Adipose‐Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing

Polly, Shelley S; Nichols, Anne E. C.; Donnini, Elle; Inman, Daniel J.; Scott, Timothy J.; Apple, Stephanie M; Werre, Stephen R.; Dahlgren, Linda A.

doi:10.1002/jor.24307

Cited by 32 publications

(25 citation statements)

References 50 publications

(136 reference statements)

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“…The discrepancy between the results described in literature and those reported in the present study is probably due to the different sources of TCs and to the inflammatory protocol. Since adipose-derived MSCs are known to produce trophic mediator-specific for TCs [49], a slight reduction of SCX expression was observed when TCs were cocultured with μ FAT in basal conditions, and a downregulation of this marker have been already reported by other authors after TCs-MSCs coculture [34]. These observations suggest that μ FAT (or MSCs) trophic action on TCs may be independent of SCX upregulation.…”

Section: Discussionmentioning

confidence: 57%

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Viganò

Lugano

Orfei

et al. 2019

Stem Cells International

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Background Mesenchymal stem cells (MSCs) emerged as a promising therapy for tendon pathologies. Microfragmented adipose tissue (μFAT) represents a convenient autologous product for the application of MSC-based therapies in the clinical setting. In the present study, the ability of μFAT to counteract inflammatory processes induced by IL-1β on human tendon cells (TCs) was evaluated. Methods Cell viability and proliferation were evaluated after 48 hours of transwell coculture of TCs and autologous μFAT in the presence or absence of IL-1β. Gene expression of scleraxis, collagen type I and type III, metalloproteinases-1 and -3, and cyclooxygenase-2 was evaluated by real-time RT-PCR. The content of VEGF, IL-1Ra, TNFα, and IL-6 was evaluated by ELISA. Results IL-1β-treated TCs showed augmented collagen type III, metalloproteases, and cyclooxygenase-2 expression. μFAT was able to reduce the expression of collagen type III and metalloproteases-1 in a significant manner, and at the same time, it enhanced the production of VEGF, IL-1Ra, and IL-6. Conclusions In this in vitro model of tendon cell inflammation, the paracrine action of μFAT, exerted by anti-inflammatory molecules and growth factors, was able to inhibit the expression of fibrosis and catabolic markers. Then, these results suggest that the application of μFAT may represent an effective conservative or adjuvant therapy for the treatment of tendon disorders.

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Section: Discussionmentioning

confidence: 57%

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Viganò

Lugano

Orfei

et al. 2019

Stem Cells International

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“…In contrast, expansion of ASCs in vitro may be associated with risks such as possible loss of stemness or cell transformation [29][30][31]. On the other hand, recent studies on culture systems and animal models indicated non-inferiority or even superiority of UA-ADRCs over ASCs in, for example, tendon healing [32], bone regeneration [33] and rescuing heart function after acute myocardial infarction [34] (see also [13]).…”

Section: Introductionmentioning

confidence: 99%

Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent

Winnier¹,

Valenzuela²,

Peters-Hall³

et al. 2019

PLoS ONE

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Freshly isolated, uncultured, autologous adipose derived regenerative cells (ADRCs) have emerged as a promising tool for regenerative cell therapy. The Transpose RT system (InGeneron, Inc., Houston, TX, USA) is a system for isolating ADRCs from adipose tissue, commercially available in Europe as a CE-marked medical device and under clinical evaluation in the United States. This system makes use of the proprietary, enzymatic Matrase Reagent for isolating cells. The present study addressed the question whether the use of Matrase Reagent influences cell yield, cell viability, live cell yield, biological characteristics, physiological functions or structural properties of the ADRCs in final cell suspension. Identical samples of subcutaneous adipose tissue from 12 subjects undergoing elective lipoplasty were processed either with or without the use of Matrase Reagent. Then, characteristics of the ADRCs in the respective final cell suspensions were evaluated. Compared to non-enzymatic isolation, enzymatic isolation resulted in approximately twelve times higher mean cell yield (i.e., numbers of viable cells/ml lipoaspirate) and approximately 16 times more colony forming units. Despite these differences, cells isolated from lipoaspirate both with and without the use of Matrase Reagent were independently able to differentiate into cells of all three germ layers. This indicates that biological characteristics, physiological functions or structural properties relevant for the intended use were not altered or induced using Matrase Reagent. A comprehensive literature review demonstrated that isolation of ADRCs from lipoaspirate using the Transpose RT system and the Matrase Reagent results in the highest viable cell yield among published data regarding isolation of ADRCs from lipoaspirate.

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“…Firstly, it contains a cell population at its surface that resembles those lining the synovium, being responsible for the production of HA and PRG4 in joint fluid. Secondly, the autocrine properties of adipose tissue with its resident multipotent stromal cells can serve as a source of inflammatory mediators, such as interleukins, nitric oxide, chemokines, and prostaglandins [ 56 ]. Thirdly, this multipotent cell population has been described in post-injury responses, including cellular proliferation, HA accumulation, and fibrotic remodeling, as well as having a potential for neo-vascularization [ 57 ], chondrogenesis [ 58 ], or modulation of pain responses [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican

Xue

Chen

Shen

et al. 2020

Cells

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We have examined the effect of exogenous linear chain high molecular weight hyaluronic acid (HMW HA) on endogenously synthesized hyaluronic acid (HA) and associated binding proteins in primary cultures of fibroblast-like stromal cells that were obtained by collagenase digestion of the murine peripatellar fat pad. The cultures were expanded in DMEM that was supplemented with fetal bovine serum and basic fibroblast growth factor (bFGF) then exposed to macrophage-colony-stimulating factor (MCSF) to induce macrophage properties, before activation of inflammatory pathways using E. coli lipopolysaccharide (LPS). Under all culture conditions, a significant amount of endogenously synthesized HA localized in LAMP1-positive lysosomal vesicles. However, this intracellular pool was depleted after the addition of exogenous HMW HA and was accompanied by enhanced proteolytic processing and secretion of de novo synthesized versican, much of which was associated with endosomal compartments. No changes were detected in synthesis, secretion, or proteolytic processing of aggrecan or lubricin (PRG4). The addition of HMW HA also modulated a range of LPS-affected genes in the TLR signaling and phagocytosis pathways, as well as endogenous HA metabolism genes, such as Has1, Hyal1, Hyal2, and Tmem2. However, there was no evidence for association of endogenous or exogenous HMW HA with cell surface CD44, TLR2 or TLR4 protein, suggesting that its physiochemical effects on pericelluar pH and/or ionic strength might be the primary modulators of signal transduction and vesicular trafficking by this cell type. We discuss the implications of these findings in terms of a potential in vivo effect of therapeutically applied HMW HA on the modification of osteoarthritis-related joint pathologies, such as pro-inflammatory and degradative responses of multipotent mesenchymal cells residing in the synovial membrane, the underlying adipose tissue, and the articular cartilage surface.

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Adipose‐Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing

Cited by 32 publications

References 50 publications

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent

Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican

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