Background:Bone marrow aspirate concentrate (BMAC) has emerged as a novel treatment for pathology of the knee. Despite containing a limited number of stem cells, BMAC serves as a source of growth factors that are thought to play an important role as a result of their anabolic and anti-inflammatory effects. To our knowledge, there is no systematic review regarding the outcomes of bone marrow aspirate concentrate used for the treatment of chondral defects and osteoarthritis of the knee.Purpose:To perform a systematic review on the outcomes of bone marrow aspirate concentrate for the treatment of chondral defects and osteoarthritis of the knee.Study Design:Systematic review; Level of evidence, 4.Methods:A systematic review of the literature was performed using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, and MEDLINE from 1980 to present. Inclusion criteria were as follows: use of BMAC for treatment of chondral defects and osteoarthritis of the knee,...

https://journals.sagepub.com/doi/pdf/10.1177/2325967115625481

Concentrated Bone Marrow Aspirate for the Treatment of Chondral Injuries and Osteoarthritis of the Knee: A Systematic Review of Outcomes

The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place.

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The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

Background:Articular cartilage injury is frequently encountered, yet treatment options capable of providing durable cartilage repair are limited.Purpose:To investigate the medium-term clinical outcomes of cartilage repair using a 1-stage technique of a hyaluronic acid–based scaffold with activated bone marrow aspirate concentrate (HA-BMAC) and compare results with those of microfracture. A secondary aim of this study was to identify specific patient demographic factors and cartilage lesion characteristics that are associated with superior outcomes.Study Design:Cohort study; Level of evidence, 2.Methods:Fifty physically active patients (mean age, 45 years) with grade IV cartilage injury of the knee (lesion size, 1.5-24 cm2) were treated with HA-BMAC or microfracture and were observed prospectively for 5 years. Patients were placed into the HA-BMAC group if the health insurance policy of the treating institution supported this option; otherwise, they were placed into the microfracture group. Objective and s...

One-Stage Cartilage Repair Using a Hyaluronic Acid-Based Scaffold With Activated Bone Marrow-Derived Mesenchymal Stem Cells Compared With Microfracture: Five-Year Follow-up.

Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.

https://link.springer.com/content/pdf/10.1186%2Fs13018-016-0378-x.pdf

Stem cells in articular cartilage regeneration

Background: Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported.

Methods: We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score.

Results: Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82).

Conclusions: The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes.

Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis.

ObjectiveTo compare the outcome of matrix-induced autologous chondrocyte implantation (MACI) and bone marrow aspirate concentrate (BMAC)–derived multipotent stem cells (MSCs) implantation in patell...

/pdf/matrix-induced-autologous-chondrocyte-implantation-versus-2wkb1vrma3.pdf

Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial.

Context:Infection after anterior cruciate ligament reconstruction (ACLR) is uncommon; if it occurs, it can lead to disastrous complications.Objective:To analyze post-ACLR infections and identify re...

/pdf/postoperative-infection-after-anterior-cruciate-ligament-2ymhlh8saf.pdf

Postoperative Infection After Anterior Cruciate Ligament Reconstruction

The diagnosis of patellofemoral joint disorders is challenging for orthopaedic surgeons on the account of complicated pathophysiology that underlies them. The origin of patellofemoral symptoms is generally multifactorial, and therefore the clinical examination should take into account the patient as a whole, and meticulous attention must be drawn to the history, morphology and clinical examination to have a definitive diagnosis and address the patient’s pathology. It should be remembered that a proper therapeutic approach can only be engineered with a thorough analysis of the patients’ disorder.

Clinical Examination of the Patellofemoral Joint

Introduction: Bone marrow aspirate concentrate (BMAC) has been demonstrated to induce unfathomable healing activity in various forms of arthritis. On the other hand, viscosupplementation is widely used as one of the modalities to palliate the symptoms of knee osteoarthritis (OA). To the best of our knowledge, no research involving a comparison of the two interventions has been done. We evaluated and critically analyzed the comparative efficacy of an intra-articular injection of BMAC or sodium hyaluronate injection (Halonix; Cadila) in terms of pain relief or functional improvement using validated scoring instruments. Materials and Methods: Fifty patients of either sex, aged more than 18 years with grade 0 and grade 1 primary knee OA were randomized to receive intra-articular injection of either the mononuclear marrow concentrate or Halonix, and they were followed for 6 months. The patients treated received single injection either of mononuclear marrow concentrate or Halonix during the course of study. An independent, blinded evaluator assessed the patient with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the visual analog pain scale. Results: Both the cohorts treated with mononuclear marrow concentrate and with Halonix showed improvements from the baseline parameters at the end of 1-month follow-up. Group treated with BMAC showed significant difference (p<0.05) with respect to WOMAC, or visual analog scale results at the end of 6 months of follow-up. Men demonstrated significant improvement (p<0.05) in both the groups. Conclusion: Statistical significant differences were detected between patients treated with intra-articular injections of monocular marrow concentrate and those treated with the Halonix with respect to pain relief or function at 6 months of follow-up. Clinical Relevance: Direct delivery of bone marrow mononuclear concentrate to radiographic symptomatic grade 0 and grade 1 knee OA has the clinical potential to improve functional activity/ functional aspect of knee OA, providing a cost-effective approach for grade 0 and grade 1 knee OA.

Randomized blinded comparative analysis of autologous mononuclear medullary fraction and viscosupplementation in grade 0 and grade 1 radiographic scale of knee osteoarthritis

Articular cartilage injury in patellofemoral joint presents a clinical challenge and has been identified as a cause of pain, dysfunction and progressive joint degeneration. Any concomitant pathology such as objective or potential patellar instability, muscular dysfunction and biomechanical disorders of the foot and hip can act as a cause of patellofemoral pain syndrome and they should be investigated and addressed when necessary. Cartilage has a poor intrinsic healing potential. Therefore, when left untreated cartilage lesions can progress and lead to chondromalacia and early osteoarthritis (OA).

Sanyam Chaurasia

Papers

Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial.

Postoperative Infection After Anterior Cruciate Ligament Reconstruction

Clinical Examination of the Patellofemoral Joint

Randomized blinded comparative analysis of autologous mononuclear medullary fraction and viscosupplementation in grade 0 and grade 1 radiographic scale of knee osteoarthritis

Pulsed Electromagnetic Fields for the Treatment of Symptomatic Patellofemoral Cartilage Lesions of the Knee