Cartilage regeneration using human umbilical cord blood derived mesenchymal stem cells: A systematic review and meta-analysis

Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle–Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10–37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17–6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis

Autologous collagen-induced chondrogenesis: From bench to clinical development

Microfracture is a common technique that uses bone marrow components to stimulate cartilage regeneration. However, the clinical results of microfracture range from poor to good. To enhance cartilage healing, several reinforcing techniques have been developed, including porcine-derived collagen scaffold, hyaluronic acid, and chitosan. Autologous collagen-induced chondrogenesis (ACIC) is a single-step surgical technique for cartilage regeneration that combines gel-type atelocollagen scaffolding with microfracture. Even though ACIC is a relatively new technique, literature show excellent clinical results. In addition, all procedures of ACIC are performed arthroscopically, which is increasing in preference among surgeons and patients. The ACIC technique also is called the Shetty–Kim technique because it was developed from the works of A.A. Shetty and S.J. Kim. This is an up-to-date review of the history of ACIC

Gel-type autologous chondrocyte (Chondron™) implantation for treatment of articular cartilage defects of the knee

<p>Abstract</p> <p>Background</p> <p>Gel-type autologous chondrocyte (Chondron™) implantations have been used for several years without using periosteum or membrane. This study involves evaluations of the clinical results of Chondron™ at many clinical centers at various time points during the postoperative patient follow-up.</p> <p>Methods</p> <p>Data from 98 patients with articular cartilage injury of the knee joint and who underwent Chondron™ implantation at ten Korean hospitals between January 2005 and November 2008, were included and were divided into two groups based on the patient follow-up period, i.e. 13~24-month follow-up and greater than 25-month follow-up. The telephone Knee Society Score obtained during telephone interviews with patients, was used as the evaluation tool.</p> <p>Results</p> <p>On the tKSS-A (telephone Knee Society Score-A), the score improved from 43.52 ± 20.20 to 89.71 ± 13.69 (P < 0.05), and on the tKSS-B (telephone Knee Society Score-B), the score improved from 50.66 ± 20.05 to 89.38 ± 15.76 (P < 0.05). The total improvement was from 94.18 ± 31.43 to 179.10 ± 24.69 (P < 0.05).</p> <p>Conclusion</p> <p>Gel-type autologous chondrocyte implantation for chondral knee defects appears to be a safe and effective method for both decreasing pain and improving knee function.</p

Use of injectable acellular dermal matrix combined with negative pressure wound therapy in open diabetic foot amputation

Objective: Skin grafts after negative pressure wound therapy (NPWT) and acellular dermal matrix (ADM) usage have both been useful for treating diabetic foot amputation. We hypothesised that injectable ADM combined with NPWT would be more useful than NPWT only for healing after amputation in patients with diabetic foot ulcers (DFUs). The aim of this study was to investigate the clinical outcomes of injectable ADM combined with NPWT in patients with DFU who have undergone amputation. Method: This retrospective study reviewed patients with infected DFUs who were administered NPWT. Patients were divided into two groups: Group 1 included patients who were treated with NPWT only, while Group 2 included patients who were treated with injectable ADM combined with NPWT. Clinical results including the number of NPWT dressing changes, wound healing duration, and full-thickness skin graft (FTSG) incident rate between the two groups were compared. Results: A total of 41 patients took part in the study (Group 1=20, Group 2=21). The mean number of NPWT dressing changes was significantly lower in Group 2 (8.71±3.77) than in Group 1 (13.90±5.62) (p=0.001). Mean wound healing period was shorter in Group 2 (3.17±1.36 weeks) than in Group 1 (5.47±1.68 weeks) (p=0.001). Finally, the rate of patients who underwent FTSG for complete wound closure was 85% in Group 1, whereas it was only 14.3% in Group 2. Conclusion: In this study, the use of injectable ADM combined with NPWT in patients with DFU who underwent amputation favoured complete wound healing, without the need to resort to the use of skin grafts

Biological reconstruction of the joint: Concepts of articular cartilage regeneration and their scientific basis

Articular cartilage injuries are common. The diagnosis of these injuries is often delayed and may lead to early osteoarthritis. Treatment depends on many factors but mainly on the stage and size of the lesion. The anatomy of articular cartilage is complex, and it is an avascular, aneural, and alymphatic structure. Recently, more emphasis is laid on its anatomy and biomechanics to understand the regeneration process of articular cartilage. [Abstract copyright: © 2021 Delhi Orthopedic Association. All rights reserved.

A combination of surgical and chemical induction in a rabbit model for osteoarthritis of the knee

Appropriate animal models of osteoarthritis (OA) are essential to develop new treatment modalities for OA. A combination of surgical and chemical induction could be appropriate for OA models. Rabbit knee OA models developed by surgical induction (anterior cruciate ligament transection [ACLT]), chemical induction (monosodium iodoacetate [MIA] injection), and a combination of both were compared to assess compositional and structural destruction of the knee joint. Twenty-one New Zealand white rabbits were randomly divided into 3 groups to induce OA (group 1: ACLT, n = 3; group 2: MIA [3, 6, 9 mg] injection, n = 9; group 3: ACLT + MIA [3, 6, 9 mg] injection, n = 9). In all groups, the Modified Mankin score was significantly higher in the osteoarthritis-induced knee than in the control. Modified Mankin scores were compared by category. The ACLT group was observed to score high in cartilage structure. In the MIA group, chondrocytes and matrix staining showed higher scores, and the ACLT+MIA group scored higher in all categories for cartilage structure, chondrocytes, matrix staining, and tidemark integrity. The ACLT + 3 mg MIA showed definite OA characteristics such as cartilage surface destruction and degeneration of cartilage layers, and the ACLT + 6 mg MIA and ACLT + 9 mg MIA showed more prominent OA characteristics such as cartilage surface destruction, matrix disorganization, and osteophyte formation. The combination of MIA injection and ACLT could be an appropriate method for OA induction in rabbit models. [Abstract copyright: © 2022. Korean Tissue Engineering and Regenerative Medicine Society.

Cell therapy for osteonecrosis of femoral head and joint preservation

Osteonecrosis of femoral head (ONFH) is a disease of the femoral head and can cause femoral head collapse and arthritis. This can lead to pain and gait disorders. ONFH has various risk factors, it is often progressive, and if untreated results in secondary osteo-arthritis. Biological therapy makes use of bone marrow concentrate, cultured osteoblast and mesenchymal stem cell (MSC) obtained from various sources. These are often used in conjunction with core decompression surgery. In this review article, we discuss the current status of cell therapy and its limitations. We also present the future development of biological approach to treat ONFH. [Abstract copyright: © 2021.

Cartilage Regeneration Using Human Umbilical Cord Blood Derived Mesenchymal Stem Cells: A Systematic Review and Meta-Analysis

Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle–Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p 2 = 93%, p p 2 = 95%, p p 2 = 98%, p Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis

Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates.

Venous blood drained from the knee joint after total knee arthroplasty (TKA) using a hemovac line is a potential source of bone marrow components, including stem cells, from the cutting surface of cancellous bones of the knee joint. However, the function of mesenchymal stem cells (MSCs) in patients with osteoarthritis (OA-MSCs) can be disrupted by inflammation of the joint. Further, to override the invasive nature of the currently used methods to obtain stem cells, their functional modification is necessary for therapeutic applications. The effects of signal transducer and activator of transcription 3 (STAT3) signaling suppression on MSCs (iSTAT3-MSCs) were evaluated by comparative analyses of the characteristics of OA-MSCs and iSTAT3-MSCs from 20 patients who underwent TKA. OA-MSCs and iSTAT3-MSCs were adherent, with fibroblast-like appearance and high rates of expression of MSC-specific markers, including CD73, CD90, and CD105 (>90%). Both OA-MSCs and iSTAT3-MSCs were able to differentiate into osteogenic, adipogenic, and chondrogenic cells; however, iSTAT3-MSCs showed higher levels of osteogenic and chondrogenic differentiation markers than OA-MSCs. Additionally, the anti-inflammatory and chondroprotective cytokine levels were higher in iSTAT3-MSCs than in OA-MSCs. These findings indicate that iSTAT3-MSCs after TKA are potentially effective for stem cell therapy in the context of bone and cartilage disorders. [Abstract copyright: 2021 Annals of Translational Medicine. All rights reserved.

Improved healing of rabbit patellar tendon defects after an atelocollagen injection

Patellar tendinopathy is a common cause of limitations in daily life activities in young and/or active people. The patellar tendon consists of a complex of collagen fibers; therefore, collagen could be used as a scaffold in the treatment of patellar tendinopathy. To evaluate the healing capacity of injected atelocollagen as a treatment scaffold for patellar tendon defect and, hence, its potential for the treatment of patellar tendinopathy. Controlled laboratory study. After receiving a full-thickness patellar tendon defect, 24 New Zealand White rabbits were divided into a control group (without treatment) and an experimental group that received an atelocollagen injection into the defect. Six rabbits from each group were subsequently used for either histologic scoring or biomechanical testing. The Mann-Whitney test was used to compare histologic evaluation scores and load to failure between the 2 groups. Statistical significance was set at < .05. The experimental group showed excellent repair of the damaged patellar tendon and good remodeling of the defective area. In contrast, the control group showed defective healing with loose, irregular matrix fibers and adipose tissue formation. A statistically significant difference was found between the 2 groups in both histologic scores and biomechanical tests at postoperative week 12. Injection of atelocollagen significantly improved the regeneration of damaged patellar tendons. Atelocollagen gel injections could be used to treat patellar tendinopathy in outpatient clinic settings