pages (from-to)48-52
Number of pages5
JournalJournal of Trauma and Acute Care Surgery
Volume79
Issue number1
DOIs
StatePublished - Jul 3 2015

All Science Journal Classification (ASJC) codes

  • Surgery
  • Critical Care and Intensive Care Medicine

Keywords

  • Cell-based therapy
  • MSCs
  • immunomodulation
  • lung Injury
  • rats

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