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Ghasemi SA, Kolesnick E, Murray BC, Leiby BE, Bartolozzi AR, Zaslav KR. High tibial osteotomy combined with cartilage restoration: A systematic review of clinical outcomes and prognostic factors. J Clin Orthop Trauma 2024; 50:102360. [PMID: 38425335 PMCID: PMC10899021 DOI: 10.1016/j.jcot.2024.102360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 01/11/2024] [Accepted: 02/05/2024] [Indexed: 03/02/2024] Open
Abstract
Background Focal chondral defects are often treated with cartilage restoration procedures. Malalignment often accompanies chondral defects. High tibial osteotomy (HTO), classically utilized to treat uni-compartmental knee osteoarthritis, corrects malalignment. HTO combined with cartilage restoration procedures can treat uni-compartmental osteoarthritis and focal chondral defects. Purpose To assess outcomes of combined HTO and cartilage restoration procedures and review prognostic factors that may assist in preoperative planning and patient counseling. Study design Systematic Review of published literature. Methods A systematic review of PubMed and Scopus was performed following PRISMA guidelines. Thirty-four papers were included in qualitative considerations. Results Thirty-four papers that reported the combined outcome of HTO and cartilage repair were included. Twenty of the 34 included papers reported prognostic factors that affected the success or failure of combined HTO and cartilage repair surgery for focal articular defect and uni-compartmental knee osteoarthritis. Cartilage repair techniques that were combined with HTO and included in this review are bone marrow stimulation, allograft transplantation, osteochondral autograft transplantation, autologous chondrocyte implantation, and mesenchymal stem cell implantation. Conclusions HTO with adjunctive cartilage repair procedures improve clinical outcome scores and restore alignment in patients with medial compartment osteoarthritis and isolated focal chondral defects. HTO with adjunctive cartilage procedures produces optimal results in younger, non-obese patients with focal chondral defects and varus malalignment, without significant lateral compartment and patellofemoral involvement.
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Affiliation(s)
- S. Ali Ghasemi
- Department of Orthopaedic Surgery, Albert Einstein Health Network, 5501 Old York Road, Philadelphia, PA, 19141, USA
| | - Evan Kolesnick
- Philadelphia College of Osteopathic Medicine, 4170 City Ave, Philadelphia, PA, 19131, USA
| | - Benjamin C. Murray
- Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA, 23708, USA
| | - Benjamin E. Leiby
- Thomas Jefferson University Sidney Kimmel Medical College, 1025 Walnut Street, Philadelphia, PA, 19107, USA
| | - Arthur R. Bartolozzi
- Department of Orthopaedic Surgery, Jefferson Health – Northeast, 380 North Oxford Valley Road, Langhorne, PA, 19047, USA
| | - Kenneth R. Zaslav
- Department of Orthopaedic Surgery, Northwell Health/Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Blvd, Hempstead, NY, 11549, USA
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Saw KY, Anz AW, Jee CSY, Low SF, Dawam A, Ramlan A. Osteochondral Regeneration in the Knee Joint with Autologous Peripheral Blood Stem Cells plus Hyaluronic Acid after Arthroscopic Subchondral Drilling: Report of Five Cases. Orthop Surg 2024; 16:506-513. [PMID: 38087402 PMCID: PMC10834187 DOI: 10.1111/os.13949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND Treatment of osteochondral defects (OCDs) of the knee joint remains challenging. The purpose of this study was to evaluate the clinical and radiological results of osteochondral regeneration following intra-articular injections of autologous peripheral blood stem cells (PBSC) plus hyaluronic acid (HA) after arthroscopic subchondral drilling into OCDs of the knee joint. CASE PRESENTATION Five patients with OCDs of the knee joint are presented. The etiology includes osteochondritis dissecans, traumatic knee injuries, previously failed cartilage repair procedures involving microfractures and OATS (osteochondral allograft transfer systems). PBSC were harvested 1 week after surgery. Patients received intra-articular injections at week 1, 2, 3, 4, and 5 after surgery. Then at 6 months after surgery, intra-articular injections were administered at a weekly interval for 3 consecutive weeks. These 3 weekly injections were repeated at 12, 18 and 24 months after surgery. Each patient received a total of 17 injections. Subjective International Knee Documentation Committee (IKDC) scores and MRI scans were obtained preoperatively and postoperatively at serial visits. At follow-ups of >5 years, the mean preoperative and postoperative IKDC scores were 47.2 and 80.7 respectively (p = 0.005). IKDC scores for all patients exceeded the minimal clinically important difference values of 8.3, indicating clinical significance. Serial MRI scans charted the repair and regeneration of the OCDs with evidence of bone growth filling-in the base of the defects, followed by reformation of the subchondral bone plate and regeneration of the overlying articular cartilage. CONCLUSION These case studies showed that this treatment is able to repair and regenerate both the osseous and articular cartilage components of knee OCDs.
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Affiliation(s)
- Khay-Yong Saw
- Orthopaedics, Kuala Lumpur Sports Medicine Centre, Kuala Lumpur, Malaysia
| | - Adam W Anz
- Sports Medicine Orthopedic Surgery, Andrews Institute, Gulf Breeze, FL, USA
| | - Caroline Siew-Yoke Jee
- Orthopaedics, Kuala Lumpur Sports Medicine Centre, Kuala Lumpur, Malaysia
- R&D, KLSMC Stem Cells, Kuala Lumpur, Malaysia
| | - Soo-Fin Low
- Radiology, Kuala Lumpur Sports Medicine Centre, Kuala Lumpur, Malaysia
| | - Amal Dawam
- R&D, KLSMC Stem Cells, Kuala Lumpur, Malaysia
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Jeyaraman M, Nallakumarasamy A, Jeyaraman N, Ramasubramanian S. Tissue engineering in chondral defect. COMPUTATIONAL BIOLOGY FOR STEM CELL RESEARCH 2024:361-378. [DOI: 10.1016/b978-0-443-13222-3.00033-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Reale D, Feltri P, Franceschini M, de Girolamo L, Laver L, Magalon J, Sanchez M, Tischer T, Filardo G. Biological intra-articular augmentation for osteotomy in knee osteoarthritis: strategies and results : A systematic review of the literature from the ESSKA Orthobiologics Initiative. Knee Surg Sports Traumatol Arthrosc 2023; 31:4327-4346. [PMID: 37330935 DOI: 10.1007/s00167-023-07469-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023]
Abstract
PURPOSE To assess whether there is evidence supporting the use of augmentation strategies, either cartilage surgical procedures or injective orthobiologic options, to improve the results of osteotomies in knees with osteoarthritis (OA). METHODS A systematic review of the literature was performed on the PubMed, Web of Science and the Cochrane databases in January 2023 on osteotomies around the knee associated with augmentation strategies (either cartilage surgical procedures or injective orthobiologic options), reporting clinical, radiological, or second-look/histological outcomes at any follow-up. The methodological quality of the included studies was assessed with the Coleman Methodology Score (CMS). RESULTS Out of the 7650 records identified from the databases, 42 articles were included for a total of 3580 patients and 3609 knees treated; 33 articles focused on surgical treatments and 9 on injective treatments performed in association with knee osteotomy. Out of the 17 comparative studies with surgical augmentation, only 1 showed a significant clinical benefit of an augmentation procedure with a regenerative approach. Overall, other studies showed no differences with reparative techniques and even detrimental outcomes with microfractures. Regarding injective procedures, viscosupplementation showed no improvement, while the use of platelet-rich plasma or cell-based products derived from both bone marrow and adipose tissue showed overall positive tissue changes which translated into a clinical benefit. The mean modified CMS score was 60.0 ± 12.1. CONCLUSION There is no evidence to support the effectiveness of cartilage surgical treatments combined with osteotomies in terms of pain relief and functional recovery of patients affected by OA in misaligned joints. Orthobiologic injective treatments targeting the whole joint environment showed promising findings. However, overall the available literature presents a limited quality with only few heterogeneous studies investigating each treatment option. This ORBIT systematic analysis will help surgeons to choose their therapeutic strategy according to the available evidence, and to plan further and better studies to optimize biologic intra-articular osteotomy augmentation. LEVEL OF EVIDENCE Level IV.
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Affiliation(s)
- Davide Reale
- Ortopedia e Traumatologia, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Pietro Feltri
- Service of Orthopaedics and Traumatology, Department of Surgery, EOC, 6900, Lugano, Switzerland
| | - Marco Franceschini
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli-1, 40136, Bologna, Italy.
| | - Laura de Girolamo
- Orthopaedic Biotechnology Laboratory, IRCCS Istituto Ortopedico Galeazzi, 20161, Milan, Italy
| | - Lior Laver
- Department of Orthopaedics, Hillel Yaffe Medical Center (HYMC), 38100, Hadera, Israel
- Arthrosport Clinic, Tel-Aviv, Israel
- Rappaport Faculty of Medicine, Technion University Hospital, Israel Institute of Technology, 32000, Haifa, Israel
| | - Jeremy Magalon
- Cell Therapy Department, Hôpital de la Conception, Assistance Publique des Hôpitaux de Marseille (AP-HM), INSERM CIC BT 1409, 13005, Marseille, France
- INSERM, INRA, C2VN, Aix Marseille Univ, 13005, Marseille, France
- SAS Remedex, 13008, Marseille, France
| | - Mikel Sanchez
- Arthroscopic Surgery Unit, Hospital Vithas Vitoria, 01008, Vitoria-Gasteiz, Spain
- Advanced Biological Therapy Unit, Hospital Vithas Vitoria, 01008, Vitoria-Gasteiz, Spain
| | - Thomas Tischer
- Department of Orthopaedic Surgery, University of Rostock, 18051, Rostock, Germany
| | - Giuseppe Filardo
- Service of Orthopaedics and Traumatology, Department of Surgery, EOC, 6900, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900, Lugano, Switzerland
- Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, 40136, Bologna, Italy
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Ghasemi SA, Murray BC, Buksbaum JR, Shin J, Fragomen A, Rozbruch SR. Opening wedge high tibial osteotomy for medial compartment knee osteoarthritis: Planning and improving outcomes: Case series and literature review. J Clin Orthop Trauma 2023; 36:102085. [PMID: 36654729 PMCID: PMC9840976 DOI: 10.1016/j.jcot.2022.102085] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Background Opening wedge high tibial osteotomy (OWHTO) is a safe surgical procedure to treat medial compartmental osteoarthritis caused by a varus deformity. Over-correction of this varus deformity can lead to lateral compartment over-loading. In our study, we planned our correction by using the mechanical axis deviation (MAD). Purpose The purpose of this study is to evaluate the clinical and radiological results of OWHTO based on planning using the MAD measurements. Study Design Retrospective Case Series. Methods 14 patients with Kellgren- Lawrence classification (KL) grade 3 or above underwent OWHTO, with plans to have the mechanical axis pass through 5-15 mm lateral to the center of the tibial plateau. Pre-operative and post-operative radiographic measurements were made and compared using the student t-test. SF-36 scores were obtained for clinical performance. Results Our patients experienced MAD from 25.9 mm medial to the center of the tibial plateau pre-operatively to 12.7 mm lateral to the center of the plateau post-operatively. The mean change in MAD was 38.7 mm (p < 0.0001). The accuracy of our correction compared to the planned MAD was 98.3%. The mechanical axis angle shifted from 7.35° of varus to 3.5° of valgus (p < 0.0001). All patients had post-operative alignments of 1-6° of valgus, with 11 of out the 14 patients with alignments less than 5° of valgus, preventing over-loading of the lateral compartment. Conclusion Using MAD measurements is an accurate planning method for OWHTO that corrects varus deformity without over-loading the lateral compartment, and leads to improved clinical outcomes.
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Affiliation(s)
- S. Ali Ghasemi
- Orthopaedic Surgery, Albert Einstein Health Network, Philadelphia, PA, 19141, United States
| | - Benjamin C. Murray
- Philadelphia College of Osteopathic Medicine, Philadelphia, PA, 19131, United States
| | - Joshua R. Buksbaum
- Limb Lengthening and Complex Reconstruction Service, Weill Cornell Medical College Department of Orthopaedic Surgery, Hospital for Special Surgery New York, NY, 10021, United States
| | - Jonggu Shin
- Limb Lengthening and Complex Reconstruction Service, Weill Cornell Medical College Department of Orthopaedic Surgery, Hospital for Special Surgery New York, NY, 10021, United States
| | - Austin Fragomen
- Limb Lengthening and Complex Reconstruction Service, Weill Cornell Medical College Department of Orthopaedic Surgery, Hospital for Special Surgery New York, NY, 10021, United States
| | - S Robert Rozbruch
- Limb Lengthening and Complex Reconstruction Service, Weill Cornell Medical College Department of Orthopaedic Surgery, Hospital for Special Surgery New York, NY, 10021, United States
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Kim JH, Kim KI, Yoon WK, Song SJ, Jin W. Intra-articular Injection of Mesenchymal Stem Cells After High Tibial Osteotomy in Osteoarthritic Knee: Two-Year Follow-up of Randomized Control Trial. Stem Cells Transl Med 2022; 11:572-585. [PMID: 35674255 PMCID: PMC9216209 DOI: 10.1093/stcltm/szac023] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 03/20/2022] [Indexed: 02/02/2023] Open
Abstract
Intra-articular injection of adipose-derived mesenchymal stem cell (ADMSC) after medial open-wedge high tibial osteotomy (MOWHTO) would be a promising disease-modifying treatment by correcting biomechanical and biochemical environment for arthritic knee with varus malalignment. However, there is a paucity of clinical evidence of the treatment. This randomized controlled trial (RCT) was aimed to assess regeneration of cartilage defect, functional improvement, and safety of intra-articular injection of ADMSCs after MOWHTO compared with MOWHTO alone for osteoarthritic knee with varus malalignment. This RCT allocated 26 patients into the MOWHTO with ADMSC-injection group (n = 13) and control (MOWHTO-alone) group (n = 13). The primary outcome was the serial changes of cartilage defect on periodic magnetic resonance imaging (MRI) evaluation using valid measurements until postoperative 24 months. Secondary outcomes were the 2-stage arthroscopic evaluation for macroscopic cartilage status and the postoperative functional improvements of patient-reported outcome measures until the latest follow-up. Furthermore, safety profiles after the treatment were evaluated. Cartilage regeneration on serial MRIs showed significantly better in the ADMSC group than in the control group. The arthroscopic assessment revealed that total cartilage regeneration was significantly better in the ADMSC group. Although it was not significant, functional improvements after the treatment showed a tendency to be greater in the ADMSC group than in the control group from 18 months after the treatment. No treatment-related adverse events, serious adverse events, and postoperative complications occurred in all cases. Concomitant intra-articular injection of ADMSCs with MOWHTO had advantages over MOWHTO alone in terms of cartilage regeneration with safety at 2-year follow-up, suggesting potential disease-modifying treatment for knee OA with varus malalignment.
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Affiliation(s)
- Jun-Ho Kim
- Department of Orthopaedic Surgery, Center for Joint Diseases, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea
| | - Kang-Il Kim
- Corresponding author: Kang-Il Kim, M.D., Ph D., Department of Orthopedic Surgery, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul 134-727, Republic of Korea. Tel: +82 2 440 6151;
| | - Wan Keun Yoon
- Department of Orthopaedic Surgery, Center for Joint Diseases, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea
| | - Sang-Jun Song
- Department of Orthopaedic Surgery, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Wook Jin
- Department of Radiology, Kyung Hee University Hospital at Gandong, Seoul, Republic of Korea
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Faber S, Angele P, Zellner J, Bode G, Hochrein A, Niemeyer P. Comparison of Clinical Outcome following Cartilage Repair for Patients with Underlying Varus Deformity with or without Additional High Tibial Osteotomy: A Propensity Score-Matched Study Based on the German Cartilage Registry (KnorpelRegister DGOU). Cartilage 2021; 13:1206S-1216S. [PMID: 33371734 PMCID: PMC8808839 DOI: 10.1177/1947603520982347] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Even though realignment procedures have gained popularity as concomitant techniques in cartilage repair approaches with underlying malalignment, the clinical efficacy has not been proven to full extent. METHODS Out of 5474 patients from the German Cartilage Registry, 788 patients with focal cartilage defects on the medial femoral condyle having received either no accompanying surgery or high tibial osteotomy (HTO) were identified. After a 1:1 propensity score matching, outcome of 440 patients was evaluated using KOOS (Knee Injury and Osteoarthritis Outcome Score), VAS (visual analogue scale), and satisfaction during the 3-year follow-up. RESULTS Patients having received a concomitant HTO had significantly higher postoperative KOOS values (12 months: 67.26 ± 15.69 vs.75.10 ± 16.12, P = 0.001; 24 months: 67.14 ± 23.85 vs. 77.11 ± 16.50, P = 0.010; 36 months: 74.40 ± 16.57 vs. 81.75 ± 14.22, P = 0.023) and lower pain levels (6 months: 3.43 ± 2.18 vs. 2.89 ± 2.15, P = 0.009; 12 months: 3.64 ± 2.20 vs. 2.17 ± 1.96, P < 0.001; 24 months: 4.20 ± 3.12 vs. 2.94 ± 2.45, P = 0.005; 36 months: 3.20 ± 2.18 vs. 2.02 ± 1.98, P = 0.003). One and 3 years postoperatively, concomitant HTO led to significantly higher satisfaction in patients. These advantages of accompanying HTO were also seen in the group of patients with a varus deformity of 5° or more, in which pain levels without concomitant HTO even increased during the 3-year follow-up. CONCLUSION The results of the present study underline the importance and safety of concomitant HTO in patients with cartilage defects and varus deformity. HTO should therefore be considered and recommended generously in patients with focal cartilage defects of the medial femoral condyle and varus deformity.
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Affiliation(s)
- Svea Faber
- OCM
- Orthopädische Chirurgie München,
Munich, Germany
| | - Peter Angele
- Sporthopaedicum, Berlin, Germany,Sporthopaedicum, Straubing,
Germany,Sporthopaedicum, Regensburg,
Germany,Klinik für Unfallchirurgie,
Universitätsklinikum, Regensburg, Bayern, Germany
| | - Johannes Zellner
- Klinik für Unfallchirurgie,
Caritas-Krankenhaus St. Josef Regensburg, Bayern, Germany
| | - Gerrit Bode
- Sporthopaedicum, Berlin, Germany,Sporthopaedicum, Straubing,
Germany,Sporthopaedicum, Regensburg,
Germany,Klinik für Orthopädie und Traumatologie,
Universitätsklinikum Freiburg, Baden-Württemberg, Germany
| | | | - Philipp Niemeyer
- OCM
- Orthopädische Chirurgie München,
Munich, Germany,Klinik für Orthopädie und Traumatologie,
Universitätsklinikum Freiburg, Baden-Württemberg, Germany,Philipp Niemeyer, OCM
- Orthopädische
Chirurgie München, Steinerstrasse 6, Munich, 812306, Germany.
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Anz AW, Torres J, Plummer HA, Siew-Yoke Jee C, Dekker TJ, Johnson KB, Saw KY. Mobilized Peripheral Blood Stem Cells are Pluripotent and Can Be Safely Harvested and Stored for Cartilage Repair. Arthroscopy 2021; 37:3347-3356. [PMID: 33940122 DOI: 10.1016/j.arthro.2021.04.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 04/06/2021] [Accepted: 04/15/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The primary objective of this study was to reproduce and validate the harvest, processing and storage of peripheral blood stem cells for a subsequent cartilage repair trial, evaluating safety, reliability, and potential to produce viable, sterile stem cells. METHODS Ten healthy subjects (aged 19-44 years) received 3 consecutive daily doses of filgrastim followed by an apheresis harvest of mononuclear cells on a fourth day. In a clean room, the apheresis product was prepared for cryopreservation and processed into 4 mL aliquots. Sterility and qualification testing were performed pre-processing and post-processing at multiple time points out to 2 years. Eight samples were shipped internationally to validate cell transport potential. One sample from all participants was cultured to test proliferative potential with colony forming unit (CFU) assay. Five samples, from 5 participants were tested for differentiation potential, including chondrogenic, adipogenic, osteogenic, endoderm, and ectoderm assays. RESULTS Fresh aliquots contained an average of 532.9 ± 166. × 106 total viable cells/4 mL vial and 2.1 ± 1.0 × 106 CD34+ cells/4 mL vial. After processing for cryopreservation, the average cell count decreased to 331.3 ± 79. × 106 total viable cells /4 mL vial and 1.5 ± 0.7 × 106 CD34+ cells/4 mL vial CD34+ cells. Preprocessing viability averaged 99% and postprocessing 88%. Viability remained constant after cryopreservation at all subsequent time points. All sterility testing was negative. All samples showed proliferative potential, with average CFU count 301.4 ± 63.9. All samples were pluripotent. CONCLUSIONS Peripheral blood stem cells are pluripotent and can be safely harvested/stored with filgrastim, apheresis, clean-room processing, and cryopreservation. These cells can be stored for 2 years and shipped without loss of viability. CLINICAL RELEVANCE This method represents an accessible stem cell therapy in development to augment cartilage repair.
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Affiliation(s)
- Adam W Anz
- Andrews Institute for Orthopedics & Sports Medicine, Gulf Breeze; Andrews Research & Education Foundation, Gulf Breeze.
| | - Johnny Torres
- Andrews Research & Education Foundation, Gulf Breeze
| | | | | | | | | | - Khay-Yong Saw
- Kuala Lumpur Sports Medicine Centre, Kuala Lumpur, Malaysia
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Arthroscopic Subchondral Drilling Followed by Injection of Peripheral Blood Stem Cells and Hyaluronic Acid Showed Improved Outcome Compared to Hyaluronic Acid and Physiotherapy for Massive Knee Chondral Defects: A Randomized Controlled Trial. Arthroscopy 2021; 37:2502-2517. [PMID: 34265388 DOI: 10.1016/j.arthro.2021.01.067] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 01/18/2021] [Accepted: 01/25/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study was to evaluate the safety and efficacy of intra-articular injections of autologous peripheral blood stem cells (PBSCs) plus hyaluronic acid (HA) after arthroscopic subchondral drilling into massive chondral defects of the knee joint and to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than HA plus physiotherapy. METHODS This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores. RESULTS At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures. CONCLUSIONS Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy. LEVEL OF EVIDENCE Level I, RCT.
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Chahla J, Gursoy S. Editorial Commentary: Peripheral Blood Stem Cells Mobilization Using Granulocyte Colony-Stimulating Factor for Articular Cartilage Injuries: Wake Them Up and Make Them Come to You! Arthroscopy 2021; 37:2518-2520. [PMID: 33745936 DOI: 10.1016/j.arthro.2021.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 02/02/2023]
Abstract
Articular cartilage injuries constitute a prevalent musculoskeletal problem in the general population. Restorative cartilage procedures are specifically challenging, as recapitulating hyaline cartilage can be difficult, thus compromising clinical outcomes. Progenitor cells for the treatment of articular cartilage injuries constitute a promising therapeutic method that has been increasing exponentially. Progenitor cells can be obtained from many different human tissues, such as bone marrow, adipose tissue, and muscle, as well as from peripheral blood after mobilizing stem cells from bone marrow with granulocyte colony-stimulating factor simulation. The minimally invasiveness, low complication rate, and efficacy of peripheral blood stem cells has gained significant attention and rapidly has become a promising source of progenitor cell delivery in the past decade.
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Yao RZ, Liu WQ, Sun LZ, Yu MD, Wang GL. Effectiveness of High Tibial Osteotomy with or without Other Procedures for Medial Compartment Osteoarthritis of Knee: An Update Meta-Analysis. J Knee Surg 2021; 34:952-961. [PMID: 31968360 DOI: 10.1055/s-0039-1700978] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
To improve the long-term outcomes of high tibial osteotomy (HTO) for gonarthritis, many cartilage repair procedures appeared, but their effects were controversial. To evaluate the efficacy of cartilage repair procedures during HTO for gonarthritis, we performed this update meta-analysis. We performed the system retrieval for clinical trials using various databases and then pooled the outcomes of the included studies. Fifteen studies were involved. The pooled results indicated that there were no significant differences in Kellgren and Lawrence (KL) scale (mean difference [MD] = 0.02, 95% confidence interval [CI] = -0.01 to 0.06, p = 0.24), the femorotibial angle (MD = 0.06, 95% CI = -0.04 to 0.16, p = 0.22), and magnetic resonance imaging (MRI) outcomes (MD = 12.53, 95% CI = -2.26 to 27.32, p = 0.10) of patients in experimental group than control. The subgroup analysis showed that the clinical outcomes of abrasion arthroplasty (AA) were worse than control group (standardized mean difference [SMD] -2.65, 95% CI = -3.67 to -1.63, p < 0.001), while mesenchymal stem cells (MSCs) injection improved the clinical outcomes (SMD = 2.37, 95% CI = 1.25-3.50, p < 0.001). There were significant differences between the two groups in arthroscopic (SMD = 1.38, 95% CI = 0.82-1.94, p < 0.001) and histologic results (relative risk [RR] = 1.77, 95% CI = 1.36-2.29, p < 0.001). The pain relief (MD = 0.17, 95% CI = -3.26 to 3.61, p = 0.92) and operative complications (RR = 1.42, 95% CI = 0.83-2.42; p = 0.19) of the two groups had no significant differences. Our analysis supports that concurrent cartilage repair procedures might improve arthroscopic and histologic outcomes, but they have no beneficial effect on clinical outcomes, radiograph, MRI, and pain relief. The concurrent procedures do not increase the risk of operative complication. Furthermore, MSC has some beneficial effects on clinical outcomes, while AA might play an opposite role.
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Affiliation(s)
- Ru-Zhan Yao
- Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China
| | - Wei-Qiang Liu
- Department of Spinal Surgery, Weifang People's Hospital, Weifang, China
| | - Liang-Zhi Sun
- Department of Spinal Surgery, Weifang People's Hospital, Weifang, China
| | - Ming-Dong Yu
- Department of Spinal Surgery, Weifang People's Hospital, Weifang, China
| | - Guang-Lin Wang
- Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China.,Department of Orthopaedics, The People's Hospital of Guang'an City, China
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12
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Papadopoulos KI, Turajane T. Erratum: Commentary: Autologous Peripheral Blood Stem Cells (PBSC) are Safe and Effective in Knee Osteoarthritis. Front Pharmacol 2021; 12:652738. [PMID: 33959019 PMCID: PMC8093874 DOI: 10.3389/fphar.2021.652738] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 02/22/2021] [Indexed: 02/05/2023] Open
Abstract
[This corrects the article DOI: 10.3389/fphar.2020.00404.].
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Affiliation(s)
| | - Thana Turajane
- Department of Orthopedics, Police General Hospital, Bangkok, Thailand
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13
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Dekker TJ, Aman ZS, DePhillipo NN, Dickens JF, Anz AW, LaPrade RF. Chondral Lesions of the Knee: An Evidence-Based Approach. J Bone Joint Surg Am 2021; 103:629-645. [PMID: 33470591 DOI: 10.2106/jbjs.20.01161] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
➤ Management of chondral lesions of the knee is challenging and requires assessment of several factors including the size and location of the lesion, limb alignment and rotation, and the physical and mental health of the individual patient. ➤ There are a multitude of options to address chondral pathologies of the knee that allow individualized treatment for the specific needs and demands of the patient. ➤ Osteochondral autograft transfer remains a durable and predictable graft option in smaller lesions (<2 cm2) in the young and active patient population. ➤ Both mid-term and long-term results for large chondral lesions (≥3 cm2) of the knee have demonstrated favorable results with the use of osteochondral allograft or matrix-associated chondrocyte implantation. ➤ Treatment options for small lesions (<2 cm2) include osteochondral autograft transfer and marrow stimulation and/or microfracture with biologic adjunct, while larger lesions (≥2 cm2) are typically treated with osteochondral allograft transplantation, particulated juvenile articular cartilage, or matrix-associated chondrocyte implantation. ➤ Emerging technologies, such as allograft scaffolds and cryopreserved allograft, are being explored for different graft sources to address complex knee chondral pathology; however, further study is needed.
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Affiliation(s)
- Travis J Dekker
- Division of Orthopaedics, Department of Surgery, Eglin Air Force Base, Eglin, Florida
| | - Zachary S Aman
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | | | - Jonathan F Dickens
- Division of Orthopaedics, Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Adam W Anz
- Andrews Research & Education Foundation, Gulf Breeze, Florida
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14
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Kim YS, Suh DS, Tak DH, Chung PK, Kwon YB, Kim TY, Koh YG. Factors Influencing Clinical and MRI Outcomes of Mesenchymal Stem Cell Implantation With Concomitant High Tibial Osteotomy for Varus Knee Osteoarthritis. Orthop J Sports Med 2021; 9:2325967120979987. [PMID: 33681398 PMCID: PMC7897834 DOI: 10.1177/2325967120979987] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 08/11/2020] [Indexed: 01/09/2023] Open
Abstract
Background Cartilage repair procedures using mesenchymal stem cells (MSCs) can provide superior cartilage regeneration in the medial compartment of the knee joint when high tibial osteotomy (HTO) is performed for varus knee osteoarthritis (OA). However, few studies have reported the factors influencing the outcomes of MSC implantation with concomitant HTO. Purpose To investigate the outcomes of MSC implantation with concomitant HTO and to identify the prognostic factors that are associated with the outcomes. Study Design Case series; Level of evidence, 4. Methods A total of 71 patients (75 knees) were retrospectively evaluated after MSC implantation with concomitant HTO. Clinical and radiological outcomes were evaluated, and magnetic resonance imaging (MRI) was used to assess cartilage regeneration. Statistical analyses were performed to determine the effect of different factors on clinical, radiographic, and MRI outcomes. Results Clinical and radiographic outcomes improved significantly from preoperatively to final follow-up (P < .001 for all), and overall cartilage regeneration was encouraging. Significant correlations were found between clinical and MRI outcomes. However, radiographic outcomes were not significantly correlated with clinical or MRI outcomes. Patient age and number of MSCs showed significant correlations with clinical and MRI outcomes. On multivariate analyses, patient age and number of MSCs showed high prognostic significance with poor clinical outcomes. Conclusion MSC implantation with concomitant HTO provided feasible cartilage regeneration and satisfactory clinical outcomes for patients with varus knee OA. Patient age and number of MSCs were important factors that influenced the clinical and MRI outcomes of MSC implantation with concomitant HTO for varus knee OA.
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Affiliation(s)
- Yong Sang Kim
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Dong Suk Suh
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Dae Hyun Tak
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Pill Ku Chung
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Yoo Beom Kwon
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Tae Yong Kim
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Yong Gon Koh
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
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15
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Song JS, Hong KT, Kong CG, Kim NM, Jung JY, Park HS, Kim YJ, Chang KB, Kim SJ. High tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells implantation for knee cartilage regeneration. World J Stem Cells 2020; 12:514-526. [PMID: 32742568 PMCID: PMC7360989 DOI: 10.4252/wjsc.v12.i6.514] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/24/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND High tibial osteotomy (HTO) is a well-established method for the treatment of medial compartment osteoarthritis of the knee with varus deformity. However, HTO alone cannot adequately repair the arthritic joint, necessitating cartilage regeneration therapy. Cartilage regeneration procedures with concomitant HTO are used to improve the clinical outcome in patients with varus deformity.
AIM To evaluate cartilage regeneration after implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with concomitant HTO.
METHODS Data for patients who underwent implantation of hUCB-MSCs with concomitant HTO were evaluated. The patients included in this study were over 40 years old, had a varus deformity of more than 5°, and a full-thickness International Cartilage Repair Society (ICRS) grade IV articular cartilage lesion of more than 4 cm2 in the medial compartment of the knee. All patients underwent second-look arthroscopy during hardware removal. Cartilage regeneration was evaluated macroscopically using the ICRS grading system in second-look arthroscopy. We also assessed the effects of patient characteristics, such as trochlear lesions, age, and lesion size, using patient medical records.
RESULTS A total of 125 patients were included in the study, with an average age of 58.3 ± 6.8 years (range: 43-74 years old); 95 (76%) were female and 30 (24%) were male. The average hip-knee-ankle (HKA) angle for measuring varus deformity was 7.6° ± 2.4° (range: 5.0-14.2°). In second-look arthroscopy, the status of medial femoral condyle (MFC) cartilage was as follows: 73 (58.4%) patients with ICRS grade I, 37 (29.6%) with ICRS grade II, and 15 (12%) with ICRS grade III. No patients were staged with ICRS grade IV. Additionally, the scores [except International Knee Documentation Committee (IKDC) at 1 year] of the ICRS grade I group improved more significantly than those of the ICRS grade II and III groups.
CONCLUSION Implantation of hUCB-MSCs with concomitant HTO is an effective treatment for patients with medial compartment osteoarthritis and varus deformity. Regeneration of cartilage improves the clinical outcomes for the patients.
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Affiliation(s)
- Jun-Seob Song
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul 06053, South Korea
| | - Ki-Taek Hong
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul 06053, South Korea
| | - Chae-Gwan Kong
- Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Uijeongbu-si 11765, South Korea
| | - Na-Min Kim
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul 06053, South Korea
| | - Jae-Yub Jung
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul 06053, South Korea
| | - Han-Soo Park
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul 06053, South Korea
| | - Young Ju Kim
- Department of Nursing Education & Administration, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Uijeongbu-si 11765, South Korea
| | - Ki Bong Chang
- Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Uijeongbu-si 11765, South Korea
| | - Seok Jung Kim
- Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Uijeongbu-si 11765, South Korea
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16
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Chen YR, Yan X, Yuan FZ, Ye J, Xu BB, Zhou ZX, Mao ZM, Guan J, Song YF, Sun ZW, Wang XJ, Chen ZY, Wang DY, Fan BS, Yang M, Song ST, Jiang D, Yu JK. The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review. Front Pharmacol 2020; 11:404. [PMID: 32308625 PMCID: PMC7145972 DOI: 10.3389/fphar.2020.00404] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 03/17/2020] [Indexed: 12/13/2022] Open
Abstract
Background Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. Methods PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. Results A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. Conclusion Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.
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Affiliation(s)
- You-Rong Chen
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Xin Yan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Fu-Zhen Yuan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jing Ye
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Bing-Bing Xu
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Zhu-Xing Zhou
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Zi-Mu Mao
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jian Guan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Yi-Fan Song
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Ze-Wen Sun
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.,School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Xin-Jie Wang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Ze-Yi Chen
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Ding-Yu Wang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Bao-Shi Fan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.,School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Meng Yang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.,School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Shi-Tang Song
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Dong Jiang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jia-Kuo Yu
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
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17
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Focal Chondral and Subchondral Bone Lesions of the Knee: Current Evidence for the Use of Biologic Treatment. OPER TECHN SPORT MED 2020. [DOI: 10.1016/j.otsm.2019.150716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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18
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Stammzelltherapie am Kniegelenk. ARTHROSKOPIE 2020. [DOI: 10.1007/s00142-020-00347-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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19
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Implantation of mesenchymal stem cells in combination with allogenic cartilage improves cartilage regeneration and clinical outcomes in patients with concomitant high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc 2020; 28:544-554. [PMID: 31549208 DOI: 10.1007/s00167-019-05729-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 09/16/2019] [Indexed: 01/22/2023]
Abstract
PURPOSE This study aimed to compare the clinical, radiological, and second-look arthroscopic outcomes of implanting mesenchymal stem cells (MSCs) alone and together with allogenic cartilage in patients treated with concomitant high tibial oteotomy (HTO) for varus knee osteoarthritis. METHODS Eighty patients treated with cartilage repair procedures and concomitant HTO were prospectively randomized into two groups: MSC implantation (MSC group), and MSC implantation with allogenic cartilage (MSC-AC group). Clinical outcomes were evaluated using the Lysholm Score and the Knee Injury and Osteoarthritis Outcome Score (KOOS) at preoperative and every follow-up visit. Radiological outcomes were evaluated by measuring the femorotibial angle and posterior tibial slope. During second-look arthroscopy, cartilage regeneration was evaluated according to the Kanamiya grade. RESULTS Clinical outcomes at the second-look arthroscopy (mean 12.5 months [MSC group] and 12.4 months [MSC-AC group]) improved significantly in both groups (P < 0.001 for all). Clinical outcomes from the second-look arthroscopy to the final follow-up (mean 27.3 months [MSC group] and 27.8 months [MSC-AC group]) improved further only in the MSC-AC group (P < 0.05 for all). Overall, the Kanamiya grades, which were significantly correlated with clinical outcomes, were significantly higher in the MSC-AC group than in the MSC group. Radiological outcomes at final follow-up revealed improved knee joint alignments relative to preoperative conditions but without significant correlation between clinical outcomes and Kanamiya grade in either group (n.s. for all). CONCLUSION Implantation of MSCs with allogenic cartilage is superior to implantation of MSCs alone in cartilage regeneration accompanied with better clinical outcomes. LEVEL OF EVIDENCE Therapeutic study, level II.
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20
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Freitag J, Norsworthy C, Wickham J, Shah K, Tenen A. High tibial osteotomy in combination with arthroscopic abrasion arthroplasty and autologous adipose-derived mesenchymal stem cell therapy in the treatment of advanced knee osteoarthritis. BMJ Case Rep 2019; 12:12/2/bcr-2018-228003. [PMID: 30733250 PMCID: PMC6381976 DOI: 10.1136/bcr-2018-228003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Osteoarthritis is a progressive and debilitating condition. An increasing number of total knee replacements are being performed under the age of 65. Improved understanding of the action of mesenchymal stem cells (MSC) has seen renewed interest in their role in cartilage repair. A 43-year-old man presented with grade IV medial compartment knee osteoarthritis. The patient underwent high tibial osteotomy (HTO) and arthroscopic abrasion arthroplasty in combination with adipose-derived MSC therapy. The patient reported improvement in pain and function as measured by validated outcome scores. Repeat MRI including T2 mapping techniques showed hyaline-like cartilage regeneration. This case highlights the potential benefit of surgical interventions including HTO in combination with MSC therapy in early-onset severe osteoarthritis. This technique may considerably delay or prevent the need for total knee replacement in young patients. Further controlled trials are needed to confirm the reproducibility of this outcome.
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Affiliation(s)
- Julien Freitag
- Charles Sturt University - Orange Campus, Orange, New South Wales, Australia.,Magellan Stem Cells, Box Hill North, Victoria, Australia.,Melbourne Stem Cell Centre, Box Hill North, Victoria, Australia
| | | | - James Wickham
- Charles Sturt University - Orange Campus, Orange, New South Wales, Australia
| | - Kiran Shah
- Magellan Stem Cells, Box Hill North, Victoria, Australia
| | - Abi Tenen
- Magellan Stem Cells, Box Hill North, Victoria, Australia.,Melbourne Stem Cell Centre, Box Hill North, Victoria, Australia.,Monash University, Clayton, Victoria, Australia
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21
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Christensen K, Cox B, Anz A. Emerging Orthobiologic Techniques and the Future. Clin Sports Med 2018; 38:143-161. [PMID: 30466719 DOI: 10.1016/j.csm.2018.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The future of orthopedic surgery appears to be intimately associated with the development of orthobiologics to facilitate healing and the treatment of multiple disease processes. The orthopedic community should understand developmental processes to ensure that products are adequately studied and the effects are fully known before widespread implementation in the clinical setting. Technologies that embrace this paradigm will impact the field the most.
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Affiliation(s)
- Kevin Christensen
- Andrews Institute, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA
| | - Benjamin Cox
- PLLC, 2890 Health Parkway, Mount Pleasant, MI 48858, USA
| | - Adam Anz
- Andrews Institute, Andrews Research and Education Foundation, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA.
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22
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No evidence for combining cartilage treatment and knee osteotomy in osteoarthritic joints: a systematic literature review. Knee Surg Sports Traumatol Arthrosc 2018; 26:3290-3299. [PMID: 29453488 DOI: 10.1007/s00167-018-4871-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 02/12/2018] [Indexed: 01/09/2023]
Abstract
PURPOSE To assess whether the combination of HTO and cartilage treatment produced an additional clinical benefit compared to HTO alone. The secondary aim was to identify if there was any difference among different cartilage procedures in terms of healing potential and clinical outcome. METHODS A systematic review of the literature was performed on PubMed database by three independent observers according to the following inclusion criteria: clinical reports of any level of evidence, written in the English language, with no time limitation, about HTO associated with cartilage surgical and injective treatment, including surveys reporting clinical, radiological, or second-look outcomes at any follow-up time. RESULTS The database search identified 1956 records: 21 studies were included for the final analysis, for a total of 1068 patients; 10 case series and 11 comparative studies. While overall good results were reported in the case series, the analysis of the comparative studies showed less uniform results. Among the eight studies investigating HTO with cartilage surgical procedures, improved tissue regeneration was found in 5/8 studies, whereas a clinical improvement was reported only in two studies. Three studies on HTO combination with injective treatment showed better tissue regeneration and clinical benefit. CONCLUSIONS Literature presents low-quality studies, with only few heterogeneous comparative papers. While surgical treatments targeting only the cartilage layer did not achieve clinical improvements, injective treatments targeting the overall joint environment showed promising findings. This prompts further research towards the development of treatments able to improve knee osteotomies outcomes. However, until new evidence will prove otherwise, there is no indication for a combined cartilage treatment in routine clinical practice. LEVEL OF EVIDENCE Level IV.
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23
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Kim YS, Koh YG. Comparative Matched-Pair Analysis of Open-Wedge High Tibial Osteotomy With Versus Without an Injection of Adipose-Derived Mesenchymal Stem Cells for Varus Knee Osteoarthritis: Clinical and Second-Look Arthroscopic Results. Am J Sports Med 2018; 46:2669-2677. [PMID: 30080423 DOI: 10.1177/0363546518785973] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND High tibial osteotomy (HTO) is reported to be an effective treatment for varus knee osteoarthritis (OA) by redistributing the load line within the knee joint. The cell-based tissue engineering approach using mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in knee OA. PURPOSE This study aimed to compare the clinical, radiological, and second-look arthroscopic outcomes of open-wedge HTO with versus without an MSC injection and to identify the association between cartilage regeneration and HTO outcomes. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS Among 271 patients treated with HTO for varus knee OA from September 2009 to April 2014, patients treated with HTO alone (conventional group; n = 50) were pair-matched with those who underwent HTO with an MSC injection (injection group; n = 50) based on sex, age, and lesion size. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) score and Lysholm score. Radiological outcomes evaluated were the femorotibial angle and posterior tibial slope. At second-look arthroscopic surgery, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. RESULTS At the time of second-look arthroscopic surgery (mean, 12.4 months [conventional group] and 12.7 months [injection group]), the mean IKDC and Lysholm scores in each group significantly improved: conventional group, from 38.4 ± 9.2 to 55.2 ± 15.0 and from 56.7 ± 12.2 to 79.6 ± 13.5, respectively; and injection group, from 36.5 ± 4.7 to 62.7 ± 14.1 and from 55.7 ± 11.9 to 80.6 ± 15.6, respectively ( P < .001 for all). Clinical outcomes at final follow-up (mean, 38.8 months [conventional group] and 37.2 months [injection group]) further improved from 62.7 ± 14.1 to 64.8 ± 13.4 (IKDC) and from 80.6 ± 15.6 to 84.7 ± 16.1 (Lysholm) ( P < .001 and P = .034, respectively) only in the injection group when compared with the values at second-look arthroscopic surgery. At final follow-up, there was a significant difference in the mean IKDC and Lysholm scores between groups ( P = .049 and P = .041, respectively). Overall ICRS grades, which significantly correlated with clinical outcomes, were better in the injection group than in the conventional group. Radiological outcomes at final follow-up showed improved knee joint alignment relative to patients' preoperative conditions but showed no significant correlation with clinical outcomes or ICRS grade in either group ( P > .05 for all). CONCLUSION The group that received an MSC injection scored better on the IKDC and Lysholm scales at final follow-up than the group that did not, although these differences were relatively small. When performing HTO for patients with varus knee OA, an MSC injection should be considered as an additional procedure for improved cartilage regeneration with better clinical outcomes.
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Affiliation(s)
- Yong Sang Kim
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
| | - Yong Gon Koh
- Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea
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24
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Park YB, Ha CW, Rhim JH, Lee HJ. Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell Populations Used and the Result of the Clinical Application of Each Entity. Am J Sports Med 2018; 46:2540-2552. [PMID: 29023156 DOI: 10.1177/0363546517729152] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Following successful preclinical studies, stem cell therapy is emerging as a candidate for the treatment of articular cartilage lesions. Because stem cell therapy for cartilage repair in humans is at an early phase, confusion and errors are found in the literature regarding use of the term stem cell therapy in this field. PURPOSE To provide an overview of the outcomes of cartilage repair, elucidating the various cell populations used, and thus reduce confusion with regard to using the term stem cell therapy. STUDY DESIGN Systematic review. METHODS The authors systematically reviewed any studies on clinical application of mesenchymal stem cells (MSCs) in human subjects. A comprehensive search was performed in MEDLINE, EMBASE, the Cochrane Library, CINAHL, Web of Science, and Scopus for human studies that evaluated articular cartilage repair with cell populations containing MSCs. These studies were classified as using bone marrow-derived MSCs, adipose tissue-derived MSCs, peripheral blood-derived MSCs, synovium-derived MSCs, and umbilical cord blood-derived MSCs according to the entity of cell population used. RESULTS Forty-six clinical studies were identified to focus on cartilage repair with MSCs: 20 studies with bone marrow-derived MSCs, 21 studies with adipose tissue-derived MSCs, 3 studies with peripheral blood-derived MSCs, 1 study with synovium-derived MSCs, and 1 study with umbilical cord blood-derived MSCs. All clinical studies reported that cartilage treated with MSCs showed favorable clinical outcomes in terms of clinical scores or cartilage repair evaluated by MRI. However, most studies were limited to case reports and case series. Among these 46 clinical studies, 18 studies erroneously referred to adipose tissue-derived stromal vascular fractions as "adipose-derived MSCs," 2 studies referred to peripheral blood-derived progenitor cells as "peripheral blood-derived MSCs," and 1 study referred to bone marrow aspirate concentrate as "bone marrow-derived MSCs." CONCLUSION Limited evidence is available regarding clinical benefit of stem cell therapy for articular cartilage repair. Because the literature contains substantial errors in describing the therapeutic cells used, researchers need to be alert and observant of proper terms, especially regarding whether the cells used were stem cells or cell populations containing a small portion of stem cells, to prevent confusion in understanding the results of a given stem cell-based therapy.
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Affiliation(s)
- Yong-Beom Park
- Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
| | - Chul-Won Ha
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.,Stem Cell & Regenerative Medicine Research Institute, Samsung Medical Center, Gangnam-gu, Seoul, Republic of Korea.,Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Gangnam-gu, Seoul, Republic of Korea
| | - Ji Heon Rhim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea
| | - Han-Jun Lee
- Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
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25
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Hsu AC, Tirico LEP, Lin AG, Pulido PA, Bugbee WD. Osteochondral Allograft Transplantation and Opening Wedge Tibial Osteotomy: Clinical Results of a Combined Single Procedure. Cartilage 2018; 9:248-254. [PMID: 28530120 PMCID: PMC6042037 DOI: 10.1177/1947603517710307] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Objective To evaluate the outcome of patients who have undergone simultaneous osteotomy and osteochondral allograft (OCA) transplantation. Our hypothesis is that use of high tibial osteotomy and fresh OCA in a combined procedure is safe and effective without increasing morbidity in comparison to OCA alone. Design A case series of 17 patients underwent tibial osteotomy and simultaneous OCA during a single surgery. Osteotomy was indicated when axial alignment was within the affected compartment. Patients had a minimum of 2 years of follow-up after surgery. The mean graft size was 8.7 cm2, with 82% located on the medial femoral condyle alone and 18% involving the medial femoral condyle and one or more other sites. Data collection included demographics, osteotomy correction, graft site(s) and area, and clinical evaluation. Failure was defined as conversion to arthroplasty. Results Two of 17 patients (12%) failed at a mean of 9.3 years. The remaining 15 patients (88%) had intact allografts with mean survival of 8.1 years (SD 3.3). Five patients (29%) had an additional procedure, all undergoing osteotomy hardware removal. Of those with surviving allografts, mean pain and function scores improved significantly from the preoperative to postoperative assessment and International Knee Documentation Committee total scores improved significantly from 40.9 ± 15.4 preoperative to 75.5 ± 24.0 at latest follow-up ( P = 0.003); 92% of patients were satisfied with the results of the surgery. No postoperative complications occurred. Conclusion Combining high tibial osteotomy and OCA in properly selected patients is safe and effective.
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Affiliation(s)
| | - Luis E. P. Tirico
- Shiley Center for Orthopaedic Research & Education, Scripps Clinic, La Jolla, CA, USA
| | - Abraham G. Lin
- Department of Orthopaedics, Kaiser Permanente, Downey, CA, USA
| | | | - William D. Bugbee
- Scripps Clinic Torrey Pines, La Jolla, CA, USA,William D. Bugbee, Division of Orthopaedic Surgery, Scripps Clinic, 10666 North Torrey Pines Road, MS116, La Jolla, CA 92037, USA.
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Abstract
Regenerative medicine seeks to harness the potential of cell biology for tissue replacement therapies, which will restore lost tissue functionality. Controlling and enhancing tissue healing is not just a matter of cells, but also of molecules and mechanical forces. We first describe the main biological technologies to boost musculoskeletal healing, including bone marrow and subcutaneous fat-derived regenerative products, as well as platelet-rich plasma and conditioned media. We provide some information describing possible mechanisms of action. We performed a literature search up to January 2016 searching for clinical outcomes following the use of cell therapies for sports conditions, tendons, and joints. The safety and efficacy of cell therapies for tendon conditions was examined in nine studies involving undifferentiated and differentiated (skin fibroblasts, tenocytes) cells. A total of 54 studies investigated the effects of mesenchymal stem-cell (MSC) products for joint conditions including anterior cruciate ligament, meniscus, and chondral lesions as well as osteoarthritis. In 22 studies, cellular products were injected intra-articularly, whereas in 32 studies MSC products were implanted during surgical/arthroscopic procedures. The heterogeneity of clinical conditions, cellular products, and approaches for delivery/implantation make comparability difficult. MSC products appear safe in the short- and mid-term, but studies with a long follow-up are scarce. Although the current number of randomized clinical studies is low, stem-cell products may have therapeutic potential. However, these regenerative technologies still need to be optimized.
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Affiliation(s)
- Isabel Andia
- Regenerative Medicine Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Pza Cruces 12, 48903, Barakaldo, Spain.
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, University of Salerno School of Medicine and Dentistry, Salerno, Italy.,Queen Mary University of London, Barts and the London School of Medicine and Dentistry Centre for Sports and Exercise Medicine, Mile End Hospital, 275 Bancroft Road, London, E1 4DG, England
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27
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The Application of Stem Cells from Different Tissues to Cartilage Repair. Stem Cells Int 2017; 2017:2761678. [PMID: 29375622 PMCID: PMC5742463 DOI: 10.1155/2017/2761678] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 10/24/2017] [Indexed: 12/15/2022] Open
Abstract
The degeneration of articular cartilage represents an ongoing challenge at the clinical and basic level. Tissue engineering and regenerative medicine using stem/progenitor cells have emerged as valid alternatives to classical reparative techniques. This review offers a brief introduction and overview of the field, highlighting a number of tissue sources for stem/progenitor cell populations. Emphasis is given to recent developments in both clinical and basic sciences. The relative strengths and weaknesses of each tissue type are discussed.
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Turajane T, Chaveewanakorn U, Fongsarun W, Aojanepong J, Papadopoulos KI. Avoidance of Total Knee Arthroplasty in Early Osteoarthritis of the Knee with Intra-Articular Implantation of Autologous Activated Peripheral Blood Stem Cells versus Hyaluronic Acid: A Randomized Controlled Trial with Differential Effects of Growth Factor Addition. Stem Cells Int 2017; 2017:8925132. [PMID: 29056974 PMCID: PMC5625803 DOI: 10.1155/2017/8925132] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 07/25/2017] [Accepted: 08/24/2017] [Indexed: 02/08/2023] Open
Abstract
In this randomized controlled trial, in early osteoarthritis (OA) that failed conservative intervention, the need for total knee arthroplasty (TKA) and WOMAC scores were evaluated, following a combination of arthroscopic microdrilling mesenchymal cell stimulation (MCS) and repeated intra-articular (IA) autologous activated peripheral blood stem cells (AAPBSCs) with growth factor addition (GFA) and hyaluronic acid (HA) versus IA-HA alone. Leukapheresis-harvested AAPBSCs were administered as three weekly IA injections combined with HA and GFA (platelet-rich plasma [PRP] and granulocyte colony-stimulating factor [hG-CSF]) and MCS in group 1 and in group 2 but without hG-CSF while group 3 received IA-HA alone. Each group of 20 patients was evaluated at baseline and at 1, 6, and, 12 months. At 12 months, all patients in the AAPBSC groups were surgical intervention free compared to three patients needing TKA in group 3 (p < 0.033). Total WOMAC scores showed statistically significant improvements at 6 and 12 months for the AAPBSC groups versus controls. There were no notable adverse events. We have shown avoidance of TKA in the AAPBSC groups at 12 months and potent, early, and sustained symptom alleviation through GFA versus HA alone. Differential effects of hG-CSF were noted with an earlier onset of symptom alleviation throughout.
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Affiliation(s)
- Thana Turajane
- Department of Orthopedic Surgery, Police General Hospital, Bangkok, Thailand
| | | | | | - Jongjate Aojanepong
- Department of Gynecology and Obstetrics, Police General Hospital, Bangkok, Thailand
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29
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Zeineddine HA, Frush TJ, Saleh ZM, El-Othmani MM, Saleh KJ. Applications of Tissue Engineering in Joint Arthroplasty: Current Concepts Update. Orthop Clin North Am 2017; 48:275-288. [PMID: 28577777 DOI: 10.1016/j.ocl.2017.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Research in tissue engineering has undoubtedly achieved significant milestones in recent years. Although it is being applied in several disciplines, tissue engineering's application is particularly advanced in orthopedic surgery and in degenerative joint diseases. The literature is full of remarkable findings and trials using tissue engineering in articular cartilage disease. With the vast and expanding knowledge, and with the variety of techniques available at hand, the authors aimed to review the current concepts and advances in the use of cell sources in articular cartilage tissue engineering.
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Affiliation(s)
- Hussein A Zeineddine
- Department of Surgery, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA
| | - Todd J Frush
- Department of Orthopaedics and Sports Medicine, Detroit Medical Center, University Health Center (UHC) 9B, 4201 Saint Antoine Street, Detroit, MI 48201-2153, USA
| | - Zeina M Saleh
- Department of Surgery, American University of Beirut Medical Center, Bliss Street, Riad El-Solh, Beirut 11072020, Lebanon
| | - Mouhanad M El-Othmani
- Department of Orthopaedics and Sports Medicine, Musculoskeletal Institute of Excellence, Detroit Medical Center, University Health Center (UHC) 9B, 4201 Saint Antoine Street, Detroit, MI 48201-2153, USA
| | - Khaled J Saleh
- Department of Orthopaedics and Sports Medicine, Detroit Medical Center, University Health Center (UHC) 9B, 4201 Saint Antoine Street, Detroit, MI 48201-2153, USA.
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30
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Kim KI, Seo MC, Song SJ, Bae DK, Kim DH, Lee SH. Change of Chondral Lesions and Predictive Factors After Medial Open-Wedge High Tibial Osteotomy With a Locked Plate System. Am J Sports Med 2017; 45:1615-1621. [PMID: 28291955 DOI: 10.1177/0363546517694864] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although cartilage regeneration after medial open-wedge high tibial osteotomy (HTO) has been described, there is a paucity of reports regarding which factors influence cartilage regeneration. PURPOSE To document whether cartilage regeneration occurs in the previously degenerated medial compartment of arthritic knees after medial open-wedge HTO without concomitant cartilage procedures and to assess which predictive factors influence regeneration after HTO. STUDY DESIGN Case series; Level of evidence, 4 Methods: From February 2008 to January 2014, 104 consecutive knees were enrolled retrospectively that received medial open-wedge HTO with a medial locked plate system without any additional cartilage regeneration procedures and were followed by second-look arthroscopy for plate removal 2 years after surgery. The mean ± SD age at the time of index HTO was 56.3 ± 5.4 years. Cartilage status was graded at the time of initial HTO and second-look arthroscopy according to the International Cartilage Repair Society grading system, and regenerated articular cartilage was classified by the macroscopic staging system of Koshino et al at the time of second-look arthroscopy. Variables evaluated for possible association with regeneration of articular cartilage included age, sex, body mass index (BMI), American Knee Society score, mechanical tibiofemoral angle, medial proximal tibial angle, amount of correction angle, and degree of arthritis. RESULTS Per the International Cartilage Repair Society grading system, the lesions in the medial femoral condyle and the medial tibial plateau were improved in 54 knees (51.9%) and 36 knees (34.6%), respectively, at the time of second-look arthroscopy. According to the macroscopic grading system, partial and total regeneration of articular cartilage in the medial femoral condyle and the medial tibial plateau was observed in 75 knees (72%) and 57 knees (55%), respectively. Based on univariable logistic regression tests, regeneration of articular cartilage was associated with a smaller mean preoperative varus mechanical tibiofemoral angle (odds ratio [OR], 0.7; P = .023) and lower BMI (OR, 0.8; P = .026) for the medial femoral condyle and younger age (OR, 0.9; P = .048) and a larger mean correction angle (OR, 1.1; P = .023) for the medial tibial plateau. The mean preoperative knee and function scores were significantly improved at the last follow-up, but no correlation was found between the clinical outcomes and cartilage regeneration. Multiple logistic regression analysis for regeneration of articular cartilage showed lower BMI (OR, 0.7; P = .015) to be a significant predictor for the medial femoral condyle. CONCLUSION Regeneration of degenerated articular cartilage in the medial compartment can be expected while correcting a varus deformity in arthritic knees after medial open-wedge HTO with a locked plate system without any additional cartilage regeneration procedures. Moreover, we suggest that medial open-wedge HTO in the medial arthritic knee with varus malalignment should be highly successful in terms of cartilage regeneration, especially for lower BMI patients.
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Affiliation(s)
- Kang-Il Kim
- Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Korea.,Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Min-Chul Seo
- Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Sang-Jun Song
- Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dae-Kyung Bae
- Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Duk-Hyun Kim
- Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Sang Hak Lee
- Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Korea.,Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University, Seoul, Korea
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31
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Rodriguez-Fontan F, Piuzzi NS, Chahla J, Payne KA, LaPrade RF, Muschler GF, Pascual-Garrido C. Stem and Progenitor Cells for Cartilage Repair: Source, Safety, Evidence, and Efficacy. OPER TECHN SPORT MED 2017. [DOI: 10.1053/j.otsm.2016.12.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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32
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Thambiah MD, Tan MKL, Hui JHP. Role of High Tibial Osteotomy in Cartilage Regeneration - Is Correction of Malalignment Mandatory for Success? Indian J Orthop 2017; 51:588-599. [PMID: 28966382 PMCID: PMC5609380 DOI: 10.4103/ortho.ijortho_260_17] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Malalignment of the knee can cause debilitating symptoms such as pain, resulting in a decline in function and mobility. Surgical options that exist to address this problem include realignment osteotomies and joint replacements. Realignment osteotomies are the more appropriate options in certain patient populations, especially with regard to age and level of activity. Since a high tibial osteotomy (HTO) was first used to manage malalignment of the knee and osteoarthritis, different techniques involving the use of specialized implants have been developed and further refined to good effect. There has also since been much research into the field of cartilage restoration techniques, both as a standalone treatment option and as an adjunct to a realignment osteotomy. This review attempts to detail the origin and the evolution of HTO, particularly in regard to combining this tried and tested procedure with adjunct cartilage restoration techniques, and the overall patient outcomes. A literature search on PubMed was performed, and articles pertaining to the outcomes of the use of an HTO and cartilage restoration techniques were reviewed. The literature in this field indicates good outcomes in terms of objective measurements of cartilage regeneration (such as arthroscopic visualization and magnetic resonance imaging evaluation) and subjective patient outcome scoring systems (such as the International Knee Documentation Committee and Lysholm scores) with a realignment osteotomy alone, and studies have shown that patient outcomes can be further improved with the use of a cartilage restoration procedure as an adjunct.
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Affiliation(s)
- Matthew Dhanaraj Thambiah
- National University of Singapore and University Orthopaedics, Hand and Reconstructive Microsurgery Cluster, National University Hospital, Singapore
| | - Melvin K L Tan
- National University of Singapore and University Orthopaedics, Hand and Reconstructive Microsurgery Cluster, National University Hospital, Singapore
| | - James H P Hui
- National University of Singapore and University Orthopaedics, Hand and Reconstructive Microsurgery Cluster, National University Hospital, Singapore,Address for correspondence: Prof. James H P Hui, National University of Singapore and University Orthopaedics, Hand and Reconstructive Microsurgery Cluster, National University Hospital, Level 11 NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore. E-mail:
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33
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Abstract
Background and purpose - Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation - Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints.
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Affiliation(s)
- Mats Brittberg
- Cartilage Research Unit, University of Gothenburg, Region Halland Orthopaedics, Kungsbacka Hospital, Kungsbacka, Sweden,Correspondence:
| | - Andreas H Gomoll
- Harvard Medical School, Cartilage Repair Center, Brigham and Women’s Hospital, Boston, MA
| | - José A Canseco
- Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA
| | - Jack Far
- Indiana University School of Medicine, OrthoIndy Cartilage Restoration Center, Indianapolis, IN, USA
| | - Martin Lind
- Division of Sports Traumatology, Department of Orthopedics, Aarhus University Hospital, Århus, Denmark
| | - James Hui
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University Singapore, Singapore
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34
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Akpancar S, Tatar O, Turgut H, Akyildiz F, Ekinci S. The Current Perspectives of Stem Cell Therapy in Orthopedic Surgery. ARCHIVES OF TRAUMA RESEARCH 2016; 5:e37976. [PMID: 28144608 PMCID: PMC5253188 DOI: 10.5812/atr.37976] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 06/16/2016] [Accepted: 06/23/2016] [Indexed: 12/26/2022]
Abstract
CONTEXT Musculoskeletal injuries may be painful, troublesome, life limiting and also one of the global health problems. There has been considerable amount of interest during the past two decades to stem cells and tissue engineering techniques in orthopedic surgery, especially to manage special and compulsive injuries within the musculoskeletal system. EVIDENCE ACQUISITION The aim of this study was to present a literature review regarding the most recent progress in stem cell procedures and current indications in orthopedics clinical care practice. The Medline and PubMed library databases were searched for the articles related with stem cell procedures in the field of orthopedic surgery and additionally the reference list of each article was also included to provide a comprehensive evaluation. RESULTS Various sources of stem cells have been studied for orthopedics clinical care practice. Stem cell therapy has successfully used for major orthopedic procedures in terms of bone-joint injuries (fractures-bone defects, nonunion, and spinal injuries), osteoarthritis-cartilage defects, ligament-tendon injuries, femoral head osteonecrosis and osteogenesis imperfecta. Stem cells have also used in bone tissue engineering in combining with the scaffolds and provided faster and better healing of tissues. CONCLUSIONS Large amounts of preclinical studies have been made of stem cells and there is an increasing interest to perform these studies within the human population but preclinical studies are insufficient; therefore, much more and efficient studies should be conducted to evaluate the efficacy and safety of stem cells.
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Affiliation(s)
- Serkan Akpancar
- Department of Orthopedic Surgery, Gulhane Military Hospital, Ankara, Turkey
- Corresponding author: Serkan Akpancar, Department of Orthopedic Surgery, Gulhane Military Medicine Academy, Ankara, Turkey. Tel: +90-5443229700, Fax: +90-3124045500, E-mail:
| | - Oner Tatar
- Department of Orthopedic Surgery, Air Force Academy Kasımpaşa Military Hospital, Istanbul, Turkey
| | - Hasan Turgut
- Department of Orthopedic Surgery, Bursa Military Hospital, Bursa, Turkey
| | - Faruk Akyildiz
- Department of Orthopedic Surgery, Gulhane Military Hospital, Ankara, Turkey
| | - Safak Ekinci
- Department of Orthopedic Surgery, Agri Military Hospital, Agri, Turkey
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35
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Concepts in regenerative medicine: Past, present, and future in articular cartilage treatment. J Clin Orthop Trauma 2016; 7:137-44. [PMID: 27489407 PMCID: PMC4949414 DOI: 10.1016/j.jcot.2016.05.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 05/16/2016] [Indexed: 01/01/2023] Open
Abstract
Regenerative medicine is emerging with great interest and hope from patients, industry, academia, and medical professionals. Cartilage regeneration, restoration, or repair is one of the prime targets that remains largely unsolved, and many believe that regenerative medicine can possibly deliver solutions that can be widely used to address the current gap(s) in treatment. In the United States, Europe, Australia, and India the regulation of regenerative based treatments has become a big debate. Although the rules and regulations remain unclear, clinicians that are interested should carry-on with the best available guidelines to ensure safety and compliance during delivery in clinical practice to avoid regulatory infraction. Many have made significant investment of time, resources, and facilities in recent years to provide new regenerative treatment options and advance medical care for patients. Instead of reinventing the wheel, it would be more efficient to adopt currently accepted standards and nomenclature borrowed from transplantation science, and cord blood storage industries. The purposes of this article are to provide some historical background to the field of regenerative medicine as it applies to cartilage, and how this field has developed. This will be followed by a separate discussion on regulatory oversight and input and how it has influenced access to care. Furthermore, we discuss current clinical techniques and progress, and ways to deliver these treatments to patients safely, effectively, and in a cost sensitive manner, concluding with an overview of some of the promising regenerative techniques specific to cartilage.
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36
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Abstract
Among the surgical options for large full-thickness chondral injuries, cell-based therapy has been practiced and its satisfactory outcomes have been reported. One area that appears promising is cell-based therapies utilizing stem cells. Various tissues within the human body contain mesenchymal stem cells (MSCs) from where these can be harvested. These include bone marrow, adipose, synovium, peripheral blood, and umbilical cord. In this article, both preclinical animal studies and clinical studies dealing with the use of MSCs for cartilage repair of the knee are reviewed. Majority of the clinical papers have shown promising results; however, there are a limited number of studies of high evidence level. Clinical significance of the stem cell therapy as compared to other surgical options as well as optimization of the procedure in terms of cell type and delivery method is still to be determined.
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Affiliation(s)
- Shinichi Yoshiya
- Department of Orthopaedic Surgery, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Aman Dhawan
- Sports Medicine, Penn State Hershey Bone and Joint Institute, Hershey, PA, 17033-0850, USA.
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