scholarly journals Combined Autologous Chondrocyte and Bone Marrow Mesenchymal Stromal Cell Implantation in the Knee: An 8-year Follow Up of Two First-In-Man Cases

2019 ◽  
Vol 28 (7) ◽  
pp. 924-931
Author(s):  
Jingsong Wang ◽  
Karina T. Wright ◽  
Jade Perry ◽  
Bernhard Tins ◽  
Timothy Hopkins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Knee Function ◽  
Cartilage Defects ◽  
Repair Site ◽  
Cell Implantation ◽  
Autologous Chondrocyte

Autologous chondrocyte implantation (ACI) has been used to treat cartilage defects for >20 years, with promising clinical outcomes. Here, we report two first-in-man cases (patient A and B) treated with combined autologous chondrocyte and bone marrow mesenchymal stromal cell implantation (CACAMI), with 8-year follow up. Two patients with International Cartilage Repair Society (ICRS) grade III–IV cartilage lesions underwent a co-implantation of autologous chondrocytes and bone marrow-derived mesenchymal stromal cells (BM-MSCs) between February 2008 and October 2009. In brief, chondrocytes and BM-MSCs were separately isolated and culture-expanded in a good manufacturing practice laboratory for a period of 2–4 weeks. Cells were then implanted in combination into cartilage defects and patients were clinically evaluated preoperatively and postoperatively, using the self-reported Lysholm knee score and magnetic resonance imaging (MRI). Postoperative Lysholm scores were compared with the Oswestry risk of knee arthroplasty (ORKA) scores. Patient A also had a second-look arthroscopy, at which time a biopsy of the repair site was taken. Both patients demonstrated a significant long-term improvement in knee function, with postoperative Lysholm scores being consistently higher than ORKA predictions. The most recent Lysholm scores, 8 years after surgery were 100/100 (Patient A) and 88/100 (Patient B), where 100 represents a fully functioning knee joint. Bone marrow lesion (BML) volume was shown to decrease on postoperative MRIs in both patients. Cartilage defect area increased in patient A, but declined initially for patient B, slightly increasing again 2 years after treatment. The repair site biopsy taken from patient A at 14 months postoperatively, demonstrated a thin layer of fibrocartilage covering the treated defect site. The use of a combination of cultured autologous chondrocytes and BM-MSCs appears to confer long-term benefit in this two-patient case study. Improvements in knee function perhaps relate to the observed reduction in the size of the BML.

Bone marrow–mesenchymal stromal cell infusion in patients with chronic kidney disease: A safety study with 18 months of follow-up

Cytotherapy ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. 660-669 ◽  
Author(s):  
Atieh Makhlough ◽  
Soroosh Shekarchian ◽  
Reza Moghadasali ◽  
Behzad Einollahi ◽  
Mona Dastgheib ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Safety Study

scholarly journals Prospective Long-term Follow-up of Autologous Chondrocyte Implantation With Periosteum Versus Matrix-Associated Autologous Chondrocyte Implantation: A Randomized Clinical Trial

2020 ◽  
Vol 48 (9) ◽  
pp. 2230-2241
Author(s):  
Alexander Barié ◽  
Patrizia Kruck ◽  
Reza Sorbi ◽  
Christoph Rehnitz ◽  
Doris Oberle ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Autologous Chondrocyte Implantation ◽  
Cartilage Defects ◽  
Repair Tissue ◽  
Sf 36 ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte ◽  
Time Point

Background: Matrix-associated autologous chondrocyte implantation (MACI) is a further development of the original autologous chondrocyte implantation periosteal flap technique (ACI-P) for the treatment of articular cartilage defects. Purpose: We aimed to establish whether MACI or ACI-P provides superior long-term outcomes in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 21 patients with cartilage defects at the femoral condyle were randomized to MACI (n = 11) or ACI-P (n = 10) between the years 2004 and 2006. Patients were assessed for subjective International Knee Documentation Committee (IKDC) score, Lysholm and Gillquist score, Tegner Activity Score, and 36-Item Short Form Health Survey (SF-36) preoperatively (T0), at 1 and 2 years postoperatively (T1, T2), and at the final follow-up 8 to 11 years after surgery (T3). Onset of osteoarthritis was determined using the Kellgren-Lawrence score and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and delayed gadolinium-enhanced MRI of cartilage was used to evaluate the cartilage. Adverse events were recorded to assess safety. Results: There were 16 patients (MACI, n = 9; ACI-P, n = 7) who were reassessed on average 9.6 years after surgery (76% follow-up rate). The Lysholm and Gillquist score improved in both groups after surgery and remained elevated but reached statistical significance only in ACI-P at T1 and T2. IKDC scores increased significantly at all postoperative evaluation time points in ACI-P. In MACI, IKDC scores showed a significant increase at T1 and T3 when compared with T0. In the majority of the patients (10/16; MACI, 5/9; ACI-P, 5/7) a complete defect filling was present at the final follow-up as shown by the MOCART score, and 1 patient in the ACI-P group displayed hypertrophy of the repair tissue, which represents 6% of the whole study group and 14.3% of the ACI-P group. Besides higher SF-36 vitality scores in ACI-P at T3, no significant differences were seen in clinical scores and MRI scores between the 2 methods at any time point. Revision rate was 33.3% in MACI and 28.6% in ACI-P at the last follow-up. Conclusion: Our long-term results suggest that first- and third-generation ACI methods are equally effective treatments for isolated full-thickness cartilage defects of the knee. With the number of participants available, no significant difference was noted between MACI and ACI-P at any time point. Interpretation of our data has to be performed with caution due to the small sample size, which was further limited by a loss to follow-up of 24%.

scholarly journals Mosaicplasty versus Matrix-Assisted Autologous Chondrocyte Transplantation for Knee Cartilage Defects: A Long-Term Clinical and Imaging Evaluation

2020 ◽  
Vol 10 (13) ◽  
pp. 4615
Author(s):  
Stefano Zaffagnini ◽  
Angelo Boffa ◽  
Luca Andriolo ◽  
Davide Reale ◽  
Maurizio Busacca ◽  
...  
Keyword(s):  
Activity Level ◽  
Autologous Chondrocyte Transplantation ◽  
Cartilage Defects ◽  
Chondrocyte Transplantation ◽  
Knee Cartilage ◽  
Cartilage Lesions ◽  
Long Term Follow Up ◽  
Autologous Chondrocyte

Different surgical procedures have been proposed over the past few years to treat cartilage lesions. The aim of this study was to compare mosaicplasty and matrix-assisted autologous chondrocyte transplantation (MACT) at long-term follow-up. Forty-three patients were included: 20 mosaicplasty and 23 MACT. Patients were evaluated before and 12 years after surgery with the International Knee Documentation Committee (IKDC) subjective and objective scores for symptoms and function, and with the Tegner score for activity level. Magnetic Resonance Imaging (MRI) was used to evaluate repair tissue with the MOCART 2.0 score. Mosaicplasty and MACT showed good clinical and MRI results (IKDC subjective score 75.3 ± 21.8 and 81.8 ± 13.0, both p < 0.0005). Mosaicplasty presented a 10% reoperation rate and a 25% overall failure rate, while no failures were documented in MACT (p = 0.016). While size did not influence the results in the MACT group, mosaicplasty presented lower IKDC objective and Tegner scores in lesions bigger than 2 cm2 (p = 0.031 and p = 0.014, respectively). Mosaicplasty and MACT presented both satisfactory clinical and MRI results at long-term follow-up. However, for larger lesions, MACT presented better subjective and objective outcomes, as well as less failures, which should be considered when choosing the most suitable treatment for patients affected by knee cartilage lesions.

scholarly journals Bone marrow‐derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4‐year follow‐up of the MSC‐HF trial

2019 ◽  
Vol 22 (5) ◽  
pp. 884-892 ◽  
Author(s):  
Anders B. Mathiasen ◽  
Abbas A. Qayyum ◽  
Erik Jørgensen ◽  
Steffen Helqvist ◽  
Klaus F. Kofoed ◽  
...  
Keyword(s):  
Heart Failure ◽  
Bone Marrow ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell

scholarly journals Long-term Evaluation of Allogeneic Bone Marrow-derived Mesenchymal Stromal Cell Therapy for Crohn’s Disease Perianal Fistulas

2019 ◽  
Vol 14 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Marieke C Barnhoorn ◽  
Martin N J M Wasser ◽  
Helene Roelofs ◽  
P W Jeroen Maljaars ◽  
Ilse Molendijk ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Hla Antibodies ◽  
Perianal Fistulas

Abstract Background and Aims The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn’s disease [CD] fistulas is unknown. We aimed to provide a 4-year clinical evaluation of allogeneic bmMSC treatment of perianal CD fistulas. Methods A double-blind dose-finding study for local bmMSC therapy in 21 patients with refractory perianal fistulising Crohn’s disease was performed at the Leiden University Medical Center in 2012–2014. All patients treated with bmMSCs [1 x 107 bmMSCs cohort 1, n = 5; 3 × 107 bmMSCs cohort 2, n = 5; 9 × 107 bmMSCs cohort 3, n = 5] were invited for a 4-year evaluation. Clinical events were registered, fistula closure was evaluated, and anti-human leukocyte antigen [HLA] antibodies were assessed. Patients were also asked to undergo a pelvic magnetic resonance imaging [MRI] and rectoscopy. Results Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [n = 4] 63%, and in cohort 3 [n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy. Pelvic MRI showed significantly smaller fistula tracts after 4 years. Conclusions Allogeneic bmMSC therapy for CD-associated perianal fistulas is also in the long-term a safe therapy. In bmMSC-treated patients, fistulas with closure at Week 24 were still closed after 4 years.

scholarly journals Autologous chondrocyte implantation in the knee: systematic review and economic evaluation

2017 ◽  
Vol 21 (6) ◽  
pp. 1-294 ◽  
Author(s):  
Hema Mistry ◽  
Martin Connock ◽  
Joshua Pink ◽  
Deepson Shyangdan ◽  
Christine Clar ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Observational Studies ◽  
Health Technology ◽  
Long Term Results ◽  
Cartilage Defects ◽  
Chondrocyte Implantation ◽  
Articular Cartilage Defects ◽  
Autologous Chondrocyte

BackgroundThe surfaces of the bones in the knee are covered with articular cartilage, a rubber-like substance that is very smooth, allowing frictionless movement in the joint and acting as a shock absorber. The cells that form the cartilage are called chondrocytes. Natural cartilage is called hyaline cartilage. Articular cartilage has very little capacity for self-repair, so damage may be permanent. Various methods have been used to try to repair cartilage. Autologous chondrocyte implantation (ACI) involves laboratory culture of cartilage-producing cells from the knee and then implanting them into the chondral defect.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of ACI in chondral defects in the knee, compared with microfracture (MF).Data sourcesA broad search was done in MEDLINE, EMBASE, The Cochrane Library, NHS Economic Evaluation Database and Web of Science, for studies published since the last Health Technology Assessment review.Review methodsSystematic review of recent reviews, trials, long-term observational studies and economic evaluations of the use of ACI and MF for repairing symptomatic articular cartilage defects of the knee. A new economic model was constructed. Submissions from two manufacturers and the ACTIVE (Autologous Chondrocyte Transplantation/Implantation Versus Existing Treatment) trial group were reviewed. Survival analysis was based on long-term observational studies.ResultsFour randomised controlled trials (RCTs) published since the last appraisal provided evidence on the efficacy of ACI. The SUMMIT (Superiority of Matrix-induced autologous chondrocyte implant versus Microfracture for Treatment of symptomatic articular cartilage defects) trial compared matrix-applied chondrocyte implantation (MACI®) against MF. The TIG/ACT/01/2000 (TIG/ACT) trial compared ACI with characterised chondrocytes against MF. The ACTIVE trial compared several forms of ACI against standard treatments, mainly MF. In the SUMMIT trial, improvements in knee injury and osteoarthritis outcome scores (KOOSs), and the proportion of responders, were greater in the MACI group than in the MF group. In the TIG/ACT trial there was improvement in the KOOS at 60 months, but no difference between ACI and MF overall. Patients with onset of symptoms < 3 years’ duration did better with ACI. Results from ACTIVE have not yet been published. Survival analysis suggests that long-term results are better with ACI than with MF. Economic modelling suggested that ACI was cost-effective compared with MF across a range of scenarios.LimitationsThe main limitation is the lack of RCT data beyond 5 years of follow-up. A second is that the techniques of ACI are evolving, so long-term data come from trials using forms of ACI that are now superseded. In the modelling, we therefore assumed that durability of cartilage repair as seen in studies of older forms of ACI could be applied in modelling of newer forms. A third is that the high list prices of chondrocytes are reduced by confidential discounting. The main research needs are for longer-term follow-up and for trials of the next generation of ACI.ConclusionsThe evidence base for ACI has improved since the last appraisal by the National Institute for Health and Care Excellence. In most analyses, the incremental cost-effectiveness ratios for ACI compared with MF appear to be within a range usually considered acceptable. Research is needed into long-term results of new forms of ACI.Study registrationThis study is registered as PROSPERO CRD42014013083.FundingThe National Institute for Health Research Health Technology Assessment programme.

Feasibility of arthroscopic autologous chondrocyte implantation in the hip using an injectable hydrogel

2017 ◽  
Vol 28 (4) ◽  
pp. 442-449 ◽  
Author(s):  
Steffen Thier ◽  
Florian Baumann ◽  
Christel Weiss ◽  
Stefan Fickert
Keyword(s):  
Autologous Chondrocyte Implantation ◽  
Activity Level ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Short Term ◽  
Assessment Scores ◽  
Chondrocyte Implantation ◽  
Autologous Chondrocyte

Introduction: In the long term the treatment of articular cartilage defects of the hip has the most direct impact on the postoperative outcome and should diminish degenerative changes caused by different pathologies. The purpose of this prospective feasibility study is to describe technical aspects of arthroscopic, injectable autologous chondrocyte implantation in the hip and to report the short-term outcome. Methods: Full-thickness cartilage defects of 13 patients were treated arthroscopically with an injectable autologous chondrocyte transplantation product (Novocart Inject, Tetec) in a 2-step surgical procedure. Patient-related outcome was assessed with iHOT 33, EQ-5D and Non Arthritic Hip Score at baseline (day before transplantation), after 6 weeks and 3, 6 and 12 months. Results: 13 out of 13 patients (all men) with a mean age of 32.7 ± 6.9 years and an average defect size of 1.9 ± 1.0 cm2 were available for follow-up after a mean of 12 months (range 6-24 months). All defects were located on the acetabulum and 11 were associated with a labral lesion of 2.9 hours size. Femoroacetabular impingement (10 cam, 2 combined, 1 pincer) was the cause of all defects. An overall statistically significant improvement was observed for all assessment scores. Conclusions: In this study we present the feasibility and short-term data of an arthroscopic injectable autologous chondrocyte transplant as a treatment option for full-thickness cartilage defects of the hip. All patient-administered assessment scores demonstrated an increase in activity level, improvement in quality of life and reduction of pain after a 12-month follow-up. Further randomised controlled trails with long-term follow-up and additional morphological assessment are needed.

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