Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model

Yunge Zhao, Jacob R. Gillen, David A. Harris, Irving L. Kron, Michael Murphy, Christine L. Lau

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Bone marrow-derived mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury. Recently, placenta-derived human mesenchymal stem cells (PMSCs) have shown similarities with bone marrow-derived MSCs in terms of regenerative capabilities and immunogenicity. This study investigates the hypothesis that treatment with PMSCs reduces the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model. Methods: A murine heterotopic tracheal transplant model was used to study the continuum from acute to chronic rejection. In the treatment groups, PMSCs or PMSC-conditioned medium (PMSCCM) were injected either locally or intratracheally into the allograft. Phosphate-buffered saline (PBS) or blank medium was injected in the control groups. Tracheal luminal obliteration was assessed on sections stained with hematoxylin and eosin. Infiltration of inflammatory and immune cells and epithelial progenitor cells was assessed using immunohistochemistry and densitometric analysis. Results: Compared with injection of PBS, local injection of PMSCs significantly reduced luminal obliteration at 28 days after transplantation (P =.015). Intratracheal injection of PMSCs showed similar results to local injection of PMSCs compared with injection of PBS and blank medium (P =.022). Tracheas treated with PMSC/PMSCCM showed protection against the loss of epithelium on day 14, with an increase in P63+CK14+ epithelial progenitor cells and Foxp3+ regulatory T cells. In addition, injection of PMSCs and PMSCCM significantly reduced the number of neutrophils and CD3+ T cells on day 14. Conclusions: This study demonstrates that treatment with PMSCs is protective against the development of bronchiolitis obliterans in an heterotopic tracheal transplant model. These results indicate that PMSCs could provide a novel therapeutic option to reduce chronic rejection after lung transplant.

Original languageEnglish
JournalJournal of Thoracic and Cardiovascular Surgery
Volume147
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Bronchiolitis Obliterans
Mesenchymal Stromal Cells
Placenta
Injections
Therapeutics
Conditioned Culture Medium
Transplants
Phosphates
Stem Cells
Bone Marrow
Epithelial Cells
Acute Lung Injury
Regulatory T-Lymphocytes
Hematoxylin
Eosine Yellowish-(YS)
Trachea
Allografts

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

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Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model. / Zhao, Yunge; Gillen, Jacob R.; Harris, David A.; Kron, Irving L.; Murphy, Michael; Lau, Christine L.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 147, No. 5, 2014.

Research output: Contribution to journalArticle

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