title: Mesenchymal stem cells enhance lung recovery after injury, shock, and chronic stress.
abstract: BACKGROUND
  Normal lung healing is impaired when lung contusion (LC) is followed by hemorrhagic shock (HS), and chronic stress (CS). Mesenchymal stem cells (MSCs) are immunomodulatory, pluripotent cells that are under investigation for use in wound healing and tissue regeneration. We hypothesized that treatment with MSCs can reverse the impaired healing seen after LC combined with HS and CS (LCHS/CS).
  
  
  METHODS
  Male Sprague-Dawley rats (n = 6/group) underwent LCHS with or without a single intravenous dose of 5 × 10(6) Sprague-Dawley rat MSCs after resuscitation. Thereafter, rats were subjected to 2 hours of CS daily on days 1-6 and were humanely killed on day 7. Lung histology was scored according to a well-established lung injury score (LIS) that included interstitial and pulmonary edema, alveolar integrity, and inflammatory cells. Scoring ranges from 0 (normal lung) to 11 (most severely injured). Whole blood was analyzed for the presence of CD4(+)CD25(+)FoxP3(+) T-regulatory cells (Treg) by flow cytometry.
  
  
  RESULTS
  Seven days after isolated LC, LIS had returned to 0.8 ± 0.4; however, after LCHS/CS healing is significantly delayed (7.2 ± 2.2; P < .05). Addition of MSC to LCHS/CS decreased LIS to 2.0 ± 1.3 (P < .05) and decreased all subgroup scores (inflammatory cells, interstitial and pulmonary edema, and alveolar integrity) significantly compared with LCHS/CS (P < .05). The percentage of Tregs found in the peripheral blood of animals undergoing LCHS/CS did not change from LC alone (10.5 ± 3.3% vs 6.7 ± 1.7%; P > .05). Treatment with MSCs significantly increased the Treg population compared with LCHS/CS alone (11.7 ± 2.7% vs 6.7 ± 1.7%; P < .05) CONCLUSION: In this model, severe impairment of wound healing observed 1 week after LCHS/CS is reversed by a single treatment with MSCs immediately after resuscitation. This improvement in lung healing is associated with a decrease in the number of inflammatory cells and lung edema and a significant increase in peripheral Tregs. Further study into the timing of administration and mechanisms by which cell-based therapy using MSCs modulate the immune system and improve wound healing is warranted.
authors.affiliation: Department of Surgery, Division of Trauma and Surgical Critical Care, Rutgers - New Jersey Medical School, Newark, NJ.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Gore
authors.affiliation: Department of Surgery, Division of Trauma and Surgical Critical Care, Rutgers - New Jersey Medical School, Newark, NJ.
authors.forename: Letitia E
authors.initials: LE
authors.lastname: Bible
authors.affiliation: Department of Surgery, Division of Trauma and Surgical Critical Care, Rutgers - New Jersey Medical School, Newark, NJ.
authors.forename: David H
authors.initials: DH
authors.lastname: Livingston
authors.affiliation: Department of Surgery, Division of Trauma and Surgical Critical Care, Rutgers - New Jersey Medical School, Newark, NJ.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
authors.affiliation: Department of Surgery, Division of Trauma and Surgical Critical Care, Rutgers - New Jersey Medical School, Newark, NJ. Electronic address: sifrizi@njms.rutgers.edu.
authors.forename: Ziad C
authors.initials: ZC
authors.lastname: Sifri
mesh_terms: D000818:Animals; D003288:Contusions / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008168:Lung / Q000378:metabolism*; D055370:Lung Injury / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications*; D013315:Stress, Psychological / Q000150:complications*; D016896:Treatment Outcome; D014945:Wound Healing
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