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Stem cell secretome attenuates acute rejection in rat lung allotransplant.
Interact Cardiovasc Thorac Surg. 2019 05 01; 28(5):812-818.IC

Abstract

OBJECTIVES

Stem cells secrete significant amounts of bioactive factors in their secretome that can be immunosuppressive. We studied the effect of the secretome obtained from bone marrow-derived mesenchymal stem cells (BMSC-sec) in combination with cyclosporine A following acute rejection of lung allografts in the rat.

METHODS

Lung allotransplants were performed from male Brown Norway donor rats to recipient male Fisher 344 rats. Rat BMSC-sec was introduced intratracheally in the recipient every day after the transplant until the day the animal was sacrificed. Group A (n = 5) received control medium and cyclosporine A (2.5 mg/kg body weight intraperitoneally) for 5 days post-transplant and group B (n = 5) received BMSC-sec and cyclosporine A. Blood gas analysis was performed to assess graft function at day 5 only from the graft, and the tissue was sampled for measurement of the wet/dry ratio and histological grading of rejection.

RESULTS

All control animals (group A) showed severe signs of rejection. At day 5 grafts in group B showed improved gas exchange (i.e. mean PaO2 mmHg 237.9 ± 130 mmHg vs 24.9 ± 7.8 mmHg in group A). Histological examination according to the International Society of Heart and Lung Transplantation (ISHLT) revealed moderate to severe rejection in all animals in group A (III B) and a significant improvement in group B (I-IIA). The wet/dry ratio was also reduced in group B to 6.19 ± 0.6 compared to 9.36 ± 2 in group A. Furthermore, in vitro T-cell proliferation was reduced after treatment with BMSC-sec for CD 3 cells (69.55 ± 07 vs 73 ± 0.84), for CD 4 (24.95 ± 1.2 vs 27.75 ± 0.21) and for CD 8 cells (3.75 ± 0.2 vs 5.68 ± 0.02).

CONCLUSIONS

The BMSC-sec is a promising novel cell-based therapeutic option for acute rejection in a rat lung allograft model.

Authors+Show Affiliations

Department of General Thoracic Surgery, University Hospital Bern, Bern, Switzerland. Department of General Thoracic Surgery and Lung Transplantation, Pomeranian Medical University, Szczecin, Poland. Department for Biomedical Research, University of Bern, Bern, Switzerland.Department for Biomedical Research, University of Bern, Bern, Switzerland. Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland.Department of General Thoracic Surgery, University Hospital Bern, Bern, Switzerland. Department for Biomedical Research, University of Bern, Bern, Switzerland. Graduate School, University of Bern, Bern, Switzerland.Department for Biomedical Research, University of Bern, Bern, Switzerland.Department for Biomedical Research, University of Bern, Bern, Switzerland.Department of General Thoracic Surgery, University Hospital Bern, Bern, Switzerland. Department for Biomedical Research, University of Bern, Bern, Switzerland.Promed AG, Freiburg, Freiburg Switzerland.Department of General Thoracic Surgery and Lung Transplantation, Pomeranian Medical University, Szczecin, Poland.Department for Biomedical Research, University of Bern, Bern, Switzerland.Department for Biomedical Research, University of Bern, Bern, Switzerland. Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland.Department for Biomedical Research, University of Bern, Bern, Switzerland. Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland.Department of General Thoracic Surgery, University Hospital Bern, Bern, Switzerland. Department for Biomedical Research, University of Bern, Bern, Switzerland.Department for Biomedical Research, University of Bern, Bern, Switzerland. Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30508108

Citation

Pieróg, Jarosław, et al. "Stem Cell Secretome Attenuates Acute Rejection in Rat Lung Allotransplant." Interactive Cardiovascular and Thoracic Surgery, vol. 28, no. 5, 2019, pp. 812-818.
Pieróg J, Fytianos K, Tamò L, et al. Stem cell secretome attenuates acute rejection in rat lung allotransplant. Interact Cardiovasc Thorac Surg. 2019;28(5):812-818.
Pieróg, J., Fytianos, K., Tamò, L., Simillion, C., Taddeo, A., Kocher, G., Gugger, M., Grodzki, T., Heller, M., Blank, F., Geiser, T., Schmid, R. A., & Gazdhar, A. (2019). Stem cell secretome attenuates acute rejection in rat lung allotransplant. Interactive Cardiovascular and Thoracic Surgery, 28(5), 812-818. https://doi.org/10.1093/icvts/ivy306
Pieróg J, et al. Stem Cell Secretome Attenuates Acute Rejection in Rat Lung Allotransplant. Interact Cardiovasc Thorac Surg. 2019 05 1;28(5):812-818. PubMed PMID: 30508108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stem cell secretome attenuates acute rejection in rat lung allotransplant. AU - Pieróg,Jarosław, AU - Fytianos,Kleanthis, AU - Tamò,Luca, AU - Simillion,Cedric, AU - Taddeo,Adriano, AU - Kocher,Gregor, AU - Gugger,Mathias, AU - Grodzki,Tomasz, AU - Heller,Manfred, AU - Blank,Fabian, AU - Geiser,Thomas, AU - Schmid,Ralph A, AU - Gazdhar,Amiq, PY - 2018/07/24/received PY - 2018/09/06/revised PY - 2018/09/23/accepted PY - 2018/12/7/pubmed PY - 2020/1/14/medline PY - 2018/12/4/entrez KW - Acute rejection KW - Lung transplantation KW - Paracrine factors KW - Secretome KW - Stem cells SP - 812 EP - 818 JF - Interactive cardiovascular and thoracic surgery JO - Interact Cardiovasc Thorac Surg VL - 28 IS - 5 N2 - OBJECTIVES: Stem cells secrete significant amounts of bioactive factors in their secretome that can be immunosuppressive. We studied the effect of the secretome obtained from bone marrow-derived mesenchymal stem cells (BMSC-sec) in combination with cyclosporine A following acute rejection of lung allografts in the rat. METHODS: Lung allotransplants were performed from male Brown Norway donor rats to recipient male Fisher 344 rats. Rat BMSC-sec was introduced intratracheally in the recipient every day after the transplant until the day the animal was sacrificed. Group A (n = 5) received control medium and cyclosporine A (2.5 mg/kg body weight intraperitoneally) for 5 days post-transplant and group B (n = 5) received BMSC-sec and cyclosporine A. Blood gas analysis was performed to assess graft function at day 5 only from the graft, and the tissue was sampled for measurement of the wet/dry ratio and histological grading of rejection. RESULTS: All control animals (group A) showed severe signs of rejection. At day 5 grafts in group B showed improved gas exchange (i.e. mean PaO2 mmHg 237.9 ± 130 mmHg vs 24.9 ± 7.8 mmHg in group A). Histological examination according to the International Society of Heart and Lung Transplantation (ISHLT) revealed moderate to severe rejection in all animals in group A (III B) and a significant improvement in group B (I-IIA). The wet/dry ratio was also reduced in group B to 6.19 ± 0.6 compared to 9.36 ± 2 in group A. Furthermore, in vitro T-cell proliferation was reduced after treatment with BMSC-sec for CD 3 cells (69.55 ± 07 vs 73 ± 0.84), for CD 4 (24.95 ± 1.2 vs 27.75 ± 0.21) and for CD 8 cells (3.75 ± 0.2 vs 5.68 ± 0.02). CONCLUSIONS: The BMSC-sec is a promising novel cell-based therapeutic option for acute rejection in a rat lung allograft model. SN - 1569-9285 UR - https://www.unboundmedicine.com/medline/citation/30508108/Stem_cell_secretome_attenuates_acute_rejection_in_rat_lung_allotransplant_ L2 - https://academic.oup.com/icvts/article-lookup/doi/10.1093/icvts/ivy306 DB - PRIME DP - Unbound Medicine ER -