Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

Sanjurjo‐Rodríguez, Clara; Altaie, Ala; Mastbergen, S.C.; Baboolal, Thomas G.; Welting, Tim J. M.; Lafeber, Floris P. J. G.; Pandit, Hemant; McGonagle, Dennis; Jones, Elena

doi:10.3389/fbioe.2020.579751

Cited by 20 publications

(22 citation statements)

References 97 publications

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“… 49 Recently, it was shown that unloading of the joint by KJD resulted in a significant increase in synovial fluid MSC (SF-MSC) colony size and density. 50 Furthermore, after 3 weeks of KJD treatment many transcriptional changes were found in these SF-MSC compared to baseline. These changes included a sustained upregulation of ACAN and a significant increase of the MSC chondrogenic commitment markers gremlin 1, and growth differentiation factor 5 ( GDF5 ), markers associated with cartilage homeostasis and OA, among others.…”

Section: Discussionmentioning

confidence: 92%

“…These changes included a sustained upregulation of aCaN and a significant increase of the MSC chondrogenic commitment markers gremlin 1, and growth differentiation factor 5 (GdF5), markers associated with cartilage homeostasis and OA, among others. [50][51][52] In addition, the joint environment during KJD is changed, favoring attachment of MSC. 21 Another proposed mechanism is the effect of the periarticular bone turnover on the cartilage, as a decrease in subchondral bone sclerosis has been reported in humans and rats after KJD, which was directly associated with the reported clinical improvement.…”

Section: Discussionmentioning

confidence: 99%

“…These changes included a sustained upregulation of ACAN and a significant increase of the MSC chondrogenic commitment markers gremlin 1, and growth differentiation factor 5 ( GDF5 ), markers associated with cartilage homeostasis and OA, among others. 50 - 52 In addition, the joint environment during KJD is changed, favoring attachment of MSC. 21 …”

Section: Discussionmentioning

confidence: 99%

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Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

et al. 2021

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Objective Joint distraction triggers intrinsic cartilage repair in animal models of osteoarthritis (OA), corroborating observations in human OA patients treated with joint distraction. The present study explores the still largely elusive mechanism initiating this repair process. Design Unilateral OA was induced in the knee joint of 8 dogs using the groove model; the contralateral joint served as a control. After 10 weeks, 4 animals received joint distraction, the other 4 serving as OA controls. Halfway the distraction period (after 4 weeks of a standard 8-week distraction treatment), all animals were euthanized, and joint tissues were collected. A targeted quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed of commonly involved processes including matrix catabolism/anabolism, inflammation, and known signaling pathways in OA. In addition, cartilage changes were determined on tissue sections using the canine OARSI (Osteoarthritis Research Society International) histopathology score and collagen type II (COL2A1) immunostaining. Results Midway distraction, the distracted OA joint showed an upregulation of proteolytic genes, for example, ADAMTS5, MMP9, MMP13, compared to OA alone and the healthy joints, which correlated with an increased OARSI score. Additionally, genes of the transforming growth factor (TGF)-β and Notch pathway, and markers associated with progenitor cells were increased. Conclusions Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

et al. 2021

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“…Gene expression was measured using standard TaqMan assays (Thermo Fisher Scientific) and the 48 3 48 integrated fluidic circuit with the recommended reagents (Fluidigm), as previously described. 46 The integrated fluidic circuit was then run on the BioMark real-time polymerase chain reaction system using a GE 48 3 48 Standard Version 1 polymerase chain reaction thermal protocol, and data were analyzed using BioMark Gene Expression Data software and normalized to the housekeeping gene hypoxanthine phosphoribosyltransferase 1.…”

Section: Preparation Of Autologous and Allogenic Pcmentioning

confidence: 99%

Device-Based Enrichment of Knee Joint Synovial Cells to Drive MSC Chondrogenesis Without Prior Culture Expansion In Vitro: A Step Closer to 1-Stage Orthopaedic Procedures

et al. 2021

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Background: Synovial fluid (SF) mesenchymal stem cells (MSCs) are derived from the synovial membrane and have cartilage repair potential. Their current use in clinical practice is largely exploratory. As their numbers tend to be small, therapeutic procedures using MSCs typically require culture expansion. Previous reports indicate that the stem cell–mobilizing device (STEM device) intraoperatively increases SF-MSCs. Purpose: This study evaluated the chondrogenic potential of non–culture expanded synovium-mobilized MSCs and SF-microfragments obtained after enrichment using the STEM device and ascertained if device-mediated synovial membrane manipulation facilitated ongoing MSC release. Study Design: Controlled laboratory study. Methods: Two samples of aspiration fluid were collected intraoperatively before and after STEM device utilization from patients (n = 16) undergoing diagnostic or therapeutic knee arthroscopy. Human knee synovium (n = 5) was collected during total knee replacement, and a suspended culture was performed to assess the effect of the STEM device on ongoing MSC release. Colony forming unit–fibroblastic assays were used to determine the number of MSCs. Additionally, cytometric characterization of stromal and immune cells and chondrogenesis differentiation assay were performed without culture expansion. Filtered platelet concentrates were prepared using the HemaTrate system. Results: After STEM device use, a significant increase was evident in SF-MSCs ( P = .03) and synovial fluid–resident synovial tissue microfragments ( P = .03). In vitro–suspended synovium released significantly more MSCs following STEM device use than nonstimulated synovium ( P = .01). The STEM device–released total cellular fraction produced greater in vitro chondrogenesis with significantly more glycosaminoglycans (GAGs; P < .0001) when compared with non–STEM device synovial fluid material. Nonexpanded SF-MSCs and SF-microfragments combined with autologous filtered platelet concentrate produced significantly more GAGs than the complete chondrogenic media ( P < .0001). The STEM device–mobilized cells contained more M2 macrophage cells and fewer M1 cells. Conclusion: Non–culture expanded SF-MSCs and SF-microfragments had the potential to undergo chondrogenesis without culture expansion, which can be augmented using the STEM device with increased MSC release from manipulated synovium for several days. Although preliminary, these findings offer proof of concept toward manipulation of the knee joint environment to facilitate endogenous repair responses. Clinical Relevance: Although numbers were small, this study highlights 3 factors relevant to 1-stage joint repair using the STEM device: increased SF-MSCs and SF-microfragments and prolonged synovial release of MSCs. Joint repair strategies involving endogenous MSCs for cartilage repair without the need for culture expansion in a 1-stage procedure may be possible.

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“…Their characteristics like self renewably, anti-in ammatory and immunomodulatory effects have made them as a promising option for treatment of diseases [6]. Moreover, MSCs, multipotent stromal cells, can differentiate into multiple lineages of cells including chondrocytes (cartilage) and osteoblasts (bone) whereby limitations of poor intrinsic regeneration of cartilage tissue lesion due to the disability of resident articular chondrocytes to secrete a matrix could be reparated [7]. Derived-MSCs of various sources such as amniotic uid, bone marrow, umbilical cord, adipose tissue, synovial uid, have been evaluated in a lot of experimental studies about different diseases.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Osteoarthritis Progression via a Combination of Intra-articular Injection of Synovial Membrane-derived MSCs (SMMSCs), Platelet Rich Plasma (PRP) and Conditioned Medium (Secretome)

Nabavizadeh

Talaei‐Khozani

Zarei

et al. 2021

Preprint

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Introduction: Osteoarthritis (OA) as a progressive destructive disease of articular cartilage is the most common joint disease characterized by reduction of joint cartilage thickness, demolition of cartilage surface and new bone formation. To overcome these problems, the purpose of the current research was to evaluate and compare the in vivo effects of Synovial membrane-derived MSCs (SMMSCs), platelet rich plasma (PRP) and conditioned medium (secretome) on collagenase II-induced rat knee osteoarthritis (KOA) remedy. Methods: For the first step, SMMSCs were isolated and characterized. Also, secretome was collected from SMMSCs culture. Furthermore, PRP was collect from the rat heart venous blood. Second, two injection of collagenase II with an interval of 3 days was performed in the knee intra- articular space to induce osteoarthritis. Two weeks later, animals were randomly divided into 6 groups. Control group without treatment, positive group: taken an intra-articular Hyalgan injection (0.1 cc), treatment groups taken an intra-articular injection of; treatment 1: SMMSCs (5 × 106), treatment 2: SMMSCs (5 × 106) + secretome (50 µl), treatment 3: SMMSCs (5 × 106) + PRP (50 µl), and treatment 4: SMMSCs (5 × 106) + secretome (50 µl) + PRP (50 µl). Three months later, rats were sacrificed and the following assessments were executed: radiography, histopathology, and immunohistochemistry. Results: Our findings represented that a combination of the SMMSCs with PRP and secretome had a considerable effect on GAGs and collagen II contents, articular cartilage preservation, compared with other groups. In addition, combination of the SMMSCs with PRP and secretome showed the lowest expression of mmp3, while SOX9 had the highest expression in comparision with other groups. Also, SMMSCs -injected groups demonstrated better results compared with positive and control groups. Conclusions: Injection a combination of the SMMSCs with PRP and secretome resulted in better efficacy in terms of joint space width, articular cartilage surface continuity and integrity, sub chondral bone and ECM constituents such as collagen II. Indeed, transplantation of this combination could be considered as a promising therapy for patients with KOA.

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Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

Cited by 20 publications

References 97 publications

Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

Device-Based Enrichment of Knee Joint Synovial Cells to Drive MSC Chondrogenesis Without Prior Culture Expansion In Vitro: A Step Closer to 1-Stage Orthopaedic Procedures

Attenuation of Osteoarthritis Progression via a Combination of Intra-articular Injection of Synovial Membrane-derived MSCs (SMMSCs), Platelet Rich Plasma (PRP) and Conditioned Medium (Secretome)

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