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Published on: September 18, 2017
Circulating Mesenchymal Stromal Cells in Patients with Infantile Hemangioma: Evaluation of Their Functional Capacity
Carlotta Abbà1, Stefania Croce2, Chiara Valsecchi2
1General Medicine 2-Center for Systemic Amyloidosis and High-Complexity Diseases, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy.
Insights
Circulating mesenchymal stem cells (cMSCs) in infantile hemangioma (IH) patients fuel tumor growth with pro-angiogenic and inflammatory properties. Propranolol therapy normalizes cMSC function, suggesting them as a therapeutic target.
Area of Science:
- Vascular Biology
- Stem Cell Biology
- Pediatric Oncology
Background:
- Infantile hemangioma (IH) is a common pediatric vascular tumor.
- Colony-forming unit-fibroblasts (CFU-Fs) in peripheral blood (PB) of IH patients were previously identified.
- The precise nature and role of these CFU-Fs in IH pathogenesis remain to be fully elucidated.
Purpose of the Study:
- To characterize CFU-Fs from IH patients and healthy controls.
- To investigate the potential role of these cells in IH pathogenesis.
- To evaluate the impact of propranolol therapy on these cells.
Main Methods:
- Phenotypic analysis of CFU-Fs using flow cytometry.
- Assessment of differentiation capacity (adipogenesis) and pro-angiogenic potential via in vitro cultures.
- Gene expression profiling using RT-PCR.
Main Results:
- CFU-Fs were identified as circulating mesenchymal stem cells (cMSCs).
- At disease onset, IH patient cMSCs exhibited reduced adipogenic potential and enhanced in vitro angiogenesis support.
- Elevated inflammatory (IL1β, ESM1) and angiogenic (F3) gene expression was observed in cMSCs from IH patients compared to controls.
- One-year propranolol therapy improved cMSC adipogenic differentiation and abolished their pro-angiogenic activity in vitro.
- Post-therapy, cMSC gene expression profiles normalized, showing no significant differences compared to controls.
Conclusions:
- Reduced adipogenic potential, pro-angiogenic activity, and inflammatory/angiogenic gene expression of cMSCs in IH patients may contribute to tumor growth.
- Propranolol therapy significantly alters cMSC characteristics, indicating cMSCs as a potential therapeutic target for infantile hemangioma.
Abstract:
We previously published that in patients with infantile hemangioma (IH) at the onset (T0) colony forming unit-fibroblasts (CFU-Fs) are present in in vitro cultures from PB. Herein, we characterize these CFU-Fs and investigate their potential role in IH pathogenesis, before and after propranolol therapy. The CFU-F phenotype (by flow cytometry), their differentiation capacity and ability to support angiogenesis (by in vitro cultures) and their gene expression (by RT-PCR) were evaluated. We found that CFU-Fs are actual circulating MSCs (cMSCs). In patients at T0, cMSCs had reduced adipogenic potential, supported the formation of tube-like structures in vitro and showed either inflammatory (IL1β and ESM1) or angiogenic (F3) gene expression higher than that of cMSCs from CTRLs. In patients receiving one-year propranolol therapy, the cMSC differentiation in adipocytes improved, while their support in in vitro tube-like formation was lost; no difference was found between patient and CTRL cMSC gene expressions. In conclusion, in patients with IH at T0 the cMSC reduced adipogenic potential, their support in angiogenic activity and the inflammatory/angiogenic gene expression may fuel the tumor growth. One-year propranolol therapy modifies this picture, suggesting cMSCs as one of the drug targets.
