Mesangiogenic progenitor cells are forced toward the angiogenic fate, in multiple myeloma
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Simone Pacini1, Marina Montali1, Francesco Mazziotta2, Claudia P. Schifone1, Lucia Macchia3, Vittoria Carnicelli4, Francesca M. Panvini5, Serena Barachini1, Laura Notarfranchi6, Giovanni Battista Previti7, Gabriele Buda1 and Mario Petrini1
1 Department of Clinical and Experimental Medicine, Hematology Division, University of Pisa, Pisa, Italy
2 GeNOMEC School of Doctorate, University of Siena, Siena, Italy
3 Department of Laboratory Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
4 Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
5 Institute of Life Sciences, Sant’Anna School of Advanced Studies, Pisa, Italy
6 Department of Medicine and Surgery, Hematology Division, University of Parma, Parma, Italy
7 Unit of Anesthesia and Intensive Care, University of Sassari, Sassari, Italy
Keywords: multiple myeloma; bone marrow microenvironment; angiogenesis; osteogenesis; mesangiogenic progenitor cells
Received: July 18, 2019 Accepted: October 04, 2019 Published: November 26, 2019
Multiple myeloma (MM) progresses mainly in the bone marrow where the involvement of a specific microenvironment plays a critical role in maintaining plasma cell growth, spread, and survival. In active disease, the switch from a pre-vascular/non-active phase to a vascular phase is coupled with the impairment of bone turnover. Previously, we have isolated Mesangiogenic Progenitor Cells (MPCs), a bone marrow population that showed mesengenic and angiogenic potential, both in vitro and in vivo. MPC differentiation into musculoskeletal tissue and their ability of sprouting angiogenesis are mutually exclusive, suggesting a role in the imbalancing of the microenvironment in multiple myeloma.
MPCs from 32 bone marrow samples of multiple myeloma and 23 non-hematological patients were compared in terms of frequency, phenotype, mesengenic/angiogenic potential, and gene expression profile. Defective osteogenesis was recorded for MM-derived MPCs that showed longer angiogenic sprouting distances respect to non-hematological MPCs, retaining this capability after mesengenic induction. This altered MPCs differentiation potential was not detected in asymptomatic myelomatous disease.
These in vitro experiments are suggestive of a forced angiogenic fate in MPCs isolated from MM patients, which also showed increased sprouting activity. Taking together our results suggest a possible role of these cells in the “angiogenic switch” in the MM micro-environment.
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