Lack of anti-inflammatory and anti-catabolic effects on basal inflamed osteoarthritic chondrocytes or synoviocytes by adipose stem cell-conditioned medium.

Published on Nov 1, 2015in Osteoarthritis and Cartilage4.793
· DOI :10.1016/J.JOCA.2015.03.025
Cristina Manferdini19
Estimated H-index: 19
Marie Maumus19
Estimated H-index: 19
(University of Montpellier)
+ 6 AuthorsGina Lisignoli37
Estimated H-index: 37
Summary Objective To define whether good manufacturing practice (GMP)-clinical grade adipose stem cell (ASC)-derived conditioned medium (CM) is as effective as GMP-ASC in modulating inflammatory and catabolic factors released by both osteoarthritis (OA) chondrocytes or synoviocytes. Methods OA chondrocytes and synoviocytes were treated with ASC-CM or co-cultured with ASC. Inflammatory factors (IL6, CXCL1/GROα,CXCL8/IL8, CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES) and proteinases, such as metalloproteinase (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS4, ADAMTS5) and their tissue metalloproteinase inhibitors (TIMP1, TIMP3) were evaluated by qRT-PCR or immunoassays. The involvement of prostaglandin E2 (PGE2) was also analyzed. Results Most ASC-CM ratios tested did not decrease IL6, CCL2/MCP-1, CCL3/MIP1-α, CCL5/RANTES on basal inflamed chondrocytes or synoviocytes in contrast to what we found using ASC in co-culture. CXCL8/IL8 and CXCL1/GROα were not decreased by ASC-CM on synoviocytes but were only partially reduced on chondrocytes. Moreover, ASC-CM was less efficient both on basal inflamed OA chondrocytes and synoviocytes in reducing proteinases, such as MMP13, ADAMTS4, ADAMTS5 and increasing TIMP1 and TIMP3 compared to ASC in co-culture. The different ratios of ASC-CM contain lower amounts of PGE2 which were not sufficient to reduce inflammatory factors. Conclusions These data show that ASC-CM has a limited ability to decrease inflammatory and proteinases factors produced by OA chondrocytes or synoviocytes. ASC-CM is not sufficient to recapitulate the beneficial effect demonstrated using ASC in co-culture with inflamed OA chondrocytes and synoviocytes and shows that their use in clinical trials is fundamental to counteract OA progression.
📖 Papers frequently viewed together
131 Citations
52 Citations
#1A.I. Tsuchida (UU: Utrecht University)H-Index: 9
#2M. Beekhuizen (UU: Utrecht University)H-Index: 6
Last. Laura B. Creemers (UU: Utrecht University)H-Index: 54
view all 8 authors...
Introduction This study aimed to evaluate whether profiles of several soluble mediators in synovial fluid and cartilage tissue are pathology-dependent and how their production is related to in vitro tissue formation by chondrocytes from diseased and healthy tissue. Methods Samples were obtained from donors without joint pathology (n = 39), with focal defects (n = 65) and osteoarthritis (n = 61). A multiplex bead assay (Luminex) was performed measuring up to 21 cytokines: Interleukin (IL)-1α, IL-...
91 CitationsSource
#1Julia Platas (University of Valencia)H-Index: 3
#2Maria Isabel Guillén (University of Valencia)H-Index: 19
Last. María José Alcaraz (University of Valencia)H-Index: 45
view all 6 authors...
Osteoarthritis (OA) is the most frequent joint disorder and an important cause of disability. Recent studies have shown the potential of adipose-tissue-derived mesenchymal stem cells (AD-MSC) for cartilage repair. We have investigated whether conditioned medium from AD-MSC (CM) may regulate in OA chondrocytes a number of key mediators involved in cartilage degeneration. CM enhanced type II collagen expression in OA chondrocytes while decreasing matrix metalloproteinase (MMP) activity in cell sup...
41 CitationsSource
#1Marie Maumus (French Institute of Health and Medical Research)H-Index: 19
#2Christian Jorgensen (University of Montpellier)H-Index: 92
Last. Danièle Noël (University of Montpellier)H-Index: 67
view all 3 authors...
Over the last decades, mesenchymal stem cells (MSCs) have been extensively studied with regard to their potential applications in regenerative medicine. In rheumatic diseases, MSC-based therapy is the subject of great expectations for patients who are refractory to proposed treatments such as rheumatoid arthritis (RA), or display degenerative injuries without possible curative treatment, such as osteoarthritis (OA). The therapeutic potential of MSCs has been demonstrated in several pre-clinical ...
151 CitationsSource
#1Matthew B. MurphyH-Index: 14
#2Kathryn MoncivaisH-Index: 4
Last. Arnold I. Caplan (Case Western Reserve University)H-Index: 129
view all 3 authors...
Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant ...
663 CitationsSource
#1Amy M. DiMarino (Case Western Reserve University)H-Index: 2
#2Arnold I. Caplan (Case Western Reserve University)H-Index: 129
Last. Tracey L. Bonfield (Case Western Reserve University)H-Index: 34
view all 3 authors...
The advent of mesenchymal stem cell (MSC) based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the pr...
272 CitationsSource
#1Marie Maumus (French Institute of Health and Medical Research)H-Index: 19
#2Cristina ManferdiniH-Index: 19
Last. Danièle Noël (University of Montpellier)H-Index: 67
view all 11 authors...
Abstract Our work aimed at evaluating the role of adipose stem cells (ASC) on chondrocytes from osteoarthritic (OA) patients and identifying the mediators involved. We used primary chondrocytes, ASCs from different sources and bone marrow mesenchymal stromal cells (MSC) from OA donors. ASCs or MSCs were co-cultured with chondrocytes in a minimal medium and using cell culture inserts. Under these conditions, ASCs did not affect the proliferation of chondrocytes but significantly decreased camptot...
90 CitationsSource
#1Brian O. Diekman (Duke University)H-Index: 16
#2Chia-Lung Wu (Duke University)H-Index: 13
Last. Farshid Guilak (Duke University)H-Index: 120
view all 8 authors...
Joint injury dramatically enhances the onset of osteoarthritis (OA) and is responsible for an estimated 12% of OA. Posttraumatic arthritis (PTA) is especially common after intra-articular fracture, and no disease- modifying therapies are currently available. We hypothesized that the delivery of mesenchymal stem cells (MSCs) would prevent PTA by altering the balance of inflammation and regeneration after fracture of the mouse knee. Additionally, we examined the hypothesis that MSCs from the MRL/M...
90 CitationsSource
#1Enrico Ragni (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)H-Index: 23
#2Tiziana Montemurro (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)H-Index: 16
Last. Lorenza Lazzari (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)H-Index: 33
view all 8 authors...
Abstract Human mesenchymal stem cells (MSCs) are multipotent cells offering valuable hopes for the treatment of degenerative diseases. MSCs can be found among differentiated cells in many tissues and organs but, unfortunately, their phenotypic similarity hinders a robust cell characterization and discrimination from diverse tissue harvests. MicroRNAs (miRNAs) are crucial managers of gene expression with intriguing and still poorly known roles in stem cell maintenance and differentiation. To iden...
40 CitationsSource
#1Sara M. Melief (LUMC: Leiden University Medical Center)H-Index: 7
#2Jaap Jan Zwaginga (LUMC: Leiden University Medical Center)H-Index: 42
Last. Helene Roelofs (LUMC: Leiden University Medical Center)H-Index: 33
view all 4 authors...
Adipose tissue-derived multipotent stromal cells (AT-MSCs) are studied as an alternative to bone marrow-derived multipotent stromal cells (BM-MSCs) for immunomodulatory treatment. In this study, we systematically compared the immunomodulatory capacities of BM-MSCs and AT-MSCs derived from age-matched donors. We found that BM-MSCs and AT-MSCs share a similar immunophenotype and capacity for in vitro multilineage differentiation. BM-MSCs and AT-MSCs showed comparable immunomodulatory effects as th...
219 CitationsSource
#1Cristina ManferdiniH-Index: 19
#2Marie Maumus (University of Montpellier)H-Index: 19
Last. Gina LisignoliH-Index: 37
view all 12 authors...
Objective To examine the effect of different sources of Good Manufacturing Practice clinical grade adipose-derived mesenchymal stem cells (AD-MSCs) on inflammatory factors in osteoarthritic (OA) chondrocytes and synoviocytes. Methods AD-MSCs from infrapatellar Hoffa fat, subcutaneous (SC) hip fat, and SC abdominal fat were cocultured in Transwells with chondrocytes or synoviocytes. Inflammatory factors (interleukin-1β [IL-1β], tumor necrosis factor α, IL-6, CXCL1/growth-related oncogene α, CXCL8...
131 CitationsSource
Cited By14
#1Wataru Katagiri (Niigata University)H-Index: 15
#2Satoshi Endo (Niigata University)H-Index: 1
Last. Tadaharu Kobayashi (Niigata University)H-Index: 16
view all 6 authors...
Abstract Condylar resorption (CR) after surgical orthognathic treatment is defined as dysfunctional remodeling of the temporomandibular joint manifested by morphological changes with decreased condylar head volume that cause occlusal and esthetic changes. Although both conservative and surgical treatment strategies have been employed for the treatment of CR, effective procedures have not been established till date. In this study, the effects of MSC-CM on CR were investigated. Bone marrow-derived...
#1C. GiannasiH-Index: 7
#1Chiara GiannasiH-Index: 2
Last. Anna T. Brini (University of Milan)H-Index: 28
view all 6 authors...
In the last years, several clinical trials have proved the safety and efficacy of adipose-derived stem/stromal cells (ASC) in contrasting osteoarthritis (OA). Since ASC act mainly through paracrine mechanisms, their secretome (conditioned medium, CM) represents a promising therapeutic alternative. ASC-CM is a complex cocktail of proteins, nucleic acids, and lipids released as soluble factors and/or conveyed into extracellular vesicles (EV). Here, we investigate its therapeutic potential in an in...
2 CitationsSource
#1Stefania NiadaH-Index: 16
#2C. GiannasiH-Index: 7
Last. Anna T. Brini (University of Milan)H-Index: 28
view all 6 authors...
Abstract Recent clinical trials show the efficacy of Adipose-derived Stromal Cells (ASCs) in contrasting the osteoarthritis scenario. Since it is quite accepted that ASCs act predominantly through a paracrine mechanism, their secretome may represent a valid therapeutic substitute. The aim of this study was to investigate the effects of ASC conditioned medium (ASC-CM) on TNFα-stimulated human primary articular chondrocytes (CHs). CHs were treated with 10 ng/ml TNFα and/or ASC-CM (1:5 recipient:do...
9 CitationsSource
#1Enrico RagniH-Index: 23
#2Paola De LucaH-Index: 11
Last. Laura de GirolamoH-Index: 23
view all 8 authors...
Mesenchymal stem cells (MSCs) are promising tools for cell-based therapies due to their homing to injury sites, where they secrete bioactive factors such as cytokines, lipids, and nucleic acids, either free or conveyed within extracellular vesicles (EVs). Depending on the local environment, MSCs’ therapeutic value may be modulated, determining their fate and cell behavior. Inflammatory signals may induce critical changes on both the phenotype and secretory portfolio. Intriguingly, in animal mode...
8 CitationsSource
: Cell-based therapies using adipose-derived mesenchymal stromal cells (ADMSCs) have shown promising results for the treatment of osteoarthritis (OA). In fact, ADMSCs are now indicated as one of the most powerful cell sources through their immunomodulatory and anti-inflammatory activities. Recently, an innovative one-step closed device was developed to obtain microfragmented adipose tissue (MF) to avoid the need for good manufacturing practices for ADMSCs expansion while maintaining their regene...
9 CitationsSource
#1Sara NavaH-Index: 16
#2Valeria SordiH-Index: 23
Last. Giulio AlessandriH-Index: 48
view all 12 authors...
Over the last few years, human microfragmented adipose tissue (MFAT), containing significant levels of mesenchymal stromal cells (MSCs) and obtained from fat lipoaspirate (LP) through a minimal manipulation in a closed system device, has been successfully used in aesthetic medicine as well as in orthopedic and general surgery. Interestingly, in orthopedic diseases, this ready-to-use adipose tissue cell derivative seems to have a prolonged time efficacy even upon a single shot injection into oste...
13 CitationsSource
#1Yu-Chun Chen (YZU: Yuan Ze University)H-Index: 7
#2Yu-Wei ChangH-Index: 1
Last. Chih-Hung Chang (YZU: Yuan Ze University)H-Index: 17
view all 6 authors...
: Osteoarthritis (OA), one of the most common joint disease, affects more than 80% of the population aged 70 or over. Mesenchymal stem cells (MSCs) show multi-potent differentiation and self-renewal capability, and, after exposure to an inflammatory environment, also exhibit immunosuppressive properties. In this study, we have used a model of lipopolysaccharide (LPS)-stimulated chondrocytes to evaluate MSC anti-inflammatory efficacy. The anti-inflammatory mechanism was tested in two cell-contain...
15 CitationsSource
#1Marjorie E. Bateman (Tulane University)H-Index: 5
#2Amy L. StrongH-Index: 19
Last. Bruce A. Bunnell (Tulane University)H-Index: 57
view all 4 authors...
: The objective of this Review is to describe the safety and efficacy of adipose stem/stromal cells (ASC) and stromal vascular fraction (SVF) in treating common diseases and the next steps in research that must occur prior to clinical use. Pubmed, Ovid Medline, Embase, Web of Science, and the Cochrane Library were searched for articles about use of SVF or ASC for disease therapy published between 2012 and 2017. One meta-analysis, 2 randomized controlled trials, and 16 case series were included, ...
55 CitationsSource
#1Claudio Pirozzi (Usach: University of Santiago, Chile)H-Index: 14
#2Vera Francisco (Usach: University of Santiago, Chile)H-Index: 9
Last. Oreste Gualillo (Usach: University of Santiago, Chile)H-Index: 63
view all 8 authors...
Background/Aims: Osteoarthritis (OA) is a joint degenerative biomechanical disorder involving immunity, metabolic alterations, inflammation, and cartilage degradation, where chondrocytes play a pivotal role. OA has not effective pharmacological treatments and new therapeutic targets are needed. Adipokines contribute to the low-grade systemic inflammation in OA. Here, we explored novel molecular mechanisms of sodium butyrate (BuNa) in modulating inflammation and chemotaxis in chondrocytes, demons...
21 CitationsSource
#1Cristina ManferdiniH-Index: 19
#2Francesca PaolellaH-Index: 8
Last. Gina LisignoliH-Index: 37
view all 10 authors...
Summary Objective To define if adipose mesenchymal stromal cell (ASC) treatment mediated switching of the pro-inflammatory profile of M1-like macrophages as a means to develop a tailored in vitro efficacy/potency test. Design We firstly performed immunohistochemical analysis of CD68, CD80 (M1-like) and CD206 (M2-like) macrophages in osteoarthritic (OA) synovial tissue. ASC were co-cultured in contact and in transwell with activated (GM-CSF + IFNγ)-M1 macrophages. We analyzed IL1β, TNFα, IL6, MIP...
47 CitationsSource