Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis

Bastos, Ricardo; Mathias, Marcelo Bezerra de; Andrade, Renato; Bastos, Raquel Littério de; Balduino, Alex; Schott, Vinicius; Rodeo, Scott A.; Espregueira-Mendes, João

doi:10.1007/s00167-018-4883-9

Cited by 85 publications

(83 citation statements)

References 44 publications

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“…Data from our 12‐patient autologous BM‐MSC trial show statistically significant improvements in KOOS pain, symptoms, and QOL scores as well as WOMAC stiffness from baseline to 12‐month follow‐up. Our findings support that BM‐MSCs induce analgesic effects and functional improvements, similar to other trials .…”

Section: Discussionsupporting

confidence: 91%

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

173

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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Section: Discussionsupporting

confidence: 91%

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

173

171

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“…Recent evidence indicated that MSCs serve as responder cells following transplantation, licensed by the host in order to secrete repair molecules. Moreover, after intra-articular delivery, low levels of MSC engraftment (typically 3% or less) accompanied by rapid clearance of the bulk population were observed [31][32][33]. In this study, xenografted human WJMSCs were delivered into rat knees with OA.…”

Section: Discussionmentioning

confidence: 94%

“…Additional peripheral blood stem cell injection resulted in better histologic and MRI evaluations [39]. Dr. Bastos reported that MSCs in combination with platelet-rich plasma (PRP) significantly improved the pain, function, daily living activities, and quality of life subscales in nine patients with symptomatic knee osteoarthritis [31], but the synergistic mechanism remains unclear. Some studies elaborated that oxygen tension, growth factor composition, and mechanical properties may serve to directly influence paracrine activity and regulate certain signaling pathways involved in chondrogenesis, chondral apoptosis, and osteogenesis [36][37][38]40,41].…”

Section: Discussionmentioning

confidence: 99%

Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis

Hsu

Cheng

Wang

et al. 2020

IJMS

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Extracorporeal shockwave therapy (ESWT) and mesenchymal stem cells (MSCs) have been reported to have chondroprotective effects in knee osteoarthritis (OA). Here, we examined whether autologous adipose-derived mesenchymal stem cells (ADMSCs) and human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) increased the efficacy of ESWT in knee OA, and compared the efficacy of the two. The treatment groups exhibited significant improvement of knee OA according to pathological analysis, micro-computed tomography (CT), and immunohistochemistry (IHC) staining. The ADMSCs and ESWT+ADMSCs groups exhibited increased trabecular thickness and bone volume as compared with the ESWT, WJMSCs, and ESWT+WJMSCs groups individually. According to the results of IHC staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) activity and caspase-3 were significantly reduced in the ADMSCs and ESWT+ADMSCs groups as compared with the WJMSCs and ESWT+WJMSC groups. In mechanistic factor analysis, the synergistic effect of ESWT+ADMSCs was observed as being greater than the efficacies of other treatments in terms of expressions of transforming growth factor (TGF)-β, runt-related transcription factor (RUNX)-2 and sex determining region Y-box (SOX)-9. The type II collagen was expressed at a higher level in the WJMSCs group than in the others. Furthermore, ESWT+ADMSCs reduced the expression of platelet-derived growth factor (PDGF)-BB and increased the expression of bone morphogenetic protein (BMP)-4. Therefore, we demonstrated that ESWT+ADMSCs had a synergistic effect greater than that of ESWT+WJMSCs for the treatment of early knee OA.

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“…Some of its properties, such as its low immunogenicity, easy accessibility and role as an activator of the mechanism of hyaline cartilage production (related with the TGF-β1/SMAD signaling pathway) de ne the PRP as a potentially attractive coadjuvant [35,36]. Reporting a clinical study with 18 patients, Bastos et al concluded that the use of PRP as co-adjuvant together with 40 million BM-MSCs did not provide additional bene ts over the use of BM-MSCs alone [37]. The same group, in a recent clinical trial, compared the use of 40 million BM-MSCs (n=14) with and without PRP (n=16) and corticosteroids (n=17) as standard control treatment, no differences were observed in the use of adjuvant therapy with PRP in the treatment of these patients [17].…”

Section: Discussionmentioning

confidence: 99%

Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

Lamo-Espinosa

Blanco

Sánchez

et al. 2020

Preprint

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Background: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial.Methods: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100x106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.Results: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage.Conclusions: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23

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Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis

Abstract: Prospective cohort study, Level II.

Cited by 85 publications

References 44 publications

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

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

Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis

Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

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