Evolving technology/basic science
Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model

https://doi.org/10.1016/j.jtcvs.2013.09.041Get rights and content
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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.

CTSNet classification

12
15

Abbreviations and Acronyms

BO
bronchiolitis obliterans
DAPI
4,6-diamidine-2-phenylindole dihydrochloride
G-CSF
granulocyte colony-stimulating factor
GM-CSF
granulocyte macrophage colony-stimulating factor
H&E
hematoxylin and eosin
HPF
high-power field
HTT
heterotopic tracheal transplant
IL
interleukin
IL-1RA
interleukin 1 receptor antagonist
MSC
mesenchymal stem cells
PBS
phosphate-buffered saline
PMSC
placenta-derived human mesenchymal stem cells
PMSCCM
PMSC-conditioned medium
TNF
tumor necrosis factor

Cited by (0)

C.L.L. is supported by a grant sponsored by the National Heart, Lung, and Blood Institute (1K08HL094704) and matching funds from the Thoracic Surgery Foundation for Research and Education. I.L.K. is supported by a grant sponsored by the National Institute of Health (5RO1HL092953). J.R.G. and is supported by a training grant under I.L.K sponsored by the National Institute of Health (NIH T32HL007849).

Disclosures: Authors have nothing to disclose with regard to commercial support.