Kinetic and Angiogenic Activity of Circulating Endothelial Colony Forming Cells in Patients with Infantile Haemangioma Receiving Propranolol

Rita Campanelli; Alessia Claudia Codazzi; Valentina Poletto; Carlotta Abbà; Paolo Catarsi; Gabriela Fois; Maria Antonietta Avanzini; Valeria Brazzelli; Chryssoula Tzialla; Annalisa De Silvestri; Carmine Tinelli; Amelia Licari; Roberto Berra-Romani; Estella Zuccolo; Francesco Moccia; Savina Mannarino; Vittorio Rosti; Margherita Massa

doi:10.1055/s-0038-1676855

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2019; 119(02): 274-284
DOI: 10.1055/s-0038-1676855

Endothelium and Angiogenesis

Georg Thieme Verlag KG Stuttgart · New York

Kinetic and Angiogenic Activity of Circulating Endothelial Colony Forming Cells in Patients with Infantile Haemangioma Receiving Propranolol

Rita Campanelli^*

¹Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Alessia Claudia Codazzi^*

²Cardiology Clinic of Pediatrics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Valentina Poletto

¹Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Carlotta Abbà

¹Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Paolo Catarsi

¹Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Gabriela Fois

¹Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Maria Antonietta Avanzini

³Immunology and Transplantation Laboratory/Cell Factory/Pediatric Haematology/Oncology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Valeria Brazzelli

⁴Department of Clinical-Surgical, Diagnostic and Pediatric Science, Institute of Dermatology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Chryssoula Tzialla

⁵Neonatal Intensive Care Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Annalisa De Silvestri

⁶Epidemiology Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Carmine Tinelli

⁶Epidemiology Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Amelia Licari

⁷Department of Pediatrics, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

,

Roberto Berra-Romani

⁸Department of Biomedicine, School of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla, México

,

Estella Zuccolo

⁹Laboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Pavia, Italy

,

Francesco Moccia

⁹Laboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Pavia, Italy

,

Savina Mannarino

²Cardiology Clinic of Pediatrics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Vittorio Rosti

¹Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

,

Margherita Massa

¹⁰Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

› Author Affiliations

Abstract

Endothelial progenitor cells (EPCs) have been suggested to contribute to the neovascularization of infantile haemangioma (IH). There is strong evidence of the efficacy of propranolol in the treatment of IH, possibly by inhibiting both vasculogenesis and angiogenesis in the tumour. We evaluate the frequency of circulating endothelial colony forming cells (ECFCs), as the best EPC surrogate, in patients with IH at diagnosis and while receiving propranolol by an ex vivo 12-month longitudinal study. Biological aspects of the ECFCs, such as their in vitro angiogenic potential, membrane CXCR4 expression and Ca²⁺ signalling, were investigated. Circulating ECFCs were isolated by in vitro culture and expanded for 2 to 3 passages in 23 patients with IH (median age: 5.5 months, range: 5.5 weeks–11 months) before and 3, 6, 9 and 12 months after receiving propranolol. Twenty-four healthy subjects comparable for age were also assessed (CTRLs). Untreated patients with IH had a circulating ECFC frequency lower (p = 0.001) than CTRLs; nevertheless, in in vitro starving conditions, ECFCs showed enhanced capacity to form tube-like structures than those of CTRLs. Patients with IH following the therapy with propranolol had a significantly increased (p = 0.022) circulating ECFC frequency, that showed a diminished tube-like formation capacity in vitro, and an altered constitutive store-operated Ca²⁺ entry. ECFCs play a role in IH pathogenesis; the response to propranolol therapy is associated with their increased frequency in the peripheral blood and a reduction of their vasculogenic activity.

Keywords

endothelial progenitor cells - endothelial colony forming cells - angiogenesis - infantile haemangioma - propranolol

Full Text

References

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Supplementary Material

Supplementary Material