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*
1  Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Alessia Claudia Codazzi*
2  Cardiology Clinic of Pediatrics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Valentina Poletto
1  Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Carlotta Abbà
1  Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Paolo Catarsi
1  Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Gabriela Fois
1  Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Maria Antonietta Avanzini
3  Immunology and Transplantation Laboratory/Cell Factory/Pediatric Haematology/Oncology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Valeria Brazzelli
4  Department of Clinical-Surgical, Diagnostic and Pediatric Science, Institute of Dermatology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Chryssoula Tzialla
5  Neonatal Intensive Care Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Annalisa De Silvestri
6  Epidemiology Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Carmine Tinelli
6  Epidemiology Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Amelia Licari
7  Department of Pediatrics, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
,
Roberto Berra-Romani
8  Department of Biomedicine, School of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla, México
,
Estella Zuccolo
9  Laboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Pavia, Italy
,
Francesco Moccia
9  Laboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani,” University of Pavia, Pavia, Italy
,
Savina Mannarino
2  Cardiology Clinic of Pediatrics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Vittorio Rosti
1  Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
,
Margherita Massa
10  Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
› Author Affiliations
Funding The present project was financially supported by the intramural funding program “Ricerca Corrente” of the IRCCS Policlinico San Matteo Foundation: RC/80520 to M. Massa.
Further Information

Publication History

18 July 2018

15 November 2018

Publication Date:
04 January 2019 (eFirst)

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.

* These authors equally contributed to the manuscript.


Supplementary Material