학술논문

Transcriptomes of human mesenchymal cells isolated from the right ventricle and epicardial fat differ strikingly both directly after isolation and long-term culture.
Document Type
Academic Journal
Author
Stępniewski J; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Florczyk-Soluch U; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Szade K; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Bukowska-Strakova K; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.; Czapla J; Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.; Matuszczak S; Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.; Jarosz-Biej M; Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.; Langrzyk A; KardioMed Silesia, Zabrze, Poland.; Tomczyk M; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Rumieńczyk I; Department of Genetics, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.; Kulecka M; Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.; Mikuła M; Department of Genetics, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.; Ostrowski J; Department of Genetics, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.; Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.; Jaźwa-Kusior A; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Zembala M; Department of Cardiac Surgery and Transplantology, Silesian Center for Heart Diseases, Zabrze, Poland.; Józkowicz A; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Zembala MO; Department of Cardiac Surgery and Transplantology, Silesian Center for Heart Diseases, Zabrze, Poland.; Dulak J; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; KardioMed Silesia, Zabrze, Poland.
Source
Publisher: John Wiley & Sons Ltd on behalf of the European Society of Cardiology Country of Publication: England NLM ID: 101669191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2055-5822 (Electronic) Linking ISSN: 20555822 NLM ISO Abbreviation: ESC Heart Fail Subsets: MEDLINE
Subject
Language
English
Abstract
Aims: Mesenchymal stromal cells isolated from different tissues are claimed to demonstrate similar therapeutic potential and are often incorrectly named mesenchymal stem cells. However, through comparison of such cells is lacking. This study aimed to compare the transcriptome of mesenchymal cells of the same phenotype isolated from the heart muscle and epicardial fat of the same patient, before and after culture.
Methods and Results: Cells were isolated from biopsies of the right ventricle and epicardial fat collected from five patients (three men and two women, mean age 59.4 ± 2.6) who underwent heart transplantation due to ischaemic cardiomyopathy. In both tissues, immunophenotyping revealed three distinct populations: (i)CD31 - CD45 - CD90 + CD34 + CD146 - , (ii) CD31 - CD45 - CD90 + CD34 - CD146 + , and (iii) CD31 - CD45 - CD90 - CD34 - CD146 + , of which only the first one could be grown after sorting. Material for RNA-seq was collected from these cells before culture (250 cells) and at passage 6 (5000 cells). Transcriptomic analysis revealed that cells of the same phenotype (CD31 - CD45 - CD90 + CD34 + CD146 - ) upon isolation preferentially clustered according to the tissue of origin, not to the patient from whom they were isolated. Genes up-regulated in the right ventricle-derived cells were related to muscle physiology while down-regulated genes included those encoding proteins with transmembrane signalling receptor activity. After six passages, heart-derived and fat-derived cells did not acquire similar transcriptome. Cells isolated from the right ventricle in comparison with their epicardial fat-derived counterparts demonstrated higher level of transcripts related, among others, to RNA processing and muscle development. The down-regulated genes were involved in the nucleosome assembly, DNA packaging and replication, and interleukin-7-mediated signalling pathway. Cells from epicardial fat demonstrated higher heterogeneity both before and after culture. Cell culture significantly changed gene expression profile within both tissues.
Conclusions: This study is an essential indication that mesenchymal cells isolated from different tissues do not demonstrate similar properties. Phenotypic identification and ease of isolation cannot be considered as a criterion in any therapeutic utilization of such cells.
(© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)