Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors

Foppiani, Elisabetta Manuela; Candini, Olivia; Mastrolia, Ilenia; Murgia, Alba; Grisendi, Giulia; Samarelli, Anna Valeria; Boscaini, Giulia; Pacchioni, Lucrezia; Pinelli, Massimo; Santis, Giorgio De; Horwitz, Edwin M.; Veronesi, Elena; Dominici, Massimo

doi:10.1186/s13287-019-1200-6

Cited by 16 publications

(15 citation statements)

References 58 publications

(64 reference statements)

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“…HOXB7 is downregulated in MSC during ageing and positively connected with the increased performance of these cells [ 27 , 28 ]. To investigate the distinct behaviour of the differentially processed AT, HOXB7 expression was evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…The cells themselves may be incorporated into the damaged tissue and differentiate into chondrocytes, or MF-AT may activate reparative mechanisms through specific pathways that influence resident chondrocyte repair, inflammation or both processes. In our previous studies, we showed how genes belonging to the HOXB family are associated with adipose and bone marrow MSC performance (i.e., osteogenesis and chondrogenesis) in association with increased basic Fibroblast Growth Factor (bFGF) [ 27 , 28 ]. In those studies, the role of Homeobox Protein HOX-B7 (HOXB7) as a regulator of skeleton homeostasis was established, suggesting that HOXB7 can affect MSC through a bFGF-mediated autocrine loop [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…MSCs display resistance to TRAIL due to their low expression of both DR4 and DR5 ( Grisendi et al., 2010 ). In addition, is possible to consistently isolate and modify MSCs from human adipose tissue by minimally invasive surgical procedures ( Foppiani et al., 2019 ; Starnoni et al., 2019 ). The wild-type gene coding for membrane-bound TRAIL, as well as modified cassettes expressing soluble ligand forms, have been used in MSC-based therapeutic strategies, demonstrating antitumor effects in vitro and in vivo in a wide variety of human solid neoplasms, including lung cancer, pancreatic cancer, glioblastoma, sarcoma, and hepatocarcinoma ( Loebinger et al., 2009 ; Sasportas LS et al., 2009 ; Grisendi et al., 2010 ; Grisendi et al., 2011 ; Yan et al., 2014 ; D’Souza et al., 2015 ; Grisendi et al., 2015 ; Guiho et al., 2016 ; Golinelli et al., 2018 ; Candini et al., 2019 ; Rossignoli et al., 2019 ; Spano et al., 2019 ).…”

Section: Genetic Modification Of Mscs To Target Cancermentioning

confidence: 99%

Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?

et al. 2020

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Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation.

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“…Genetic engineering of MSCs has been studied in the past years with the purpose of enhancing the therapeutic potential of these cells and improving the outcomes after transplantation. This has been achieved using non-viral or viral vectors to induce the expression of different factors, depending on the desired results, such as increasing their survival and proliferation rate and improving their pro-regenerative capacity (Sage et al, 2016;Foppiani et al, 2019). In this review, we discuss the current methods employed in the generation of genetically modified MSCs and the results obtained with the expression of different factors and the main disease settings in which this modality of cell and gene therapy has been investigated.…”

Section: Introductionmentioning

confidence: 99%

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

Damasceno

Santana

Santos

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stem/stromal cells (MSCs) have been widely studied in the field of regenerative medicine for applications in the treatment of several disease settings. The therapeutic potential of MSCs has been evaluated in studies in vitro and in vivo, especially based on their anti-inflammatory and pro-regenerative action, through the secretion of soluble mediators. In many cases, however, insufficient engraftment and limited beneficial effects of MSCs indicate the need of approaches to enhance their survival, migration and therapeutic potential. Genetic engineering emerges as a means to induce the expression of different proteins and soluble factors with a wide range of applications, such as growth factors, cytokines, chemokines, transcription factors, enzymes and microRNAs. Distinct strategies have been applied to induce genetic modifications with the goal to enhance the potential of MCSs. This review aims to contribute to the update of the different genetically engineered tools employed for MSCs modification, as well as the factors investigated in different fields in which genetically engineered MSCs have been tested.

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Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors

Cited by 16 publications

References 58 publications

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

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

Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

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