Progress in intra-articular therapy

Evans, Christopher H.; Kraus, Virginia B.; Setton, Lori A.

doi:10.1038/nrrheum.2013.159

Cited by 445 publications

(424 citation statements)

References 88 publications

(92 reference statements)

Supporting

Mentioning

420

Contrasting

Unclassified

Order By: Relevance

“…Recently, there are several reports regarding adipose-derived cell therapy of degenerative OA, but all of them with relatively small number of patients [14,16,[23][24][25]. In our study, we are in agreement with these studies using adipose-derived cells which are safe and clinically effective in most patients with degenerative OA.…”

Section: Discussionsupporting

confidence: 82%

Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Moster¹,

Lukác²,

Proefrock³

et al. 2017

Glob Surg

View full text Add to dashboard Cite

Objective: Stromal vascular fraction (SVF), containing high amount of stem cells and other regenerative cells, can be easily obtained from loose connective tissue that is associated with adipose tissue. Here we evaluated safety and clinical efficacy of freshly isolated autologous SVF cells in a case control prospective multi-centric non-randomized study in patients with grade 2-4 degenerative osteoarthritis. Methods:A total of 1128 patients underwent standard liposuction under local anesthesia and SVF cells were isolated and prepared for application into 1-4 large joints. A total of 1856 joints, mainly knee and hip joints, were treated with a single dose of SVF cells. 1114 patients were followed for 12.1-54.3 months (median 17.2 months) for safety and efficacy. Modified KOOS/HOOS Clinical Score was used to evaluate clinical effect and was based on pain, non-steroid analgesic usage, limping, extent of joint movement, and joint stiffness evaluation before and at 3,6 and 12 months after the treatment. Results:No serious side effects, systemic infection or cancer was associated with SVF cell therapy. Most patients gradually improved 3-12 months after the treatment. At least 75% Score improvement was noticed in 63% of patients and at least 50% Score improvement was documented in 91% of patients 12 months after SVF cell therapy. Obesity and higher grade of OA were associated with slower healing. Conclusion:Here we report a novel and promising treatment approach for patients with degenerative osteoarthritis that is safe, cost-effective, and relying only on autologous cells.

show abstract

Section: Discussionsupporting

confidence: 82%

Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Moster¹,

Lukác²,

Proefrock³

et al. 2017

Glob Surg

View full text Add to dashboard Cite

show abstract

“…Small molecules are eliminated via synovial capillaries, whereas macromolecules are cleared by the lymphatic system [12]. As mentioned, corticosteroids and hyaluronic acid preparations are the only FDA-approved IA therapeutics, however they are limited by their residence time as well [12]. Aside from the issue of drug residency time, IA injections can be painful and pose the threat of infection.…”

Section: Chapter Iii: the Need For Sustained Targeted Drug Deliverymentioning

confidence: 99%

“…However, research into the development of IA injections has primarily been unsuccessful due to the inability to retain the therapeutic within the joint [12]. Small molecules are eliminated via synovial capillaries, whereas macromolecules are cleared by the lymphatic system [12]. As mentioned, corticosteroids and hyaluronic acid preparations are the only FDA-approved IA therapeutics, however they are limited by their residence time as well [12].…”

Section: Chapter Iii: the Need For Sustained Targeted Drug Deliverymentioning

confidence: 99%

“…Targeted intraarticular (IA) injections provide several benefits over systemic delivery such as increased bioavailability, reduced systemic exposure, fewer adverse events and lower drug loading which leads to lower drug costs [12]. However, research into the development of IA injections has primarily been unsuccessful due to the inability to retain the therapeutic within the joint [12].…”

Section: Chapter Iii: the Need For Sustained Targeted Drug Deliverymentioning

confidence: 99%

“…Currently, IA injections of high dose corticosteroids are used clinically for suppression of pain and inflammation only, but they suffer with the same problem of rapid clearance from the joint causing local and systemic toxicity [12]. Injections of hyaluronic acid (HA), a lubricating component of synovial fluid, are also available but only provide temporary pain relief [7].…”

Section: Targeted Drug Deliverymentioning

confidence: 99%

See 2 more Smart Citations

Development of in vitro joint tissue co-culture models for evaluating transport and biological crosstalk

Mehta¹

View full text Add to dashboard Cite

Osteoarthritis (OA) affects the entire joint including tissues like synovium, cartilage, meniscus and bone. Abnormal mechanical stresses (from injury or aging) produce elevated levels of inflammatory cytokines that degrade joint tissues and cause excessive neovascularization and angiogenesis. It is critical to develop effective early interventions that target both synovium, the primary initiator and source of inflammation mediators, as well as tissues like cartilage, that are at risk of irreversible proteolytic degradation.Currently employed in vitro models, however, mostly use cartilage monocultures. Here we develop a co-culture model containing cartilage, synovium and meniscus to investigate biological and transport crosstalk between multiple joint tissues. Our data showed that co-culturing cartilage with synovium in the presence of inflammatory cytokine IL-1α, resulted in significantly higher chondrocyte death and reduced cell metabolism. Surprisingly, presence of synovium in co-culture helped significantly reduce chondrocyte nitrite production, suggesting release of anti-inflammatory factor by the synovium upon cytokine challenge. Presence of meniscus in co-culture did not present as significant of an effect as synovium did. However, culturing three tissues together increased cell death in cartilage by 3 weeks. These results confirm that significant biological crosstalk exists between various tissues. Thus co-culture systems should be preferred over monocultures to model the multiple complex pathways underlying OA.It is widely accepted that OA is a disease of the entire joint and that no single compound will be sufficient to treat every aspect of OA, thus requiring a combination of therapeutics. We therefore, investigated the role of receptor antagonist IL-1Ra, growth factor IGF-1 and chondrocyte differentiator Kartogenin (KGN) in suppressing IL-1α induced catabolic activity using monoculture or co-culture models. Drugs were introduced in either a single (mimicking one-time intraarticular injection) or continuous (mimicking multiple injections) dose regimen. Our results showed that single drug-dose was insufficient and that continuous dose, which helped maintain constant drug concentration over the entire culture period, is necessary to elicit an effective therapeutic response. This highlights the need for developing sustained and targeted drug-delivery systems for OA treatment. Future work will focus on designing strategies for co-targeting multiple tissues with multiple drugs to provide a combination OA therapy.iii ACKNOWLEDGEMENTS

show abstract

Mechanically Activated Microcapsules for “On‐Demand” Drug Delivery in Dynamically Loaded Musculoskeletal Tissues

Mohanraj

Duan

Peredo

et al. 2019

Adv Funct Materials

View full text Add to dashboard Cite

Delivery of biofactors in a precise and controlled fashion remains a clinical challenge. Stimuli‐responsive delivery systems can facilitate “on‐demand” release of therapeutics in response to a variety of physiologic triggering mechanisms (e.g., pH, temperature). However, few systems to date have taken advantage of mechanical inputs from the microenvironment to initiate drug release. Here, mechanically activated microcapsules (MAMCs) are designed to deliver therapeutics in response to the mechanically loaded environment of regenerating musculoskeletal tissues, with the ultimate goal of furthering tissue repair. To establish a suite of microcapsules with different thresholds for mechanoactivation, MAMC physical dimensions and composition are first manipulated, and their mechano‐response under both direct 2D compression and in 3D matrices mimicking the extracellular matrix properties and dynamic loading environment of regenerating tissue, is evaluated. To demonstrate the feasibility of this delivery system, an engineered cartilage model is used to test the efficacy of mechanically instigated release of transforming growth factor‐β3 on the chondrogenesis of mesenchymal stem cells. These data establish a novel platform by which to tune the release of therapeutics and/or regenerative factors based on the physiologic mechanical loading environment and will find widespread application in the repair and regeneration of musculoskeletal tissues.

show abstract

Progress in intra-articular therapy

Cited by 445 publications

References 88 publications

Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Development of in vitro joint tissue co-culture models for evaluating transport and biological crosstalk

Mechanically Activated Microcapsules for “On‐Demand” Drug Delivery in Dynamically Loaded Musculoskeletal Tissues

Contact Info

Product

Resources

About