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Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression

INTRODUCTION: Adipose tissue (AT) has become a source of mesenchymal stromal/stem cells (MSC) for regenerative medicine applications, in particular skeletal disorders. Several enzymatic or mechanical procedures have been proposed to process AT with the aim to isolate cells that can be locally implan...

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Autores principales: Casari, Giulia, Resca, Elisa, Giorgini, Andrea, Candini, Olivia, Petrachi, Tiziana, Piccinno, Maria Serena, Foppiani, Elisabetta Manuela, Pacchioni, Lucrezia, Starnoni, Marta, Pinelli, Massimo, De Santis, Giorgio, Selleri, Filippo, Catani, Fabio, Dominici, Massimo, Veronesi, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399787/
https://www.ncbi.nlm.nih.gov/pubmed/34454577
http://dx.doi.org/10.1186/s13287-021-02540-1
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author Casari, Giulia
Resca, Elisa
Giorgini, Andrea
Candini, Olivia
Petrachi, Tiziana
Piccinno, Maria Serena
Foppiani, Elisabetta Manuela
Pacchioni, Lucrezia
Starnoni, Marta
Pinelli, Massimo
De Santis, Giorgio
Selleri, Filippo
Catani, Fabio
Dominici, Massimo
Veronesi, Elena
author_facet Casari, Giulia
Resca, Elisa
Giorgini, Andrea
Candini, Olivia
Petrachi, Tiziana
Piccinno, Maria Serena
Foppiani, Elisabetta Manuela
Pacchioni, Lucrezia
Starnoni, Marta
Pinelli, Massimo
De Santis, Giorgio
Selleri, Filippo
Catani, Fabio
Dominici, Massimo
Veronesi, Elena
author_sort Casari, Giulia
collection PubMed
description INTRODUCTION: Adipose tissue (AT) has become a source of mesenchymal stromal/stem cells (MSC) for regenerative medicine applications, in particular skeletal disorders. Several enzymatic or mechanical procedures have been proposed to process AT with the aim to isolate cells that can be locally implanted. How AT is processed may impact its properties. Thus, we compared AT processed by centrifugation (C-AT) to microfragmentation (MF-AT). Focusing on MF-AT, we subsequently assessed the impact of synovial fluid (SF) alone on both MF-AT and isolated AT-MSC to better understand their cartilage repair mechanisms. MATERIALS AND METHODS: MF-AT and C-AT from the same donors were compared by histology and qRT-PCR immediately after isolation or as ex vivo cultures using a micro-tissue pellet system. The in vitro impact of SF on MF-AT and AT-MSC was assessed by histological staining and molecular analysis. RESULTS: The main AT histological features (i.e., increased extracellular matrix and cellularity) of the freshly isolated or ex vivo-cultured MF-AT persisted compared to C-AT, which rapidly deteriorated during culture. Based on our previous studies of HOX genes in MSC, we investigated the involvement of Homeobox Protein HOX-B7 (HOXB7) and its target basic Fibroblast Growth Factor (bFGF) in the molecular mechanism underlying the improved performance of MF-AT. Indeed, both these biomarkers were more prominent in freshly isolated MF-AT compared to C-AT. SF alone preserved the AT histological features of MF-AT, together with HOXB7 and bFGF expression. Increased cell performance was also observed in isolated AT-MSC after SF treatment concomitant with enhanced HOXB7 expression, although there was no apparent association with bFGF. CONCLUSIONS: Our findings show that MF has a positive effect on the maintenance of AT histology and may trigger the expression of trophic factors that improve tissue repair by processed AT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02540-1.
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spelling pubmed-83997872021-08-30 Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression Casari, Giulia Resca, Elisa Giorgini, Andrea Candini, Olivia Petrachi, Tiziana Piccinno, Maria Serena Foppiani, Elisabetta Manuela Pacchioni, Lucrezia Starnoni, Marta Pinelli, Massimo De Santis, Giorgio Selleri, Filippo Catani, Fabio Dominici, Massimo Veronesi, Elena Stem Cell Res Ther Research INTRODUCTION: Adipose tissue (AT) has become a source of mesenchymal stromal/stem cells (MSC) for regenerative medicine applications, in particular skeletal disorders. Several enzymatic or mechanical procedures have been proposed to process AT with the aim to isolate cells that can be locally implanted. How AT is processed may impact its properties. Thus, we compared AT processed by centrifugation (C-AT) to microfragmentation (MF-AT). Focusing on MF-AT, we subsequently assessed the impact of synovial fluid (SF) alone on both MF-AT and isolated AT-MSC to better understand their cartilage repair mechanisms. MATERIALS AND METHODS: MF-AT and C-AT from the same donors were compared by histology and qRT-PCR immediately after isolation or as ex vivo cultures using a micro-tissue pellet system. The in vitro impact of SF on MF-AT and AT-MSC was assessed by histological staining and molecular analysis. RESULTS: The main AT histological features (i.e., increased extracellular matrix and cellularity) of the freshly isolated or ex vivo-cultured MF-AT persisted compared to C-AT, which rapidly deteriorated during culture. Based on our previous studies of HOX genes in MSC, we investigated the involvement of Homeobox Protein HOX-B7 (HOXB7) and its target basic Fibroblast Growth Factor (bFGF) in the molecular mechanism underlying the improved performance of MF-AT. Indeed, both these biomarkers were more prominent in freshly isolated MF-AT compared to C-AT. SF alone preserved the AT histological features of MF-AT, together with HOXB7 and bFGF expression. Increased cell performance was also observed in isolated AT-MSC after SF treatment concomitant with enhanced HOXB7 expression, although there was no apparent association with bFGF. CONCLUSIONS: Our findings show that MF has a positive effect on the maintenance of AT histology and may trigger the expression of trophic factors that improve tissue repair by processed AT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02540-1. BioMed Central 2021-08-28 /pmc/articles/PMC8399787/ /pubmed/34454577 http://dx.doi.org/10.1186/s13287-021-02540-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Casari, Giulia
Resca, Elisa
Giorgini, Andrea
Candini, Olivia
Petrachi, Tiziana
Piccinno, Maria Serena
Foppiani, Elisabetta Manuela
Pacchioni, Lucrezia
Starnoni, Marta
Pinelli, Massimo
De Santis, Giorgio
Selleri, Filippo
Catani, Fabio
Dominici, Massimo
Veronesi, Elena
Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression
title Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression
title_full Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression
title_fullStr Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression
title_full_unstemmed Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression
title_short Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression
title_sort microfragmented adipose tissue is associated with improved ex vivo performance linked to hoxb7 and b-fgf expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399787/
https://www.ncbi.nlm.nih.gov/pubmed/34454577
http://dx.doi.org/10.1186/s13287-021-02540-1
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