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Migliorini F, Pilone M, Ascani J, Schäfer L, Jeyaraman M, Maffulli N. Management of knee osteoarthritis using bone marrow aspirate concentrate: a systematic review. Br Med Bull 2025; 153:ldae016. [PMID: 39506910 DOI: 10.1093/bmb/ldae016] [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: 01/11/2024] [Revised: 08/20/2024] [Accepted: 10/17/2024] [Indexed: 11/08/2024]
Abstract
INTRODUCTION Knee osteoarthritis (OA) is a common degenerative joint condition and a major cause of disability in the general population. SOURCE OF DATA Recent published literature identified from PubMed, EMBASE, Google Scholar, and Scopus. AREAS OF AGREEMENT Orthobiological therapies try to regenerate articular cartilage and stop the progression of the degenerative lesion. Intra-articular injections of biological derivates have been increasingly used in the last decade. AREAS OF CONTROVERSY The indications for the use of bone marrow aspirate concentrate (BMAC) are still unclear. GROWING POINTS We systematically reviewed the current literature on BMAC in the management of knee OA, giving an update on the current indications for the selection of the ideal patient and the preparations and efficacy of BMAC compared to other biological alternatives. AREAS TIMELY FOR DEVELOPING RESEARCH BMAC is a valuable source of mesenchymal stem cells, offering potential benefits in attenuating the inflammatory pathway associated with knee OA. Intra-articular injection of BMAC has shown effectiveness in clinical trials improving functional outcomes of knee OA patients. The superiority of BMAC over other orthobiological treatments cannot be assessed because of conflicting results.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic and Trauma Surgery, Academic Hospital of Bolzano (SABES-ASDAA), Via Lorenz Böhler 5, 39100, Bolzano, Italy
- Department of Life Sciences, Health, and Health Professions, Link Campus University, Via del Casale di San Pio V, 00165 Rome, Italy
| | - Marco Pilone
- Residency Program in Orthopedics and Traumatology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Jacopo Ascani
- Department of Trauma and Orthopaedic Surgery, Faculty of Medicine and Psychology, University "La Sapienza" of Rome, Via di Grottarossa 1035, 00189 Roma, Italy
| | - Luise Schäfer
- Department of Orthopaedic and Trauma Surgery, Academic Hospital of Bolzano (SABES-ASDAA), Via Lorenz Böhler 5, 39100, Bolzano, Italy
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Poonamallee High Rd, Velappanchavadi, Chennai 600077, Tamil Nadu, India
| | - Nicola Maffulli
- Department of Trauma and Orthopaedic Surgery, Faculty of Medicine and Psychology, University "La Sapienza" of Rome, Via di Grottarossa 1035, 00189 Roma, Italy
- School of Pharmacy and Bioengineering, Keele University Faculty of Medicine, Stoke on Trent ST4 7QB, United Kingdom
- 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, E1 4DG London, UK
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Sin A, Hollabaugh W, Porras L. Narrative review and call to action on reporting and representation in orthobiologics research for knee osteoarthritis. PM R 2025; 17:88-95. [PMID: 38970438 PMCID: PMC11733843 DOI: 10.1002/pmrj.13214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 07/08/2024]
Abstract
Osteoarthritis affects a significant portion of U.S. adults, and knee osteoarthritis contributes to 80% of disease burden. Previous data have shown that non-White patient populations often report worse symptoms and less favorable outcomes following arthroplasty, a definitive treatment for knee osteoarthritis. There is a lack of demographics data on race/ethnicity, as well as socioeconomic status (SES) and social determinants of health (SDOH), in knee osteoarthritis treatment guidelines and knee arthroplasty research. In addition, there is underrepresentation of non-White patient populations in the existing treatment guidelines for knee osteoarthritis. Over the past decade, orthobiologics have emerged as an alternative to surgical intervention. Our hypothesis is that there would be a similar lack of reporting of demographics data and underrepresentation of non-White populations in studies pertaining to orthobiologics, including evaluating differences in outcomes. This study reviewed U.S.-based research in orthobiologics as a treatment option for knee osteoarthritis. We identified a lack of demographics reporting in terms of race/ethnicity, and none of the studies reported SES or SDOH. Non-White populations were underrepresented; White patients contributed to 80% or more of all study populations that reported race/ethnicity. None studied the correlation between symptoms and outcome measures, and the race/ethnicity, SES, and SDOH of the patients. Based on a review of existing literature, we strongly advocate for ongoing research encompassing patients of all races/ethnicities, SES, and SDOH, and an exploration into potential variations in symptoms and outcomes among distinct population subgroups. Furthermore, SES barriers may influence health care delivery on orthobiologics for disadvantaged populations.
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Affiliation(s)
- Alexander Sin
- Division of Sports Medicine, Department of Orthopaedic SurgeryVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - William Hollabaugh
- Division of Sports Medicine, Department of Orthopaedic SurgeryVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Lauren Porras
- Division of Sports Medicine, Department of Orthopaedic SurgeryVanderbilt University Medical CenterNashvilleTennesseeUSA
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Lee HJ, Hossain R, Baek CH, Lee CJ, Hwang SC. Intra-Articular Injection of Stem Cells for the Regeneration of Knee Joint Cartilage: a Therapeutic Option for Knee Osteoarthritis - a Narrative Review. Biomol Ther (Seoul) 2025; 33:86-94. [PMID: 39632656 PMCID: PMC11704397 DOI: 10.4062/biomolther.2024.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/22/2024] [Accepted: 10/30/2024] [Indexed: 12/07/2024] Open
Abstract
Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.
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Affiliation(s)
- Hyun Jae Lee
- Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University, Seoul 01795, Republic of Korea
| | - Rajib Hossain
- Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
- Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Chang-Heon Baek
- Department of Orthopaedic Surgery and Institute of Health Sciences, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea
| | - Choong Jae Lee
- Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
- Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Sun-Chul Hwang
- Department of Orthopaedic Surgery and Institute of Health Sciences, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea
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Alazzeh MS, Naseh HAM, Vasiliadis A, Laupheimer M, Kalifis G, Al‐Dolaymi A, Macchiarola L, Marín Fermín T. Platelet-rich plasma intra-articular knee injections from open preparation techniques do not pose a higher risk of joint infection: A systematic review of 91 randomized controlled trials and 5914 injections. J Exp Orthop 2024; 11:e70002. [PMID: 39318712 PMCID: PMC11420304 DOI: 10.1002/jeo2.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/01/2024] [Accepted: 05/08/2024] [Indexed: 09/26/2024] Open
Abstract
Purpose To compare the infection rate of intraarticular platelet-rich plasma (PRP) knee injections between open and closed techniques in randomized controlled trials (RCTs) published in the last decade. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, Scopus and Virtual Health Library were accessed in October 2022 using the terms 'platelet-rich plasma', 'PRP', 'knee' and 'tibiofemoral' alone and in combination with Boolean operators AND/OR. RCTs published during the last 10 years evaluating PRP intra-articular knee injections were considered eligible. Studies were excluded if the kit/preparation technique was not described. Data were presented using individual studies' absolute values, totals, and pooled percentages. Publication bias was assessed using the ROBIS tool. Results Ninety-one studies met the predetermined eligibility criteria. Forty-one implemented a closed technique, while 50 were open. All studies implementing a closed technique disclosed their commercial kits. Only 16 studies (17.58%) failed to report joint infections. Among the studies reporting joint infections as outcomes, 30 implemented a closed technique with 1195 patients, 1921 intra-articular knee injections and 95.44% of patient follow-up. On the other hand, 45 of them implemented an open technique with 2290 patients, 3993 intra-articular knee injections and 97.07% of patient follow-up. No patient had a joint infection among the included studies. Thirty-three studies prepared their PRP in controlled environments (36.26%). Most studies did not report where the preparation occurred (48.35%). Only twelve studies disclosed using laminar flow during preparation (13.19%). The infection rate for both techniques was 0 per 1000 knee injections. Conclusion Open PRP preparation techniques do not pose a higher risk of joint infection and can lower manufacturing costs when appropriate facilities are available. However, PRP preparation setting and laminar flow implementation data are deficient, and minimal requirements for good manufacturing practices demand further studies while adhering to local and regional regulations. Level of Evidence Level I, systematic review of RCTs.
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Affiliation(s)
| | | | - Angelo Vasiliadis
- Department of Orthopaedic Surgery, Sports Trauma UnitSt. Luke's HospitalThessalonikiGreece
| | - Markus Laupheimer
- SwisssportscareZurichSwitzerland
- The Centre for Sports & Exercise MedicineQueen Mary University of LondonLondonUK
| | - Georgios Kalifis
- Thessaloniki Minimally Invasive Surgery (TheMIS) Orthopaedic CenterSt. Luke's HospitalThessalonikiGreece
| | | | - Luca Macchiarola
- Ospedale Casa Sollievo della SofferenzaSan Giovanni RotondoFoggiaItaly
| | - Theodorakys Marín Fermín
- Thessaloniki Minimally Invasive Surgery (TheMIS) Orthopaedic CenterSt. Luke's HospitalThessalonikiGreece
- Centro Médico Profesional Las MercedesCaracasVenezuela
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Muthu S, Patil SC, Jeyaraman N, Jeyaraman M, Gangadaran P, Rajendran RL, Oh EJ, Khanna M, Chung HY, Ahn BC. Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis: A meta-analysis. World J Orthop 2023; 14:23-41. [PMID: 36686284 PMCID: PMC9850793 DOI: 10.5312/wjo.v14.i1.23] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/20/2022] [Accepted: 12/14/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population.
AIM To analyze and compare the efficacy and safety of bone-marrow-derived mesenchymal stromal cells (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) in knee OA management from published randomized controlled trials (RCTs).
METHODS Independent and duplicate electronic database searches were performed, including PubMed, EMBASE, Web of Science, and Cochrane Library, until August 2021 for RCTs that analyzed the efficacy and safety of AD-MSCs and BM-MSCs in the management of knee OA. The visual analog scale (VAS) score for pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Tegner score, magnetic resonance observation of cartilage repair tissue score, knee osteoarthritis outcome score (KOOS), and adverse events were analyzed. Analysis was performed on the R-platform using OpenMeta (Analyst) software. Twenty-one studies, involving 936 patients, were included. Only one study compared the two MSC sources without patient randomization; hence, the results of all included studies from both sources were pooled, and a comparative critical analysis was performed.
RESULTS At six months, both AD-MSCs and BM-MSCs showed significant VAS improvement (P = 0.015, P = 0.012); this was inconsistent at 1 year for BM-MSCs (P < 0.001, P = 0.539), and AD-MSCs outperformed BM-MSCs compared to controls in measures such as WOMAC (P < 0.001, P = 0.541), Lysholm scores (P = 0.006; P = 0.933), and KOOS (P = 0.002; P = 0.012). BM-MSC-related procedures caused significant adverse events (P = 0.003) compared to AD-MSCs (P = 0.673).
CONCLUSION Adipose tissue is superior to bone marrow because of its safety and consistent efficacy in improving pain and functional outcomes. Future trials are urgently warranted to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.
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Affiliation(s)
- Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Indian Stem Cell Study Group Association, Lucknow 226001, Uttar Pradesh, India
| | - Sandesh C Patil
- Department of Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226012, Uttar Pradesh, India
| | - Naveen Jeyaraman
- Indian Stem Cell Study Group Association, Lucknow 226001, Uttar Pradesh, India
- Department of Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226012, Uttar Pradesh, India
| | - Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Indian Stem Cell Study Group Association, Lucknow 226001, Uttar Pradesh, India
- Department of Orthopaedics, ACS Medical College & Hospital, Dr MGR Educational and Research Institute, Chennai 600056, Tamil Nadu, India
| | - Prakash Gangadaran
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Eun Jung Oh
- Department of Plastic and Reconstructive Surgery, CMRI, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea
| | - Manish Khanna
- Indian Stem Cell Study Group Association, Lucknow 226001, Uttar Pradesh, India
| | - Ho Yun Chung
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Plastic and Reconstructive Surgery, CMRI, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea
- Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Byeong-Cheol Ahn
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
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Jeyaraman M, Muthu S, Nischith DS, Jeyaraman N, Nallakumarasamy A, Khanna M. PRISMA-Compliant Meta-Analysis of Randomized Controlled Trials on Osteoarthritis of Knee Managed with Allogeneic vs Autologous MSCs: Efficacy and Safety Analysis. Indian J Orthop 2022; 56:2042-2059. [PMID: 36507199 PMCID: PMC9705690 DOI: 10.1007/s43465-022-00751-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 09/06/2022] [Indexed: 02/08/2023]
Abstract
Study Design Meta-analysis. Objectives Our objective is to review the randomized controlled trials (RCTs) that have been conducted previously on the topic of osteoarthritis of the knee to assess and compare the efficacy and safety of autologous and allogeneic sources of mesenchymal stromal cells (MSCs) in the treatment of osteoarthritis. Materials and methods We searched the electronic databases PubMed, Embase, Web of Science, and the Cochrane Library until August 2021 for randomised controlled trials (RCTs) analysing the efficacy and safety of autologous and allogeneic sources of MSCs in the management of knee osteoarthritis. These searches were conducted independently and in duplicate. The outcomes that were taken into consideration for analysis were the visual analogue score (VAS) for pain, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), the Lysholm score, and adverse events. The OpenMeta [Analyst] software was utilised to carry out the analysis in the R platform. Results In total, 21 studies with a total of 936 patients were considered for this analysis. Because none of the studies made a direct comparison of the autologous and allogeneic sources of MSCs, we pooled the results of all of the included studies of both sources and made a comparative analysis of how the two types of MSCs fared in their respective applications. Although both allogeneic and autologous sources of MSCs demonstrated significantly better VAS improvement after 6 months (p = 0.006, p = 0.001), this trend was not maintained after 1 year for the allogeneic source (p = 0.171, p = 0.027). When compared to their respective controls based on WOMAC scores after 1 year, autologous sources (p = 0.016) of MSCs performed better than allogeneic sources (p = 0.186).A similar response was noted between the sources at 2 years in their Lysholm scores (p = 0.682, p = 0.017), respectively. Moreover, allogeneic sources (p = 0.039) of MSCs produced significant adverse events than autologous sources (p = 0.556) compared to their controls. Conclusion Our analysis of literature showed that autologous sources of MSCs stand superior to allogeneic sources of MSC with regard to their consistent efficacy for pain, functional outcomes, and safety. However, we strongly recommend that further studies be conducted that are of a high enough quality to validate our findings and reach a consensus on the best source of MSCs for use in cellular therapy treatments for knee osteoarthritis. Supplementary Information The online version contains supplementary material available at 10.1007/s43465-022-00751-z.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai, Tamil Nadu India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Uttar Pradesh, Greater Noida, India
- Indian Stem Cell Study Group (ISCSG) Association, Uttar Pradesh, Lucknow, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Uttar Pradesh, Greater Noida, India
- Indian Stem Cell Study Group (ISCSG) Association, Uttar Pradesh, Lucknow, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu India
| | - D. S. Nischith
- Indian Stem Cell Study Group (ISCSG) Association, Uttar Pradesh, Lucknow, India
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Uttar Pradesh, Lucknow, India
| | - Naveen Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Uttar Pradesh, Lucknow, India
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Uttar Pradesh, Lucknow, India
- Fellow in Joint Replacement, Atlas Hospitals, Tiruchirappalli, Tamil Nadu India
| | - Arulkumar Nallakumarasamy
- Indian Stem Cell Study Group (ISCSG) Association, Uttar Pradesh, Lucknow, India
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Uttar Pradesh, Lucknow, India
- Department of Orthopaedics, All India Institute of Medical Sciences, Bhubaneswar, Odisha India
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Uttar Pradesh, Lucknow, India
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Pasculli RM, Kenyon CD, Berrigan WA, Mautner K, Hammond K, Jayaram P. Mesenchymal stem cells for subchondral bone marrow lesions: From bench to bedside. Bone Rep 2022; 17:101630. [PMID: 36310763 PMCID: PMC9615138 DOI: 10.1016/j.bonr.2022.101630] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 10/04/2022] [Accepted: 10/19/2022] [Indexed: 11/21/2022] Open
Abstract
Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.
Common BMLs include osteoarthritis, osteochondral defects, and avascular necrosis. Patients with knee osteoarthritis treated with MSCs show improved pain and function. MSCs used as subchondral injection or surgical augmentation in osteochondral defects Improved outcomes of early hip avascular necrosis after core decompression with MSCs Additional preclinical and clinical evidence of MSCs as treatment for BMLs is needed.
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Jeyaraman M, Shivaraj B, Bingi SK, Ranjan R, Muthu S, Khanna M. Does vehicle-based delivery of mesenchymal stromal cells give superior results in knee osteoarthritis? Meta-analysis of randomized controlled trials. J Clin Orthop Trauma 2022; 25:101772. [PMID: 35127439 PMCID: PMC8803619 DOI: 10.1016/j.jcot.2022.101772] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/06/2022] [Accepted: 01/13/2022] [Indexed: 02/08/2023] Open
Abstract
STUDY DESIGN Meta-analysis. OBJECTIVES We aim to analyze and compare the efficacy and safety of vehicle-based delivery of Mesenchymal Stromal Cells (MSCs) in the management of osteoarthritis of the knee from Randomized Controlled Trials (RCTs) available in the literature. MATERIALS AND METHODS We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till August 2021 for RCTs analyzing the efficacy and safety of vehicle-based delivery of MSCs in the management of knee osteoarthritis. Visual Analog Score (VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software. RESULTS 21 studies involving 936 patients were included for analysis. None of the studies made a direct comparison of the direct and vehicle-based delivery of MSCs, hence we pooled the results of all the included studies of both groups and made a comparative analysis of their outcomes. Although at 6 months, both direct and vehicle-based delivery of MSCs showed significantly better VAS improvement (p = 0.002, p = 0.010), it was not consistent at 1 year for the vehicle delivery (p = 0.973). During 6 months and 12 months, direct delivery of MSCs (p < 0.001, p < 0.001) outperformed vehicle delivery (p = 0.969, p = 0.922) compared to their control based on WOMAC scores respectively. Both direct (p = 0.713) and vehicle-based delivery (p = 0.123) of MSCs did not produce significant adverse events compared to their controls. CONCLUSION Our analysis of literature showed that current clinically employed methods of vehicle-based delivery of MSCs such as platelet-rich plasma, hyaluronic acid did not demonstrate superior results compared to direct delivery, concerning the efficacy of treatment measured by improvement in pain, functional outcomes, and safety. Hence, we urge future clinical trials to be conducted to validate the effectiveness of advanced delivery vehicles such as composite bioscaffolds to establish their practical utility in cartilage regeneration with respect to its encouraging in-vitro evidence.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
| | - B Shivaraj
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
- Dr. RML National Law University, Lucknow, Uttar Pradesh, India
| | - Shiva Kumar Bingi
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
- Dr. RML National Law University, Lucknow, Uttar Pradesh, India
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu, India
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India
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Zeng W, Wang G, Liao X, Pei C. Efficacy of Intra-Articular Injection of Platelet-Rich Plasma Combined with Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Int J Clin Pract 2022; 2022:2192474. [PMID: 36263242 PMCID: PMC9553671 DOI: 10.1155/2022/2192474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/30/2022] [Accepted: 09/03/2022] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE This study systematically evaluated the effect of intra-articular injection of platelet-rich plasma (PRP) and mesenchymal stem cells (MSC) on knee osteoarthritis (KOA). METHODS Randomized controlled trials (RCTs) of PRP combined with MSC in the treatment of KOA were collected from PubMed, Cochrane Library, Web of Science, Wiley online library, CNKI, and Wanfang databases from inception to July 30, 2022. Two researchers read and screened the literature to extract the data, respectively. After conducting a risk-of-bias assessment of included data, RevMan 5.3 software was used for meta-analysis. The Cochrane Handbook risk-of-bias assessment tool was used to evaluate the included literature. RESULTS A total of 9 papers with 480 KOA patients were included in this study. Significant differences in terms of visual analogue scale (VAS) score (MD = -1.10, 95% CI -1.91 to -0.29), P = 0.008) and knee injury and osteoarthritis outcome score (KOOS) (MD = 4.56, 95% CI 0.54-8.58, P = 0.050) were noted between the 2 groups. Subgroup analysis found that MD = 1.66 in KOOS-pain-1 group (95% CI (0.10, 3.22), P = 0.040), which is significant. The MD for KOOS total score and IKDC scores between the two groups was MD = 6.31 (95% CI 2.73-9.88, P = 0.0005) and MD = 3.05 (95% CI -7.09-13.20, P = 0.56), respectively. CONCLUSION The results of this study provide a theoretical basis for the clinical treatment of KOA with PRP combined with MSC.
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Affiliation(s)
- Weipeng Zeng
- Department of Joint Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, China
| | - Gongze Wang
- Department of Sports Medicine, Qionghai People's Hospital, Qionghai 571400, China
| | - Xinping Liao
- Department of Joint Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, China
| | - Caifeng Pei
- Department of Orthopedics, People's Hospital of Wanning Hainan, Hainan 571500, China
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Muthu S, Kartheek RR, Jeyaraman N, Rajendran RL, Khanna M, Jeyaraman M, Packkyarathinam RP, Gangadaran P, Ahn BC. Is Culture Expansion Necessary in Autologous Mesenchymal Stromal Cell Therapy to Obtain Superior Results in the Management of Knee Osteoarthritis?-Meta-Analysis of Randomized Controlled Trials. Bioengineering (Basel) 2021; 8:bioengineering8120220. [PMID: 34940373 PMCID: PMC8698637 DOI: 10.3390/bioengineering8120220] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/10/2021] [Accepted: 12/15/2021] [Indexed: 02/05/2023] Open
Abstract
Study Design: Meta-analysis. Objectives: We aimed to analyze the impact of cultured expansion of autologous mesenchymal stromal cells (MSCs) in the management of osteoarthritis of the knee from randomized controlled trials (RCTs) available in the literature. Materials and Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library until August 2021 for RCTs analyzing the efficacy and safety of culture-expanded compared to non-cultured autologous MSCs in the management of knee osteoarthritis. The Visual Analog Score (VAS) for pain, Western Ontario McMaster University's Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the analyzed outcomes. Analysis was performed in R-platform using OpenMeta [Analyst] software. Results: Overall, 17 studies involving 767 patients were included for analysis. None of the studies made a direct comparison of the culture expanded and non-cultured MSCs, hence we pooled the results of all the included studies of non-cultured and cultured types of MSC sources and made a comparative analysis of the outcomes. At six months, culture expanded MSCs showed significantly better improvement (p < 0.001) in VAS outcome. Uncultured MSCs, on the other hand, demonstrated significant VAS improvement in the long term (12 months) in VAS (p < 0.001), WOMAC (p = 0.025), KOOS score (p = 0.016) where cultured-expanded MSCs failed to demonstrate a significant change. Culturing of MSCs did not significantly increase the complications noted (p = 0.485). On sub-group analysis, adipose-derived uncultured MSCs outperformed culture-expanded MSCs at both short term (six months) and long term (12 months) in functional outcome parameters such as WOMAC (p < 0.001, p = 0.025), Lysholm (p < 0.006), and KOOS (p < 0.003) scores, respectively, compared to their controls. Conclusions: We identified a void in literature evaluating the impact of culture expansion of MSCs for use in knee osteoarthritis. Our indirect analysis of literature showed that culture expansion of autologous MSCs is not a necessary factor to obtain superior results in the management of knee osteoarthritis. Moreover, while using uncultured autologous MSCs, we recommend MSCs of adipose origin to obtain superior functional outcomes. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the need for culture expansion of MSCs for use in cellular therapy of knee osteoarthritis.
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Affiliation(s)
- Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India;
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India; (R.R.K.); (N.J.); (M.K.)
| | - Randhi Rama Kartheek
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India; (R.R.K.); (N.J.); (M.K.)
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226010, Uttar Pradesh, India
| | - Naveen Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India; (R.R.K.); (N.J.); (M.K.)
- Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow 226010, Uttar Pradesh, India
- Department of Orthopaedics, Atlas Hospitals, Tiruchirappalli 620002, Tamil Nadu, India
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India; (R.R.K.); (N.J.); (M.K.)
- Department of Orthopaedics, Prasad Institute of Medical Sciences, Lucknow 226401, Uttar Pradesh, India
| | - Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India; (R.R.K.); (N.J.); (M.K.)
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Correspondence: (M.J.); (R.P.P.); (P.G.); (B.-C.A.)
| | - Rathinavelpandian Perunchezhian Packkyarathinam
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 226010, Uttar Pradesh, India; (R.R.K.); (N.J.); (M.K.)
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
- Correspondence: (M.J.); (R.P.P.); (P.G.); (B.-C.A.)
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
- Correspondence: (M.J.); (R.P.P.); (P.G.); (B.-C.A.)
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
- Correspondence: (M.J.); (R.P.P.); (P.G.); (B.-C.A.)
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