Cyclosporine decreases vascular progenitor cell numbers after cardiac transplantation and attenuates progenitor cell growth in vitro

William R. Davies, Shaohua Wang, Keiji Oi, Kent R Bailey, Henry D. Tazelaar, Noel M. Caplice, Christopher G A McGregor

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objective: Recent experimental evidence suggests that the neointimal proliferation seen in cardiac allograft vasculopathy may in part derive from recipient progenitor cells. The effect of cyclosporine on these circulating progenitors in the setting of cardiac transplantation is currently unknown. Methods: Three surgical series were performed: sham operation alone, sham operation with immunosuppression, and heterotopic porcine cardiac transplantation with immunosuppression. The sham operation involved laparotomy and consecutive clamping of the abdominal aorta and inferior vena cava. Post-operative immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml) and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC CFU) and smooth muscle outgrowth colony numbers (SOC CFU) were quantified weekly for 4 weeks post-operatively. A series of in vitro experiments were performed to determine the effect of cyclosporine on the differentiation, migration, and proliferation of EOCs and SOCs. Results: In the sham alone series there were no changes to either EOC CFU or SOC CFU. In the sham with immunosuppression and the transplant series, both EOC CFU and SOC CFU fell in the first 2 weeks (p < 0.05) compared with baseline (EOC CFU, 3.4 ± 0.6; SOC CFU, 11.1 ± 2.8). EOC CFU recovered at 4 weeks to above baseline levels in the sham immunosuppression group only (15.2 ± 3.9; p = 0.01). SOC CFU showed no recovery in the immunosuppression groups. Cyclosporine, even at a low dose, prevented differentiation, inhibited proliferation, and attenuated migration of both EOCs and SOCs. Conclusion: Immunosuppression in the setting of cardiac transplantation causes a profound reduction in circulating progenitor cells capable of differentiating into endothelial and smooth muscle cells. This effect can in part be explained by the inhibitory effects of cyclosporine on progenitor growth and differentiation seen in this study.

Original languageEnglish (US)
Pages (from-to)1868-1877
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume24
Issue number11
DOIs
StatePublished - Nov 2005

Fingerprint

Heart Transplantation
Immunosuppression
Cyclosporine
Blood Vessels
Stem Cells
Cell Count
Growth
Abdominal Aorta
Methylprednisolone
Inferior Vena Cava
In Vitro Techniques
Constriction
Laparotomy
Smooth Muscle Myocytes
Allografts
Smooth Muscle
Swine
Transplants

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Cyclosporine decreases vascular progenitor cell numbers after cardiac transplantation and attenuates progenitor cell growth in vitro. / Davies, William R.; Wang, Shaohua; Oi, Keiji; Bailey, Kent R; Tazelaar, Henry D.; Caplice, Noel M.; McGregor, Christopher G A.

In: Journal of Heart and Lung Transplantation, Vol. 24, No. 11, 11.2005, p. 1868-1877.

Research output: Contribution to journalArticle

Davies, William R. ; Wang, Shaohua ; Oi, Keiji ; Bailey, Kent R ; Tazelaar, Henry D. ; Caplice, Noel M. ; McGregor, Christopher G A. / Cyclosporine decreases vascular progenitor cell numbers after cardiac transplantation and attenuates progenitor cell growth in vitro. In: Journal of Heart and Lung Transplantation. 2005 ; Vol. 24, No. 11. pp. 1868-1877.
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abstract = "Objective: Recent experimental evidence suggests that the neointimal proliferation seen in cardiac allograft vasculopathy may in part derive from recipient progenitor cells. The effect of cyclosporine on these circulating progenitors in the setting of cardiac transplantation is currently unknown. Methods: Three surgical series were performed: sham operation alone, sham operation with immunosuppression, and heterotopic porcine cardiac transplantation with immunosuppression. The sham operation involved laparotomy and consecutive clamping of the abdominal aorta and inferior vena cava. Post-operative immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml) and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC CFU) and smooth muscle outgrowth colony numbers (SOC CFU) were quantified weekly for 4 weeks post-operatively. A series of in vitro experiments were performed to determine the effect of cyclosporine on the differentiation, migration, and proliferation of EOCs and SOCs. Results: In the sham alone series there were no changes to either EOC CFU or SOC CFU. In the sham with immunosuppression and the transplant series, both EOC CFU and SOC CFU fell in the first 2 weeks (p < 0.05) compared with baseline (EOC CFU, 3.4 ± 0.6; SOC CFU, 11.1 ± 2.8). EOC CFU recovered at 4 weeks to above baseline levels in the sham immunosuppression group only (15.2 ± 3.9; p = 0.01). SOC CFU showed no recovery in the immunosuppression groups. Cyclosporine, even at a low dose, prevented differentiation, inhibited proliferation, and attenuated migration of both EOCs and SOCs. Conclusion: Immunosuppression in the setting of cardiac transplantation causes a profound reduction in circulating progenitor cells capable of differentiating into endothelial and smooth muscle cells. This effect can in part be explained by the inhibitory effects of cyclosporine on progenitor growth and differentiation seen in this study.",
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AU - Davies, William R.

AU - Wang, Shaohua

AU - Oi, Keiji

AU - Bailey, Kent R

AU - Tazelaar, Henry D.

AU - Caplice, Noel M.

AU - McGregor, Christopher G A

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N2 - Objective: Recent experimental evidence suggests that the neointimal proliferation seen in cardiac allograft vasculopathy may in part derive from recipient progenitor cells. The effect of cyclosporine on these circulating progenitors in the setting of cardiac transplantation is currently unknown. Methods: Three surgical series were performed: sham operation alone, sham operation with immunosuppression, and heterotopic porcine cardiac transplantation with immunosuppression. The sham operation involved laparotomy and consecutive clamping of the abdominal aorta and inferior vena cava. Post-operative immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml) and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC CFU) and smooth muscle outgrowth colony numbers (SOC CFU) were quantified weekly for 4 weeks post-operatively. A series of in vitro experiments were performed to determine the effect of cyclosporine on the differentiation, migration, and proliferation of EOCs and SOCs. Results: In the sham alone series there were no changes to either EOC CFU or SOC CFU. In the sham with immunosuppression and the transplant series, both EOC CFU and SOC CFU fell in the first 2 weeks (p < 0.05) compared with baseline (EOC CFU, 3.4 ± 0.6; SOC CFU, 11.1 ± 2.8). EOC CFU recovered at 4 weeks to above baseline levels in the sham immunosuppression group only (15.2 ± 3.9; p = 0.01). SOC CFU showed no recovery in the immunosuppression groups. Cyclosporine, even at a low dose, prevented differentiation, inhibited proliferation, and attenuated migration of both EOCs and SOCs. Conclusion: Immunosuppression in the setting of cardiac transplantation causes a profound reduction in circulating progenitor cells capable of differentiating into endothelial and smooth muscle cells. This effect can in part be explained by the inhibitory effects of cyclosporine on progenitor growth and differentiation seen in this study.

AB - Objective: Recent experimental evidence suggests that the neointimal proliferation seen in cardiac allograft vasculopathy may in part derive from recipient progenitor cells. The effect of cyclosporine on these circulating progenitors in the setting of cardiac transplantation is currently unknown. Methods: Three surgical series were performed: sham operation alone, sham operation with immunosuppression, and heterotopic porcine cardiac transplantation with immunosuppression. The sham operation involved laparotomy and consecutive clamping of the abdominal aorta and inferior vena cava. Post-operative immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml) and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC CFU) and smooth muscle outgrowth colony numbers (SOC CFU) were quantified weekly for 4 weeks post-operatively. A series of in vitro experiments were performed to determine the effect of cyclosporine on the differentiation, migration, and proliferation of EOCs and SOCs. Results: In the sham alone series there were no changes to either EOC CFU or SOC CFU. In the sham with immunosuppression and the transplant series, both EOC CFU and SOC CFU fell in the first 2 weeks (p < 0.05) compared with baseline (EOC CFU, 3.4 ± 0.6; SOC CFU, 11.1 ± 2.8). EOC CFU recovered at 4 weeks to above baseline levels in the sham immunosuppression group only (15.2 ± 3.9; p = 0.01). SOC CFU showed no recovery in the immunosuppression groups. Cyclosporine, even at a low dose, prevented differentiation, inhibited proliferation, and attenuated migration of both EOCs and SOCs. Conclusion: Immunosuppression in the setting of cardiac transplantation causes a profound reduction in circulating progenitor cells capable of differentiating into endothelial and smooth muscle cells. This effect can in part be explained by the inhibitory effects of cyclosporine on progenitor growth and differentiation seen in this study.

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