Intra‐articular injection of autologous adipose‐derived mesenchymal stem cells in the treatment of knee osteoarthritis

Spasovski, Duško; Spasovski, Vesna; Baščarević, Zvezdana; Stojiljković, Maja; Vreća, Miša; Anđelković, Marina; Pavlović, Sonja

doi:10.1002/jgm.3002

Cited by 80 publications

(83 citation statements)

References 31 publications

(49 reference statements)

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“…If non‐surgical approaches are not successful, treatment options for advanced OA are limited to partial or total knee arthroplasty, while focal chondral defects can be treated with joint preserving options, including marrow stimulation with or without augmentation, osteochondral autografts and allografts, cell‐based therapy, scaffolds, osteotomy, and meniscal transplantation . In addition to traditional OA treatments, advanced biologic options have recently been used clinically with some success including platelet‐rich plasma, adipose‐derived stem cells, bone marrow‐derived cells, allogenic mesenchymal stem cells, and autologous protein solution (APS) . Furthermore, a pilot clinical study evaluating the safety profile of ASA was recently published by Vines et al confirming the safety of ASA for injection and suggesting a clinical benefit for up to 1 year based on patient‐reported outcomes.…”

Section: Discussionmentioning

confidence: 99%

Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis

Kimmerling

Gomoll

Farr

et al. 2019

Journal Orthopaedic Research

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Osteoarthritis (OA) affects over 301 million adults worldwide. Inflammation is a recognized component of the OA process; two potent pro-inflammatory cytokines involved in OA are interleukin-1β and tumor necrosis factor-α. Placental-derived tissues and fluids are known to contain anti-inflammatory and immunomodulatory cytokines and growth factors. The objective of this study was to evaluate the anti-inflammatory effects of amniotic suspension allograft (ASA) in an in vivo model of OA; we evaluated pain, function, and cytokine levels following ASA treatment in the rat monosodium iodoacetate (MIA) OA pain model. Rats were injected with 2 mg of MIA, which causes pain, cartilage degeneration, and inflammation, followed by treatment with saline, triamcinolone (positive control), or ASA 7 days following disease induction with MIA. Behavioral assays, including gait analysis, mechanical pain threshold, incapacitance, and swelling were evaluated, along with histology and serum and synovial fluid biomarkers. Treatment with ASA resulted in significant improvements in pain threshold, while weight bearing aversion and swelling were significantly decreased. There were no differences between groups in total joint score after histological grading. Serum biomarkers did not show differences, indicating a lack of systemic response; however, synovial fluid levels of IL-10 were significantly increased in animals treated with ASA. ASA treatment significantly reduced pain, weight-bearing aversion and swelling. This study provides mechanistic data regarding potential therapeutic effects of ASA in OA and preliminary evidence of the anti-inflammatory nature of ASA.

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Section: Discussionmentioning

confidence: 99%

Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis

Kimmerling

Gomoll

Farr

et al. 2019

Journal Orthopaedic Research

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“…These strategies lead to improved volume retention lacking cysts and necrotic tissue (Li et al, 2017). Similar to the described approach, the enrichment of the SVF together with matrix and microvasculature may contribute substantially to the superior quality of these grafting materials (Feng et al, 2015;van Dongen et al, 2016). In comparison to the standard-SVF, the microtissue-SVF demonstrated a highly elevated potential to form tube-like structures in vitro, indicative of its angiogenic potential in vivo.…”

Section: Fig 4 Flow Cytometry Analysis Of Svf Subpopulationsmentioning

confidence: 93%

“…Enhanced wound healing properties are demonstrated with a fat graft termed ECM/SVF-gel, secreting high MCP-1 and angiogenic factors (Liu et al, 2011;Sun et al, 2017), suggesting wound healing as another field of application for the microtissue-SVF. A high angiogenic potential particularity predestines the material for regeneration of large areas of vascularised tissues, such as large skin defects and bone replacement (Jacobsen et al, 2008).…”

Section: Fig 4 Flow Cytometry Analysis Of Svf Subpopulationsmentioning

confidence: 99%

“…Since the microtissue-SVF further revealed a high chondrogenic differentiation potential (collagen type II and aggrecan expression and matrix deposition), it fulfils the requirements for application in osteoarthritis (OA). Previous approaches already show a therapeutic effect of either ASCs or SVF after intraarticular injection into the osteoarthritic joints (Jo et al, 2014;Pak et al, 2016a;Spasovski et al, 2017). The microtissue-SVF could be suitable to further improve the regenerative efficiency of SVFbased methods by direct application of the matrixentrapped cells to smoothen the rough surface and provide a temporal scaffold.…”

Section: Fig 4 Flow Cytometry Analysis Of Svf Subpopulationsmentioning

confidence: 99%

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Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction

Nürnberger¹,

Lindner²,

Maier³

et al. 2019

eCM

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The prerequisite for a successful clinical use of autologous adipose-tissue-derived cells is the highest possible regenerative potential of the applied cell population, the stromal vascular fraction (SVF). Current isolation methods depend on high enzyme concentration, lysis buffer, long incubation steps and mechanical stress, resulting in single cell dissociation. The aim of the study was to limit cell manipulation and obtain a derivative comprising therapeutic cells (microtissue-SVF) without dissociation from their natural extracellular matrix, by employing a gentle good manufacturing practice (GMP)-grade isolation. The microtissue-SVF yielded larger numbers of viable cells as compared to the improved standard-SVF, both with low enzyme concentration and minimal dead cell content. It comprised stromal tissue compounds (collagen, glycosaminoglycans, fibroblasts), capillaries and vessel structures (CD31 + , smooth muscle actin + ). A broad range of cell types was identified by surface-marker characterisation, including mesenchymal, haematopoietic, pericytic, blood and lymphatic vascular and epithelial cells. Subpopulations such as supra-adventitial adipose-derived stromal/stem cells and endothelial progenitor cells were significantly more abundant in the microtissue-SVF, corroborated by significantly higher potency for angiogenic tube-like structure formation in vitro. The microtissue-SVF showed the characteristic phenotype and tri-lineage mesenchymal differentiation potential in vitro and an immunomodulatory and pro-angiogenic secretome. In vivo implantation of the microtissue-SVF combined with fat demonstrated successful graft integration in nude mice. The present study demonstrated a fast and gentle isolation by minor manipulation of liposuction material, achieving a therapeutically relevant cell population with high vascularisation potential and immunomodulatory properties still embedded in a fraction of its original matrix.

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“…In some cases there are reported improvements to cartilage morphology . Although clinical trials of BM‐MSCs have reported efficacy at higher doses ranging from 25 × 10 6 cells and 40 × 10 6 cells , efficacy has been reported with lower doses of adipose tissue‐derived MSC suggestive of tissue‐specific differences in dosing efficacy.…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation

Chahal

Gómez‐Aristizábal

Shestopaloff

et al. 2019

Stem Cells Translational Medicine

154

171

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Patients with late‐stage Kellgren‐Lawrence knee osteoarthritis received a single intra‐articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM‐MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient‐reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast‐enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM‐MSCs were characterized by a panel of anti‐inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro‐inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM‐MSC anti‐inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM‐MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM‐MSC dosing and BM‐MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757

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Intra‐articular injection of autologous adipose‐derived mesenchymal stem cells in the treatment of knee osteoarthritis

Abstract: The results obtained in the present study provide good basis for prospective randomized controlled clinical trials with respect to the use of AD-MSCs in the treatment of osteoarthritis.

Cited by 80 publications

References 31 publications

Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis

Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis

Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction

Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation

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