The potential of GMP-compliant platelet lysate to induce a permissive state for cardiovascular transdifferentiation in human mediastinal adipose tissue-derived mesenchymal stem cells.
Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy ; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 000161 Rome, Italy.
Camilla
C
Siciliano
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Isotta
I
Chimenti
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Antonella
A
Bordin
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Donatella
D
Ponti
Immunohematology and Transfusion Medicine, San Camillo Forlanini Hospital, Circonvallazione Gianicolense 87, 00152 Rome, Italy.
Paola
P
Iudicone
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Mariangela
M
Peruzzi
Department of Medical-Surgical Science and Translational Medicine, Division of Thoracic Surgery, "Sapienza" University of Rome, Sant'Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy.
Erino Angelo
EA
Rendina
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Antonella
A
Calogero
Immunohematology and Transfusion Medicine, San Camillo Forlanini Hospital, Circonvallazione Gianicolense 87, 00152 Rome, Italy ; Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 000161 Rome, Italy.
Luca
L
Pierelli
Department of Medical-Surgical Science and Translational Medicine, Division of Thoracic Surgery, "Sapienza" University of Rome, Sant'Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy.
Mohsen
M
Ibrahim
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
Elena
E
De Falco
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D001792:Blood Platelets / Q000737:chemistry* / Q000166:cytology; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D017408:Guidelines as Topic; D006801:Humans; D008482:Mediastinum / Q000033:anatomy & histology / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism