Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

Sullivan, Catherine; Barry, Frank; Ritter, Thomas; O’Flatharta, Cathal; Howard, Linda; Shaw, Georgina; Anegón, Ignacio; Murphy, Mary

doi:10.1089/scd.2013.0248

Cited by 28 publications

(18 citation statements)

References 52 publications

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“…However, various studies report beneficial effects of MSCs in CIA mice323334353637. The use of various cell strains and differences in the infused cell number or the administration route make it difficult to compare and interpret the inconsistent results of previous studies38.…”

Section: Discussionmentioning

confidence: 99%

Etanercept-Synthesising Mesenchymal Stem Cells Efficiently Ameliorate Collagen-Induced Arthritis

Park

Rim

Jung

et al. 2017

Sci Rep

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Mesenchymal stem cells (MSCs) have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and clinical treatments. These beneficial effects, however, are sometimes inconsistent and unpredictable. For wider and proper application, scientists sought to improve MSC functions by engineering. We aimed to invent a novel method to produce synthetic biological drugs from engineered MSCs. We investigated the anti-arthritic effect of engineered MSCs in a collagen-induced arthritis (CIA) model. Biologics such as etanercept are the most successful drugs used in anti-cytokine therapy. Biologics are made of protein components, and thus can be theoretically produced from cells including MSCs. MSCs were transfected with recombinant minicircles encoding etanercept (trade name, Enbrel), which is a tumour necrosis factor α blocker currently used to treat rheumatoid arthritis. We confirmed minicircle expression in MSCs in vitro based on GFP. Etanercept production was verified from the conditioned media. We confirmed that self-reproduced etanercept was biologically active in vitro. Arthritis subsided more efficiently in CIA mice injected with mcTNFR2MSCs than in those injected with conventional MSCs or etanercept only. Although this novel strategy is in a very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics and engineering MSCs.

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Section: Discussionmentioning

confidence: 99%

Etanercept-Synthesising Mesenchymal Stem Cells Efficiently Ameliorate Collagen-Induced Arthritis

Park

Rim

Jung

et al. 2017

Sci Rep

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“…The US11 gene modification contributed to evasion of recognition by cytotoxic lymphocytes and extended the persistence of MSCs in the allogeneic host. In contrast to wild-type allo-MSCs, allo-MSCs expressing cytotoxic T lymphocyte associated antigen-4 (CTLA4Ig) demonstrated enhanced inhibition of T-cell responses [ 54 ]. The genetically modified MSCs delayed the onset of inflammatory arthritis and decreased the amount of damage in collagen-induced arthritis.…”

Section: Application Strategies For Allogeneic Mscsmentioning

confidence: 99%

The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy

et al. 2015

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Mesenchymal stem cells (MSCs) are ideal for cell-based therapy in various inflammatory diseases because of their immunosuppressive and tissue repair properties. Moreover, their immunosuppressive properties and low immunogenicity contribute to a reduced or weakened immune response elicited by the implantation of allogeneic MSCs compared with other cell types. Therefore, implantation of allogeneic MSCs may be a promising cell-based therapy. In this review, we first summarize the unique advantages of allogeneic MSCs for therapeutic applications. Second, we critically analyze the factors influencing their therapeutic effects, including administration routes, detection time-points, disease models, differentiation of MSCs in vivo, and timing and dosage of MSC administration. Finally, current approaches to allogeneic MSC application are discussed. In conclusion, allogeneic MSCs are a promising option because of their low immunogenicity and immunosuppressive and tissue repair capabilities. Further investigations are needed to enhance the consistency and efficacy of MSCs when used as a cell-based therapy in inflammatory diseases as well as for tissue repair.

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“…11,12 Mesenchymal stem cells injected IV accumulate in areas of inflammation, including joints, where they can then exert local antiinflammatory and immunomodulatory effects. 13 Injection of MSCs into joints with experimentally induced osteoarthritis can decrease cartilage destruction, osteophyte formation, and subchondral sclerosis and even lead to regeneration of meniscal and articular cartilage. [14][15][16][17] Improved clinical outcomes have been reported when MSCs were injected intra-articularly into the joints of animals affected by naturally occurring osteoarthritis.…”

mentioning

confidence: 99%

Effects of administration of adipose-derived stromal vascular fraction and platelet-rich plasma to dogs with osteoarthritis of the hip joints

Upchurch¹,

Renberg²,

Roush³

et al. 2016

ajvr

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OBJECTIVE To evaluate effects of simultaneous intra-articular and IV injection of autologous adipose-derived stromal vascular fraction (SVF) and platelet-rich plasma (PRP) to dogs with osteoarthritis of the hip joints. ANIMALS 22 client-owned dogs (12 placebo-treated [control] dogs and 10 treated dogs). PROCEDURES Dogs with osteoarthritis of the hip joints that caused signs of lameness or discomfort were characterized on the basis of results of orthopedic examination, goniometry, lameness score, the Canine Brief Pain Inventory (CBPI), a visual analogue scale, and results obtained by use of a pressure-sensing walkway at week 0 (baseline). Dogs received a simultaneous intraarticular and IV injection of SVF and PRP or a placebo. Dogs were examined again 4, 8, 12, and 24 weeks after injection. RESULTS CBPI scores were significantly lower for the treatment group at week 24, compared with scores for the control group. Mean visual analogue scale score for the treatment group was significantly higher at week 0 than at weeks 4, 8, or 24. Dogs with baseline peak vertical force (PVF) in the lowest 25th percentile were compared, and the treatment group had a significantly higher PVF than did the control group. After the SVF-PRP injection, fewer dogs in the treated group than in the control group had lameness confirmed during examination. CONCLUSIONS AND CLINICAL RELEVANCE For dogs with osteoarthritis of the hip joints treated with SVF and PRP, improvements in CBPI and PVF were evident at some time points, compared with results for the control group.

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Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

Cited by 28 publications

References 52 publications

Etanercept-Synthesising Mesenchymal Stem Cells Efficiently Ameliorate Collagen-Induced Arthritis

Etanercept-Synthesising Mesenchymal Stem Cells Efficiently Ameliorate Collagen-Induced Arthritis

The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy

Effects of administration of adipose-derived stromal vascular fraction and platelet-rich plasma to dogs with osteoarthritis of the hip joints

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