Treatment of Knee Osteoarthritis With Autologous Mesenchymal Stem Cells

Orozco, Lluís; Munar, Anna; Soler, Robert; Alberca, Mercedes; Soler, Francesc; Huguet, Marina; Sentís, Joan; Sánchez, Abraham; García‐Sancho, Javier

doi:10.1097/tp.0000000000000167

Cited by 198 publications

(207 citation statements)

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“…Nevertheless, a difference could be observed between the high dose and control groups, which did exhibit comparable baseline values. This finding is consistent with MRI observations and is in agreement with previous reports that also investigated the role of cultured MSCs or MSCs embedded in scaffolds in knee OA [23, 24, 42–44]. …”

Section: Discussionsupporting

confidence: 93%

“…The number of clinical randomized trials comparing different treatment and dosage is limited. In an interesting study, Orozco et al [24, 34] reported an improvement in pain and function with the use of a single intra-articular injection of 40 × 10 6 cultured autologous MSCs in twelve patients. In a more comparable randomized clinical trial, using allogenic MSCs, Vega et al reported good clinical outcomes in pain control and function when comparing the use of a single intra-articular injection of 40 × 10 6 cultured allogenic MSCs against a single intraarticular injection of HA [23].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, their number in a bone marrow concentrate is very limited compared to that obtained upon culturing MSCs [18–20]. Only a few studies using MSCs produced by good manufacture practices (GMP) such as advanced cell-therapy products have been reported [21–24]. In addition, there is a need to explore the effect of different cell doses in a randomized way to gain insight into the ideal conditions for knee OA patients to take advantage of MSC therapy.…”

Section: Introductionmentioning

confidence: 99%

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Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)

et al. 2016

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BackgroundMesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial.MaterialsA phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 10 × 106 or 100 × 106 cultured autologous BM-MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.ResultsNo adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009). BM-MSC-administered patients were also superior according to WOMAC, although improvement in control and low-dose patients could not be significantly sustained beyond 6 months. On the other hand, the BM-MSC high-dose group exhibited an improvement of 16.5 (12, 19) points at 12 months (p < 0.01). Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs. X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM-MSC high-dose group, albeit slightly.ConclusionsThe single intraarticular injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 × 106 cells are administered. These results pave the way for a future phase III clinical trial.Clinical Trials.gov identifier NCT02123368. Nº EudraCT: 2009-017624-72Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0998-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)

et al. 2016

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“…For the fate of MSCs in vivo , current studies are not conclusive on this question: some have suggested MSCs differentiate and survive in vivo up to 6 months, while others suggest MSCs have a chondroinductive role of stimulating cartilage regeneration through trophic factors while slowly disappearing from the culture26). BM-derived MSCs administered into knee have adhered to the surface of a damaged tissue, have differentiated into chondrocyte, and have expressed appropriate extracellular matrix protein, resulting in anatomic restoration on the damaged tissue with a significant relief of pain and disability16,21,22). Our meta-analysis found that MRI outcomes did not show a significant difference from baseline despite the pain and functional advantages of injected BM-derived MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Among our included articles, 6 studies16,19–22) met the ideal number of MSCs, 2 studies17,18) used less than 1×10 7 MSCs. For MSC characterization, 2 studies16,21) did not describe the expression of CD. This could result in poor MRI outcomes than expected.…”

Section: Discussionmentioning

confidence: 99%

Intra-Articular Injection of Bone Marrow-Derived Mesenchymal Stem Cells Leading to Better Clinical Outcomes without Difference in MRI Outcomes from Baseline in Patients with Knee Osteoarthritis

Shin

Yoon

Kim

et al. 2018

Knee Surg Relat Res

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PurposeBone marrow (BM) is frequently used as a source of mesenchymal stem cells (MSCs) because they have a high potential for differentiation. However, it is unclear whether BM-derived MSCs lead to better clinical and magnetic resonance imaging (MRI) outcomes postoperatively.Materials and MethodsThis meta-analysis compared the clinical and MRI outcomes in patients with knee osteoarthritis (OA) treated with BM-derived MSCs. Eight studies comparing the clinical and MRI outcomes assessed with various measurement tools in patients with knee OA treated with BM-derived MSCs were included.ResultsThe range of motion (95% confidence interval [CI], −13.05 to 4.24; p=0.32) and MRI outcomes (95% CI, −0.16 to 1.40; p=0.12) did not differ significantly between the baseline and final follow-up. In contrast, pain (95% CI, 0.89 to 1.87; p<0.001) and functional outcomes (95% CI, 0.70 to 2.07; p<0.001) were significantly improved at the final follow-up when compared to the baseline.ConclusionsThis meta-analysis found no significant difference in the tested range of motion and MRI outcomes between the baseline and the final follow-up in patients treated with BM-derived MSCs, whereas significant functional improvement and pain relief were noted when compared with the baseline. Thus, BM-derived MSCs appear to be a viable alternative for patients with knee OA, although long-term and high-quality randomized controlled trials are needed to confirm the clinical benefits.

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Management of knee osteoarthritis. Current status and future trends

Ondrésik

Maia

Morais

et al. 2016

Biotech & Bioengineering

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Osteoarthritis (OA) affects a large number of the population, and its incidence is showing a growing trend with the increasing life span. OA is the most prevalent joint condition worldwide, and currently, there is no functional cure for it. This review seeks to briefly overview the management of knee OA concerning standardized pharmaceutical and clinical approaches, as well as the new biotechnological horizons of OA treatment. The potential of biomaterials and state of the art of advanced therapeutic approaches, such as cell and gene therapy focused primarily on cartilage regeneration are the main subjects of this review. Biotechnol. Bioeng. 2017;114: 717-739. © 2016 Wiley Periodicals, Inc.

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Treatment of Knee Osteoarthritis With Autologous Mesenchymal Stem Cells

Cited by 198 publications

References 8 publications

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)

Intra-Articular Injection of Bone Marrow-Derived Mesenchymal Stem Cells Leading to Better Clinical Outcomes without Difference in MRI Outcomes from Baseline in Patients with Knee Osteoarthritis

Management of knee osteoarthritis. Current status and future trends

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