Modulation of adipose-derived stem cell behavior by prostate pathology-associated plasma: insights from in vitro exposure

前列腺病理相关血浆对脂肪干细胞行为的调节:从体外暴露中获得的见解

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作者:Sara Cruciani #, Donatella Coradduzza #, Francesca Balzano, Giuseppe Garroni, Emanuela Azara, Renzo Pala, Alessandro P Delitala, Massimo Madonia, Alessandro Tedde, Giampiero Capobianco, Marco Petrillo, Cecilia Angelucci, Ciriaco Carru, Carlo Ventura, Margherita Maioli

Abstract

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.

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