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

Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the longterm efects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical efect. Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10×106 or 100×106 cultured autol‑ ogous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse efects and clinical evolution, assessed using VAS and WOMAC scorings are reported. Results: No adverse efects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-adminis‑ tered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p=0.01; High-dose vs Control group, p=0.004). Patients receiving BM-MSCs also improved clinically accord‑ ing to WOMAC. Control group showed an increase median value of 4 points (−11;10) while Low-dose and Highdose groups exhibited values of −18 (−28;−9) and −10 (−21;−3) points, respectively (Low-dose vs Control group p=0.043). No clinical diferences between the BM-MSCs receiving groups were found. Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible proce‑ dure that results in long-term clinical and functional improvement of knee OA

Meniscal Suture Influence on Driving Ability 6 Weeks after Anterior Cruciate Ligament Reconstruction with Hamstring Autograft

The purpose of this study was to determine if driving ability 6 weeks after anterior cruciate ligament (ACL) reconstruction is affected by the addition of a meniscal suture. It was also hypothesized that no differences in the driving performance would be found between right or left knee surgery subgroups. A total of 82 people participated in this prospective cohort study: 36 healthy controls, 26 patients undergoing isolated ACL (iACL) reconstruction with hamstring autograft, and 20 patients undergoing ACL and meniscal suture (ACL-MS) reconstruction. ACL-MS group followed a weight-bearing and movement restriction protocol during the first 2 postoperative weeks, whereas patients undergoing iACL could start range-of-motion exercises and full weight-bearing ambulation on the first postoperative day. A driving simulator that reproduced real-life driving conditions was used to evaluate driving ability. The software analyzed multiple driving and braking variables. Driving performance in the sixth postoperative week was compared with that of a healthy control group. Subgroup analysis considering additional procedures (iACL, ACL-MS) and the side of the operated knee (right, left) was also performed. No statistically significant differences were found in the demographic characteristics nor in the driving performance (collisions, p = 0.897; sidewalk invasions, p = 0.749; pedestrian impact, p = 0.983) between iACL, ACL-MS, and control groups. No statistically significant differences were found in right-left subgroup analysis. The results of the present study show that patients in their sixth postoperative week after right or left ACL reconstruction showed similar driving performance as compared with a healthy control group, regardless of associating or not a meniscal suture, suggesting it is safe to resume driving 6 weeks after the mentioned surgeries

Reconstruction of the extensor mechanism with fresh-frozen tendon allograft in total knee arthroplasty

Purpose: Patellar tendon rupture after total knee replacement is a rare and highly limiting injury with multifactorial aetiology. Many reconstruction techniques have been described with not very predictable results. The use of allografts has been accepted as a suitable solution. Methods: A series of seven patients with patellar tendon rupture treated with fresh-frozen tendon allograft reconstruction after knee arthroplasty is presented. Results: Median follow-up is 25 months (20-31). Functional assessment improved, and the knee society score and knee functional score improved from 26 and 16 to 82 and 55, respectively. Median extension lag was 5° (0°-20°), with a median range of motion of 95° (70-100). Radiological study showed a rise of the patella of 22.26 mm. Conclusion: The use of fresh-frozen allografts as a solution to patellar tendon ruptures after knee arthroplasty seems to provide acceptable results. Increased patellar height does not seem to affect functionality

Do we really improve life quality after total knee arthroplasty in patients with Parkinson’s disease?

Introduction The knee in Parkinson’s disease (PD) patients is a problematic joint due to pain, stifness and gait instability. The aim of this study is to evaluate the functional outcome and degree of pain relief achieved after total knee arthroplasty (TKA) in PD patients. Materials and methods This is a retrospective review of 26 PD patients (32 knees) with osteoarthritis who underwent a TKA between 1994 and 2013. Comorbidities, anesthetic procedures and complications were recorded. Patient functional status was assessed with the Knee Society Function Score (KFS) and the Knee Society Score (KSS). PD stage was classifed with the Hoehn and Yahr Scale. Results The mean follow-up was 3.5 years (range 2–9). The mean age was 71 years (range 61–83) with a mean time since PD diagnosis of 11.8 years (range 4–24). PD severity on the Hoehn and Yahr Scale was 1.5 points before surgery and 2 points postoperatively. Pain on the visual analogic scale improved from 8 points preoperatively to 5 points at 1-year follow-up; function improved from 32 (range 20–45) to 71 (range 50–81) and from 34 (range 28–52) to 59 (range 25–76) on the KSS and KFS, respectively. The mean postoperative hospital stay was 9.8 days (range 5–21). Confusion and fexion contracture were the most frequent perioperative complications. Conclusion TKA successfully provided pain relief in PD patients. However, the functional outcome is related to disease progression and, therefore, variable. Perioperative complications are difcult to avoid and manage

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

Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the longterm efects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical efect. Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10×106 or 100×106 cultured autol‑ ogous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse efects and clinical evolution, assessed using VAS and WOMAC scorings are reported. Results: No adverse efects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-adminis‑ tered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p=0.01; High-dose vs Control group, p=0.004). Patients receiving BM-MSCs also improved clinically accord‑ ing to WOMAC. Control group showed an increase median value of 4 points (−11;10) while Low-dose and Highdose groups exhibited values of −18 (−28;−9) and −10 (−21;−3) points, respectively (Low-dose vs Control group p=0.043). No clinical diferences between the BM-MSCs receiving groups were found. Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible proce‑ dure that results in long-term clinical and functional improvement of knee OA

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

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 100 × 106 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 100 × 106 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. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23

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

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 100 × 106 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 100 × 106 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. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23