Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts
Obliterative bronchiolitis (OB) remains the most significant cause of death in long-term survival of lung transplantation. Using an established murine heterotopic tracheal allograft model, the effects of different routes of administration of bone marrow-derived multipotent stromal cells (MSCs) on th...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2014/468927 |
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| author | Alicia Casey Fabian Dirks Olin D. Liang Hakima Harrach Katharina Schuette-Nuetgen Kristen Leeman Carla F. Kim Craig Gerard Meera Subramaniam |
| author_facet | Alicia Casey Fabian Dirks Olin D. Liang Hakima Harrach Katharina Schuette-Nuetgen Kristen Leeman Carla F. Kim Craig Gerard Meera Subramaniam |
| author_sort | Alicia Casey |
| collection | DOAJ |
| description | Obliterative bronchiolitis (OB) remains the most significant cause of death in long-term survival of lung transplantation. Using an established murine heterotopic tracheal allograft model, the effects of different routes of administration of bone marrow-derived multipotent stromal cells (MSCs) on the development of OB were evaluated. Tracheas from BALB/c mice were implanted into the subcutaneous tissue of major histocompatibility complex- (MHC-) disparate C57BL/6 mice. At the time of transplant, bone marrow-derived MSCs were administered either systemically or locally or via a combination of the two routes. The allografts were explanted at various time points after transplantation and were evaluated for epithelial integrity, inflammatory cell infiltration, fibrosis, and luminal obliteration. We found that the most effective route of bone marrow-derived MSC administration is the combination of systemic and local delivery. Treatment of recipient mice with MSCs suppressed neutrophil, macrophage, and T-cell infiltration and reduced fibrosis. These beneficial effects were observed despite lack of significant MSC epithelial engraftment or new epithelial cell generation. Our study suggests that optimal combination of systemic and local delivery of MSCs may ameliorate the development of obliterative airway disease through modulation of immune response. |
| format | Article |
| id | doaj-art-e57ffa0d5d934c65a2937cc627322801 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-e57ffa0d5d934c65a2937cc6273228012025-02-03T06:13:59ZengWileyStem Cells International1687-966X1687-96782014-01-01201410.1155/2014/468927468927Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal AllograftsAlicia Casey0Fabian Dirks1Olin D. Liang2Hakima Harrach3Katharina Schuette-Nuetgen4Kristen Leeman5Carla F. Kim6Craig Gerard7Meera Subramaniam8Division of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USADivision of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USADivision of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USADivision of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USADivision of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USADivision of Newborn Medicine, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USAStem Cell Program, Boston Children’s Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02115, USADivision of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USADivision of Respiratory Diseases, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 4, Boston, MA 02115, USAObliterative bronchiolitis (OB) remains the most significant cause of death in long-term survival of lung transplantation. Using an established murine heterotopic tracheal allograft model, the effects of different routes of administration of bone marrow-derived multipotent stromal cells (MSCs) on the development of OB were evaluated. Tracheas from BALB/c mice were implanted into the subcutaneous tissue of major histocompatibility complex- (MHC-) disparate C57BL/6 mice. At the time of transplant, bone marrow-derived MSCs were administered either systemically or locally or via a combination of the two routes. The allografts were explanted at various time points after transplantation and were evaluated for epithelial integrity, inflammatory cell infiltration, fibrosis, and luminal obliteration. We found that the most effective route of bone marrow-derived MSC administration is the combination of systemic and local delivery. Treatment of recipient mice with MSCs suppressed neutrophil, macrophage, and T-cell infiltration and reduced fibrosis. These beneficial effects were observed despite lack of significant MSC epithelial engraftment or new epithelial cell generation. Our study suggests that optimal combination of systemic and local delivery of MSCs may ameliorate the development of obliterative airway disease through modulation of immune response.http://dx.doi.org/10.1155/2014/468927 |
| spellingShingle | Alicia Casey Fabian Dirks Olin D. Liang Hakima Harrach Katharina Schuette-Nuetgen Kristen Leeman Carla F. Kim Craig Gerard Meera Subramaniam Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts Stem Cells International |
| title | Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts |
| title_full | Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts |
| title_fullStr | Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts |
| title_full_unstemmed | Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts |
| title_short | Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts |
| title_sort | bone marrow derived multipotent stromal cells attenuate inflammation in obliterative airway disease in mouse tracheal allografts |
| url | http://dx.doi.org/10.1155/2014/468927 |
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