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1
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Roseti L, Cavallo C, Desando G, D’Alessandro M, Grigolo B. Forty Years of the Use of Cells for Cartilage Regeneration: The Research Side. Pharmaceutics 2024; 16:1622. [PMID: 39771600 PMCID: PMC11677864 DOI: 10.3390/pharmaceutics16121622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/13/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025] Open
Abstract
Background: The treatment of articular cartilage damage has always represented a problem of considerable practical interest for orthopedics. Over the years, many surgical techniques have been proposed to induce the growth of repairing tissue and limit degeneration. In 1994, the turning point occurred: implanted autologous cells paved the way for a new treatment option based more on regeneration than repair. Objectives: This review aims to outline biological and clinical advances, from the use of mature adult chondrocytes to cell-derived products, going through progenitor cells derived from bone marrow or adipose tissue and their concentrates for articular cartilage repair. Moreover, it highlights the relevance of gene therapy as a valuable tool for successfully implementing current regenerative treatments, and overcoming the limitations of the local delivery of growth factors. Conclusions: Finally, this review concludes with an outlook on the importance of understanding the role and mechanisms of action of the different cell compounds with a view to implementing personalized treatments.
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Affiliation(s)
| | - Carola Cavallo
- Laboratorio RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano, 1/10, 40136 Bologna, Italy; (L.R.); (G.D.); (M.D.); (B.G.)
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Yazdi AA, Weissman AC, Wagner KR, Muth SA, Rubin JM, Gilat R, Cole BJ. Men and women demonstrate comparable rates of failures and reoperations following primary osteochondral allograft transplantation of the knee, but women undergo reoperation sooner. Knee Surg Sports Traumatol Arthrosc 2024; 32:2622-2634. [PMID: 39396150 DOI: 10.1002/ksa.12507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 09/07/2024] [Accepted: 09/10/2024] [Indexed: 10/14/2024]
Abstract
PURPOSE To compare the differences between men and women who receive primary osteochondral allograft transplantation of the knee with regard to preoperative disease presentation, failures and reoperations. METHODS A retrospective review of patients ≥18 years old who underwent primary osteochondral allograft transplantation between 2002 and 2020 by a single surgeon with a minimum of 2-year follow-up was performed. Demographic, preoperative, intraoperative and postoperative data were collected for all included patients. Patients were then assigned to two groups, either male or female, based on their reported sex. Statistical analysis was performed to assess sex-related differences in baseline characteristics, comparative survival analysis for determining survival probabilities, and regression analysis for determining variables associated with subsequent reoperation or failure. RESULTS Among the 437 patients that were identified, 337 patients (77.1% follow-up, 161 men, 176 women) with a minimum of 2-year follow-up were included in our study. The mean age of included patients was 31.3 ± 9.9 years (range, 18.0-55.9), with a BMI of 26.7 ± 4.4 (range, 19.0-39.0) and a mean follow-up of 5.6 ± 2.6 years (range, 2.0-16.3). Male patients had significantly higher body mass index (BMI) (p ≤ 0.01), were more likely to have lesions on the medial femoral condyle (p = 0.041), and had larger lesions at the medial femoral condyle (p ≤ 0.01) and lateral femoral condyle (p ≤ 0.01). 36.8% of patients experienced subsequent reoperation (59 male, 65 female). Mean time to reoperation was 3.5 ± 2.8 years (range, 0.4-16.3 years) in males and 2.1 ± 1.9 years (range, 0.1-13.5 years) in females. No significant difference was found between the two groups with regard to reoperation rates (n.s.) or survivability free from reoperation (n.s.), but females were found to undergo reoperation sooner (p = 0.028). Sixty-three (18.7%) patients experienced subsequent graft failure (36 male, 27 female). No significant difference was found between the two groups in terms of failure rates, time to failure, survivability free from failure, or mode of failure (n.s. for all). CONCLUSIONS Despite several differences in baseline demographics and intraoperative variables, no significant differences were found between men and women receiving primary osteochondral allograft transplantation of the knee with regard to failure or reoperation, with the exception that women underwent reoperation sooner. STUDY DESIGN Retrospective Comparative Cohort Study. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Allen A Yazdi
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA
| | | | - Kyle R Wagner
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA
| | - Sarah A Muth
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA
| | - Jared M Rubin
- University of Illinois College of Medicine, Chicago, Illinois, USA
| | - Ron Gilat
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA
| | - Brian J Cole
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA
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Chatterjee P, Stevens HY, Kippner LE, Bowles-Welch AC, Drissi H, Mautner K, Yeago C, Gibson G, Roy K. Single-cell transcriptome and crosstalk analysis reveals immune alterations and key pathways in the bone marrow of knee OA patients. iScience 2024; 27:110827. [PMID: 39310769 PMCID: PMC11416684 DOI: 10.1016/j.isci.2024.110827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 06/10/2024] [Accepted: 08/22/2024] [Indexed: 09/25/2024] Open
Abstract
Knee osteoarthritis (OA) is a significant medical and economic burden. To understand systemic immune effects, we performed deep exploration of bone marrow aspirate concentrates (BMACs) from knee-OA patients via single-cell RNA sequencing and proteomic analyses from a randomized clinical trial (MILES: NCT03818737). We found significant cellular and immune alterations in the bone marrow, specifically in MSCs, T cells and NK cells, along with changes in intra-tissue cellular crosstalk during OA progression. Unlike previous studies focusing on injury sites or peripheral blood, our probe into the bone marrow-an inflammation and immune regulation hub-highlights remote organ impact of OA, identifying cell types and pathways for potential therapeutic targeting. Our findings highlight increased cellular senescence and inflammatory pathways, revealing key upstream genes, transcription factors, and ligands. Additionally, we identified significant enrichment in key biological pathways like PI3-AKT-mTOR signaling and IFN responses, showing their potentially crucial role in OA onset and progression.
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Affiliation(s)
- Paramita Chatterjee
- Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA
| | - Hazel Y. Stevens
- Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA
| | - Linda E. Kippner
- Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA
| | - Annie C. Bowles-Welch
- Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA
| | - Hicham Drissi
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Kenneth Mautner
- Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Carolyn Yeago
- The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA
| | - Greg Gibson
- School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Krishnendu Roy
- Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- Department of Biomedical Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA
- Department of Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, TN, USA
- Department of Chemical and Biomolecular Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA
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Chandrashekar S, Jeyaraman M, Mounissamy P, Jeyaraman N, Khanna M, Gupta A. Safety and Efficacy of Bone-Marrow Aspirate Concentrate in Hip Osteoarthritis: A Systematic Review of Current Clinical Evidence. Indian J Orthop 2024; 58:835-844. [PMID: 38948376 PMCID: PMC11208346 DOI: 10.1007/s43465-024-01183-7] [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: 03/30/2024] [Accepted: 05/04/2024] [Indexed: 07/02/2024]
Abstract
Introduction Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA. Materials and methods The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were "osteoarthritis" OR "hip osteoarthritis" OR "orthobiologics" OR "efficacy or use of orthobiologic treatment" OR "bone-marrow concentrate" OR "bone-marrow aspirate concentrate", AND "BMAC". The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA. Results A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL). Conclusion The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.
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Affiliation(s)
- Sushma Chandrashekar
- Fellow in Orthopaedic Rheumatology, Dr RML National Law University, Lucknow, 226010 Uttar Pradesh India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, 600077 Tamil Nadu India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
- Department of Orthopaedics, South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045 USA
| | - Prabu Mounissamy
- Department of Orthopaedics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006 India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, 600077 Tamil Nadu India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
- Department of Orthopaedics, Dr KNS Mayo Institute of Medical Sciences, Lucknow, 225001 Uttar Pradesh India
| | - Ashim Gupta
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, 226010 Uttar Pradesh India
- Department of Orthopaedics, South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045 USA
- Regenerative Orthopaedics, Noida, 201301 Uttar Pradesh India
- Future Biologics, Lawrenceville, GA 30043 USA
- BioIntegrate, Lawrenceville, GA 30043 USA
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Centeno CJ, Fausel Z, Dodson E, Berger DR, Steinmetz NJ. Percutaneous bone marrow concentrate and platelet products versus exercise therapy for the treatment of rotator cuff tears: a randomized controlled, crossover trial with 2-year follow-up. BMC Musculoskelet Disord 2024; 25:392. [PMID: 38762734 PMCID: PMC11102209 DOI: 10.1186/s12891-024-07519-6] [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: 12/18/2023] [Accepted: 05/13/2024] [Indexed: 05/20/2024] Open
Abstract
BACKGROUND Surgical repair is recommended for the treatment of high-grade partial and full thickness rotator cuff tears, although evidence shows surgery is not necessarily superior to non-surgical therapy. The purpose of this study was to compare percutaneous orthobiologic treatment to a home exercise therapy program for supraspinatus tears. METHODS In this randomized-controlled, crossover design, participants with a torn supraspinatus tendon received either 'BMC treatment', consisting of a combination of autologous bone marrow concentrate (BMC) and platelet products, or underwent a home exercise therapy program. After three months, patients randomized to exercise therapy could crossover to receive BMC treatment if not satisfied with shoulder progression. Patient-reported outcomes of Numeric Pain Scale (NPS), Disabilities of the Arm, Shoulder, and Hand, (DASH), and a modified Single Assessment Numeric Evaluation (SANE) were collected at 1, 3, 6, 12, and 24 months. Pre- and post-treatment MRI were assessed using the Snyder Classification system. RESULTS Fifty-one patients were enrolled and randomized to the BMC treatment group (n = 34) or the exercise therapy group (n = 17). Significantly greater improvement in median ΔDASH, ΔNPS, and SANE scores were reported by the BMC treatment group compared to the exercise therapy group (-11.7 vs -3.8, P = 0.01; -2.0 vs 0.5, P = 0.004; and 50.0 vs 0.0, P < 0.001; respectively) after three months. Patient-reported outcomes continued to progress through the study's two-year follow-up period without a serious adverse event. Of patients with both pre- and post-treatment MRIs, a majority (73%) showed evidence of healing post-BMC treatment. CONCLUSIONS Patients reported significantly greater changes in function, pain, and overall improvement following BMC treatment compared to exercise therapy for high grade partial and full thickness supraspinatus tears. TRIAL REGISTRATION This protocol was registered with www. CLINICALTRIALS gov (NCT01788683; 11/02/2013).
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Affiliation(s)
- Christopher J Centeno
- Centeno-Schultz Clinic, Broomfield, CO, 80021, USA
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA
| | - Zachary Fausel
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA
| | - Ehren Dodson
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA.
| | - Dustin R Berger
- Regenexx, LLC, Research and Development, Broomfield, CO, 80021, USA
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Vlashi R, Zhang X, Li H, Chen G. Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing. Rev Endocr Metab Disord 2024; 25:339-367. [PMID: 38055160 DOI: 10.1007/s11154-023-09860-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2023] [Indexed: 12/07/2023]
Abstract
Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.
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Affiliation(s)
- Rexhina Vlashi
- College of Life Science and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Xingen Zhang
- Department of Orthopedics, Jiaxing Key Laboratory for Minimally Invasive Surgery in Orthopaedics & Skeletal Regenerative Medicine, Zhejiang Rongjun Hospital, Jiaxing, 314001, China
| | - Haibo Li
- The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children's Hospital, Ningbo, China.
- Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases, Ningbo Women and Children's Hospital, Ningbo, China.
| | - Guiqian Chen
- College of Life Science and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
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Balusani P, Shrivastava S, Pundkar A, Kale P. Navigating the Therapeutic Landscape: A Comprehensive Review of Platelet-Rich Plasma and Bone Marrow Aspirate Concentrate in Knee Osteoarthritis. Cureus 2024; 16:e54747. [PMID: 38524005 PMCID: PMC10960965 DOI: 10.7759/cureus.54747] [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: 12/07/2023] [Accepted: 02/23/2024] [Indexed: 03/26/2024] Open
Abstract
This comprehensive review provides an in-depth analysis of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) as potential treatments for knee osteoarthritis. It explores their mechanisms of action, clinical efficacy, safety considerations, and the importance of personalised treatment approaches. The review highlights promising findings regarding the ability of PRP and BMAC to alleviate symptoms, improve joint function, and potentially slow disease progression. It emphasises the need for further research into long-term outcomes, direct comparative studies, protocol standardisation, biomarker identification, and cost-effectiveness assessments to enhance clinical practice. While the review does not directly compare PRP and BMAC, it provides valuable insights into their respective roles in knee osteoarthritis management. The review aims to contribute to evidence-based advancements in regenerative therapies for knee osteoarthritis by addressing critical research priorities and refining treatment strategies.
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Affiliation(s)
- Prashanth Balusani
- Orthopaedics and Traumatology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Science, Wardha, IND
| | - Sandeep Shrivastava
- Orthopaedic Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Science, Wardha, IND
| | - Aditya Pundkar
- Orthopaedics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Science, Wardha, IND
| | - Prathamesh Kale
- Orthopaedic Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Science, Wardha, IND
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Kolar M, Veber M, Girandon L, Drobnič M. Biomaterials augmented with filtered bone marrow aspirate for the treatment of talar osteochondral lesions. A comparison of clinical and cellular parameters. J Orthop Surg (Hong Kong) 2024; 32:10225536231219970. [PMID: 38214308 DOI: 10.1177/10225536231219970] [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] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Biomaterials augmented with Bone Marrow Aspirate Concentrate (BMAC) are becoming increasingly utilized in the cartilage treatment. However, the potential role of cellular parameters in the intraoperatively applied BMAC have yet to be elucidated. PURPOSE (A) To evaluate clinical outcomes and safety of a combined single-step approach with scaffolds (fibrin glues, collagen gels, collagen-hydroxyapatite membrane) and filtered Bone Marrow Aspirate (fBMA) for the treatment of osteochondral lesions of the talus (OLTs). (B) To identify significant factors for postoperative improvements, considering cellular parameters as potential predictors. METHODS All the patients operated on due to OLTs by the combination above were selected from the hospital registry database (35 pts, years 16-55, and minimally 1 year follow-up). Treatment outcomes were followed clinically with Patient-reported outcome measures (PROMs), and by pursuing serious adverse events (SAE) and graft failures (GF). Cellular parameters of the injected fBMA were determined. Pre- and postoperative PROMs values were compared to evaluate postoperative improvements. Multivariable regression models were applied to identify potential factors (demographics, medical history, joint and lesion characteristics, scaffold type, surgical and cellular parameters) that predict the treatment outcomes. RESULTS At the mean follow-up of 32.2 (12.5) months, all Foot and Ankle Outcome Score (FAOS) and European Quality of Life in Five Dimensions Three-Level (EQ-5D-3 L) values improved significantly. 4 (11%) SAE (3 arthrofibrosis, one hardware removal), and 3 (9%) GF occurred. Female gender and concomitant procedures were the main negative predictors for postoperative outcomes. The number of fibroblast colony forming units (CFU-F) or their proportion among total nucleated cells (CFU-F/TNC) were positively correlated with the improvements of some PROMs. CONCLUSIONS Scaffolds augmented with fBMA proved as an adequate and safe approach for OLTs treatment. Cellular parameters seem to influence the treatment outcomes, thus further attention should be given to the intraoperatively applied products. LEVEL OF EVIDENCE Level IV.
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Affiliation(s)
- Matic Kolar
- Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Chair of Orthopaedics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | | | | | - Matej Drobnič
- Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Chair of Orthopaedics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Zhang K, Yu J, Li J, Fu W. The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis. Am J Sports Med 2024; 52:140-154. [PMID: 38164685 DOI: 10.1177/03635465231212668] [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] [Indexed: 01/03/2024]
Abstract
BACKGROUND Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. PURPOSE/HYPOTHESIS The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. STUDY DESIGN Controlled laboratory study. METHODS A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. RESULTS Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. CONCLUSION IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. CLINICAL RELEVANCE Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.
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Affiliation(s)
- Kaibo Zhang
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiang Yu
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jian Li
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Weili Fu
- Sports Medicine Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Koyanagi M, Fujioka-Kobayashi M, Inada R, Yoneyama Y, Satomi T. Skin and Bone Regeneration of Solid Bone Marrow Aspirate Concentrate Versus Platelet-Rich Fibrin. Tissue Eng Part A 2023; 29:141-149. [PMID: 36416223 DOI: 10.1089/ten.tea.2022.0175] [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: 11/24/2022] Open
Abstract
Solid bone marrow aspirate concentrate (sBMAC) is harvested from bone marrow aspirate without anticoagulants by a centrifugation protocol similar to that for platelet-rich fibrin (PRF) prepared from peripheral blood. It was hypothesized that sBMAC could accelerate not only wound healing but also bone regeneration because of the abundant growth factor (GF) releases from enriched bone marrow cells. The purpose of the present study was to investigate skin wound healing and bone regenerative potential of sBMAC compared with arterial blood-derived PRF (Ar-PRF) and venous blood-derived PRF (Ve-PRF) in a skin defect and calvarial bone defect model in rabbits. GF release assays revealed significantly higher release of transforming growth factor-β (TGF-β), alkaline phosphatase (ALP), and osteocalcin (OCN) from sBMAC compared with PRFs for 24 h. In the skin defect animal model, sBMAC and PRFs promoted wound bed angiogenesis and re-epithelization in skin defect sites with higher collagen 1 synthesis, cytokeratin AE1/AE3, vascular endothelial growth factor (VEGF) expressions on week 1. Furthermore, a calvarial defect assay revealed that sBMAC promoted new bone formation with a sufficient bone marrow structure similar to that of intact bone in the bone defects. Ar-PRF achieved the second highest bone closure and new bone volume but yielded new bone that was thinner than the intact bone. In conclusion, sBMAC treatment might be a good option instead of PRF as an adjuvant therapy for both skin and bone tissue regeneration therapies in certain clinical situations. Impact statement Solid bone marrow aspirate concentrate (sBMAC) is new type of clot material prepared from bone marrow aspirate. The present study for the first time showed that sBMAC significantly accelerated both skin wound healing and bone formation in the defects, compared with conventional platelet-rich fibrin in rabbit experiment models.
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Affiliation(s)
- Masateru Koyanagi
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, Chiyoda-ku, Japan
| | - Masako Fujioka-Kobayashi
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, Chiyoda-ku, Japan
| | - Ryo Inada
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, Chiyoda-ku, Japan
| | - Yuya Yoneyama
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, Chiyoda-ku, Japan
| | - Takafumi Satomi
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, Chiyoda-ku, Japan
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11
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Oloff LM, Wilhelm I, Vora NS. Orthobiologic Use in Sports Injuries. Clin Podiatr Med Surg 2023; 40:169-179. [PMID: 36368841 DOI: 10.1016/j.cpm.2022.07.011] [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: 11/25/2022]
Abstract
Orthobiologics have gained much popularity in recent years but there has not been a large amount of clinical evidence to support their use. In the limited research that has been published, they have been shown to be effective and safe. They can assist in earlier return to activity with the avoidance of surgery. They can also augment current surgical practice to aid in healing and return to sport with few complications. With new medical innovation, there is unfortunately a higher cost for these products. The use of orthobiologics will only grow and so will the need for high-level clinical evidence.
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Affiliation(s)
- Lawrence M Oloff
- Saint Mary's Medical Center, 450 Stanyan Street, San Francisco, CA 94117, USA.
| | - Isaac Wilhelm
- Saint Mary's Medical Center, 450 Stanyan Street, San Francisco, CA 94117, USA
| | - Nishit S Vora
- 1501 Trousdale Drive, Suite 115, Burlingame, CA 94010, USA
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12
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Lana JFSD, Sugano AA, De Barros HV, Mosaner T, Santos GS, Lana JVB, Vicente R, De Andrade MAP. Full Recovery from O'Donoghue's Triad with Autologous Bone Marrow Aspirate Matrix: A Case Report. J Funct Morphol Kinesiol 2022; 7:jfmk7040100. [PMID: 36412762 PMCID: PMC9680402 DOI: 10.3390/jfmk7040100] [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: 09/19/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 11/16/2022] Open
Abstract
O'Donoghue's triad is an extremely debilitating condition. Although there are many conventional treatments available, there is still no consensus regarding the most effective rehabilitation protocol for a full recovery. Surgical interventions have become an ordinary consideration, but problems may still persist even after the surgical procedure. Orthobiologics, however, have gained considerable popularity in regenerative medicine. Notable autologous alternatives, such as bone marrow aspirate (BMA), are often utilized in clinical settings. To our knowledge, the administration of BMA products for the management of O'Donoghue's triad has not been thoroughly investigated in the literature. In this case report we describe a full recovery from O'Donoghue's triad with BMA matrix in a patient who was recalcitrant to surgical intervention due to fear of complications. Our patient received three BMA matrix injections with four-week intervals, exhibiting significant recovery according to pain scores, functional assessment outcomes, and magnetic resonance imaging (MRI) results. The patient returned to normal activities with no complaints and MRI evidence at follow-up showed significant signs of structural restoration of the musculoskeletal tissues. Here, we demonstrate that autologous BMA products are a feasible alternative for the accelerated recovery of musculoskeletal tissue injury with safety and efficacy.
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Affiliation(s)
| | - André Atsushi Sugano
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | | | - Tomas Mosaner
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Gabriel Silva Santos
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
- Correspondence:
| | - João Vitor Bizinotto Lana
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Rodrigo Vicente
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
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13
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Augmented Marrow Stimulation: Drilling Techniques and Scaffold Options. OPER TECHN SPORT MED 2022. [DOI: 10.1016/j.otsm.2022.150958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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14
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Hede K, Christensen BB, Jensen J, Foldager CB, Lind M. Combined Bone Marrow Aspirate and Platelet-Rich Plasma for Cartilage Repair: Two-Year Clinical Results. Cartilage 2021; 13:937S-947S. [PMID: 31538811 PMCID: PMC8808891 DOI: 10.1177/1947603519876329] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
PURPOSE To evaluate the clinical and biological outcome of combined bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) on a collagen scaffold for treating cartilage lesions in the knee. METHODS AND MATERIALS Ten patients (mean age 29.4 years, range 18-36) suffering from large full-thickness cartilage in the knee were treated with BMAC and PRP from January 2015 to December 2016. In a 1-step procedure autologous BMAC and PRP was seeded onto a collagen scaffold and sutured into the debrided defect. Patients were evaluated by clinical outcome scores (IKDC [International Knee Documentation Committee Subjective Knee Form], KOOS [Knee Injury and Osteoarthritis Outcome Score], and pain score using the Numeric Rating Scale [NRS]) preoperatively, after 3 months, and after 1 and 2 years. Second-look arthroscopies were performed (n = 7) with biopsies of the repair tissue for histology. All patients had magnetic resonance imaging (MRI) preoperatively, after 1 year, and after 2 to 3.5 years with MOCART (magnetic resonance observation of cartilage repair tissue) scores evaluating cartilage repair. RESULTS After 1 year significant improvements were found in IKDC, KOOS symptoms, KOOS ADL (Activities of Daily Living), KOOS QOL (Quality of Life), and pain at activity. At the latest follow-up significant improvements were seen in IKDC, KOOS symptoms, KOOS QOL, pain at rest, and pain at activity. MRI MOCART score for cartilage repair improved significantly from baseline to 1-year follow-up. Histomorphometry of repair tissue demonstrated a mixture of fibrous tissue (58%) and fibrocartilage (40%). CONCLUSION Treatment of cartilage injuries using combined BMAC and PRP improved subjective clinical outcome scores and pain scores at 1 and 2 years postoperatively. MRI and histology indicated repair tissue inferior to the native hyaline cartilage.
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Affiliation(s)
- Kris Hede
- Orthopedic Research Laboratory, Aarhus
University Hospital, Aarhus N, Denmark,Kris Tvilum Chadwick Hede, Orthopaedic
Research Lab, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99,
Section J, Level 1, Aarhus 8200, Denmark.
| | | | - Jonas Jensen
- Department of Radiology, Aarhus
University Hospital, Aarhus N, Denmark
| | - Casper B. Foldager
- Orthopedic Research Laboratory, Aarhus
University Hospital, Aarhus N, Denmark,Department of Orthopedics, Aarhus
University Hospital, Aarhus N, Denmark
| | - Martin Lind
- Department of Orthopedics, Aarhus
University Hospital, Aarhus N, Denmark
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15
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El-Kadiry AEH, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne) 2021; 8:756029. [PMID: 34881261 PMCID: PMC8645794 DOI: 10.3389/fmed.2021.756029] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non-stem cell-based cell therapies, and create the first-in-literature compilation of the different "multicellular" therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas-regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.
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Affiliation(s)
- Abed El-Hakim El-Kadiry
- Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, Research Center, Montreal, QC, Canada
- Department of Biomedical Sciences, Université de Montréal, Montreal, QC, Canada
| | - Moutih Rafei
- Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada
- Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada
- Molecular Biology Program, Université de Montréal, Montreal, QC, Canada
- Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
| | - Riam Shammaa
- Canadian Centre for Regenerative Therapy, Toronto, ON, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
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16
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Hulme CH, Perry J, McCarthy HS, Wright KT, Snow M, Mennan C, Roberts S. Cell therapy for cartilage repair. Emerg Top Life Sci 2021; 5:575-589. [PMID: 34423830 PMCID: PMC8589441 DOI: 10.1042/etls20210015] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/27/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023]
Abstract
Regenerative medicine, using cells as therapeutic agents for the repair or regeneration of tissues and organs, offers great hope for the future of medicine. Cell therapy for treating defects in articular cartilage has been an exemplar of translating this technology to the clinic, but it is not without its challenges. These include applying regulations, which were designed for pharmaceutical agents, to living cells. In addition, using autologous cells as the therapeutic agent brings additional costs and logistical challenges compared with using allogeneic cells. The main cell types used in treating chondral or osteochondral defects in joints to date are chondrocytes and mesenchymal stromal cells derived from various sources such as bone marrow, adipose tissue or umbilical cord. This review discusses some of their biology and pre-clinical studies before describing the most pertinent clinical trials in this area.
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Affiliation(s)
- Charlotte H. Hulme
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Jade Perry
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Helen S. McCarthy
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Karina T. Wright
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Martyn Snow
- The Royal Orthopaedic Hospital, Birmingham, U.K
| | - Claire Mennan
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
| | - Sally Roberts
- School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire, U.K
- Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, U.K
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17
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Tamaddon M, Blunn G, Xu W, Alemán Domínguez ME, Monzón M, Donaldson J, Skinner J, Arnett TR, Wang L, Liu C. Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects. Bone Joint Res 2021; 10:677-689. [PMID: 34665001 PMCID: PMC8559972 DOI: 10.1302/2046-3758.1010.bjr-2020-0504.r1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Aims Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. Methods The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. Results The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. Conclusion Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677–689.
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Affiliation(s)
- Maryam Tamaddon
- Institute of Orthopaedic & Musculoskeletal Science, Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, London, UK
| | - Gordon Blunn
- School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
| | - Wei Xu
- Beijing Advanced Innovation Center for Materials Genome Engineering, Institute for Advanced Materials and Technology, State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing, China
| | | | - Mario Monzón
- Departamento de Ingeniería Mecánica, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain
| | - James Donaldson
- Knee and Hip Unit, Royal National Orthopaedic Hospital, London, UK
| | - John Skinner
- Institute of Orthopaedic & Musculoskeletal Science, Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, London, UK.,Knee and Hip Unit, Royal National Orthopaedic Hospital, London, UK
| | - Timothy R Arnett
- Department of Cell and Developmental Biology, University College London, London, UK
| | - Ling Wang
- State Key Laboratory for Manufacturing System Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, China
| | - Chaozong Liu
- Institute of Orthopaedic & Musculoskeletal Science, Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, London, UK
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18
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Massey PA, McClary KN, McBride HD, Walt J, Mielke CH, Barton RS. Arthroscopic Fixation of Knee Femoral Condyle Osteochondritis Dissecans Fragment With Bone Marrow Aspirate Concentrate. Arthrosc Tech 2021; 10:e2357-e2363. [PMID: 34754745 PMCID: PMC8556664 DOI: 10.1016/j.eats.2021.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 07/02/2021] [Indexed: 02/03/2023] Open
Abstract
This article reviews a technique for arthroscopic fixation of an osteochondritis dissecans fragment with bone marrow aspirate concentrate augmentation. This technique involves safe harvest of bone marrow arthroscopically from the intercondylar notch, proper preparation and debridement of the parent bone, reduction of the progeny osteochondritis dissecans fragment, insertion of the bone marrow aspirate concentrate, and placement of multiple headless compression screws for fixation.
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Affiliation(s)
- Patrick A. Massey
- Department of Orthopaedic Surgery, Louisiana State University, Shreveport, Louisiana, U.S.A.,Address correspondence to Patrick A. Massey, M.D., Department of Orthopaedic Surgery, Louisiana State University, 1501 Kings Hwy, Shreveport, LA 71103, U.S.A.
| | - Kaylan N. McClary
- Department of Orthopaedic Surgery, Louisiana State University, Shreveport, Louisiana, U.S.A
| | - Hayden D. McBride
- School of Medicine, Louisiana State University, Shreveport, Louisiana, U.S.A
| | - Jennifer Walt
- Department of Orthopaedic Surgery, Louisiana State University, Shreveport, Louisiana, U.S.A
| | - Cary H. Mielke
- Department of Orthopaedic Surgery, Shriners Hospitals for Children, Shreveport, Louisiana, U.S.A
| | - R. Shane Barton
- Department of Orthopaedic Surgery, Louisiana State University, Shreveport, Louisiana, U.S.A
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19
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Glenn R, Johns W, Walley K, Jackson JB, Gonzalez T. Topical Review: Bone Marrow Aspirate Concentrate and Its Clinical Use in Foot and Ankle Surgery. Foot Ankle Int 2021; 42:1205-1211. [PMID: 34219485 DOI: 10.1177/10711007211021017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Bone marrow aspirate concentrate (BMAC) is now commonly used in orthopedic surgery. Animal studies showed promising results for cartilage, bone, and soft tissue healing; however, many of these outcomes have yet to be translated to human models. While there has been an increase in the use of BMAC in foot and ankle procedures, the associated clinical evidence is limited. The purpose of this review is to analyze the existing literature in order to evaluate the safety and efficacy of BMAC in foot and ankle surgery.
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Affiliation(s)
- Rachel Glenn
- Department of Orthopaedic Surgery, Prisma Health Richland Hospital/University of South Carolina, Columbia, SC, USA
| | - William Johns
- Department of Orthopaedic Surgery, Rothman Orthopaedic Institute at Jefferson Health, Philadelphia, PA, USA
| | - Kempland Walley
- Department of Orthopaedic Surgery, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - J Benjamin Jackson
- Department of Orthopaedic Surgery, Prisma Health Richland Hospital/University of South Carolina, Columbia, SC, USA
| | - Tyler Gonzalez
- Department of Orthopaedic Surgery, Prisma Health Richland Hospital/University of South Carolina, Columbia, SC, USA
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20
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Lan T, McCarthy HS, Hulme CH, Wright KT, Makwana N. The management of talar osteochondral lesions - Current concepts. JOURNAL OF ARTHROSCOPY AND JOINT SURGERY 2021; 8:231-237. [PMID: 34337329 PMCID: PMC8312263 DOI: 10.1016/j.jajs.2021.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 04/05/2021] [Indexed: 11/17/2022]
Abstract
Osteochondral lesions of the talus (OLTs) are a common complication following trauma, involving both the articular cartilage and the underlying subchondral bone, with variable aetiologies and often presenting with non-specific symptoms. Diagnosis of OLTs requires a combination of clinical assessment and imaging and despite many different treatment options, there is no generalised consensus regarding which option is the most effective. Left untreated, OLTs risk progressing to osteoarthritis. Acute non-displaced OLTs can be treated non-operatively. However, OLTs refractory to non-surgical care for three to six months may be suitable for surgical care. In these cases, conservative treatments are often unsuccessful, particularly for larger and more severe defects and so the majority require surgical intervention. Although bone marrow stimulation techniques remain the "gold standard" for lesions <150 mm2, there still requires a need for better long term clinical data and cost-benefit analyses compared with other treatment options. Biological attempts at either regenerating or replacing the articular cartilage are however demonstrating some promising results, but each with their own advantages and disadvantages. In this review, we summarise the clinical management of OLTs and present the current concepts of different treatment regimes.
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Affiliation(s)
- Tian Lan
- Spinal Studies & Cartilage Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Trust, Oswestry, UK
- School of Pharmacy and Bioengineering, Keele University, UK
| | - Helen S. McCarthy
- Spinal Studies & Cartilage Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Trust, Oswestry, UK
- School of Pharmacy and Bioengineering, Keele University, UK
| | - Charlotte H. Hulme
- Spinal Studies & Cartilage Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Trust, Oswestry, UK
- School of Pharmacy and Bioengineering, Keele University, UK
| | - Karina T. Wright
- Spinal Studies & Cartilage Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Trust, Oswestry, UK
- School of Pharmacy and Bioengineering, Keele University, UK
| | - Nilesh Makwana
- Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Trust, Oswestry, UK
- School of Pharmacy and Bioengineering, Keele University, UK
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21
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Dregalla RC, Herrera JA, Donner EJ. Soluble factors differ in platelets derived from separate niches: a pilot study comparing the secretome of peripheral blood and bone marrow platelets. Cytotherapy 2021; 23:677-682. [PMID: 33678599 DOI: 10.1016/j.jcyt.2021.01.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/30/2020] [Accepted: 01/11/2021] [Indexed: 01/17/2023]
Abstract
BACKGROUND AIMS Platelet-rich plasma (PRP) and bone marrow aspirate are commonly used in orthobiologics for their anti-inflammatory, anabolic/regenerative and immunomodulatory characteristics via platelet degranulation and cell secretions. Although platelets are derived from megakaryocytes in the bone marrow, no attention has been paid to the potential benefits of bone marrow platelets and whether their contents differ from aging platelets in peripheral blood. METHODS In the present study, leukocyte-poor peripheral blood-derived platelets in plasma (LPP) and leukocyte-poor bone marrow platelets in plasma (BMP) were prepared from six donors, activated with calcium chloride, incubated and sampled at day 0, day 3 and day 6. LPP and BMP are platelet preparations intended to evaluate the respective platelet secretomes but are not classified as conventional PRPs, as they are not concentrated to the extent necessary to meet the qualifying criteria. At each time point, 15 growth and immunomodulatory factors were quantitated in LPP and BMP: platelet-derived growth factor AA, basic fibroblast growth factor/fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, hepatocyte growth factor, macrophage colony-stimulating factor, stem cell factor, vascular endothelial growth factor, tumor necrosis factor alpha, IL-1β, interferon gamma, IL-4, IL-10, IL-1 receptor antagonist protein, IL-12p40 and arginase-1. RESULTS The results illustrate that platelets derived from bone marrow have a unique secretome profile compared with those derived from peripheral blood, with significant differences in anti-inflammatory cytokines, which are associated with monocyte polarization. CONCLUSIONS Ultimately, bone marrow-derived platelets may be useful as a stand-alone orthobiologic or as an effective adjuvant to autologous cell therapies where anti-inflammatory and anabolic processes are desired, especially with respect to monocyte function.
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Affiliation(s)
- Ryan C Dregalla
- Elite Regenerative Stem Cell Specialists, LLC, Johnstown, Colorado, USA; R&D Regenerative Laboratory Resources, LLC, Johnstown, Colorado, USA.
| | - Jessica A Herrera
- Elite Regenerative Stem Cell Specialists, LLC, Johnstown, Colorado, USA; R&D Regenerative Laboratory Resources, LLC, Johnstown, Colorado, USA
| | - Edward J Donner
- Elite Regenerative Stem Cell Specialists, LLC, Johnstown, Colorado, USA; R&D Regenerative Laboratory Resources, LLC, Johnstown, Colorado, USA; Colorado Spine Institute, PLLC, Johnstown, Colorado, USA
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22
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Lana JFSD, da Fonseca LF, Macedo RDR, Mosaner T, Murrell W, Kumar A, Purita J, de Andrade MAP. Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects. World J Stem Cells 2021; 13:155-167. [PMID: 33708344 PMCID: PMC7933989 DOI: 10.4252/wjsc.v13.i2.155] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/15/2020] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
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Affiliation(s)
| | | | - Rafael da Rocha Macedo
- Department of Orthopedics, Rede D’Or Unit IFOR Hospital, São Bernardo do Campo 09715-021, SP, Brazil
| | - Tomas Mosaner
- Department of Orthopedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil
| | - William Murrell
- Department of Orthopaedics, Healthpoint UAE, Abu Dhabi 00000, United Arab Emirates
| | - Ashok Kumar
- Department of Orthopaedics, My Doc Specialist Medical Centre, Dubai 00000, United Arab Emirates
| | - Joseph Purita
- Department of Orthopedics, Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
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Mengsteab PY, Otsuka T, McClinton A, Shemshaki NS, Shah S, Kan HM, Obopilwe E, Vella AT, Nair LS, Laurencin CT. Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits. Proc Natl Acad Sci U S A 2020; 117:28655-28666. [PMID: 33144508 PMCID: PMC7682397 DOI: 10.1073/pnas.2012347117] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.
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Affiliation(s)
- Paulos Y Mengsteab
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
| | - Takayoshi Otsuka
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
| | - Aneesah McClinton
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Surgery, University of Connecticut School of Medicine, Farmington, CT, 06030
| | - Nikoo Saveh Shemshaki
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
| | - Shiv Shah
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269
| | - Ho-Man Kan
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
| | - Elifho Obopilwe
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030
| | - Anthony T Vella
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030
| | - Lakshmi S Nair
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269
| | - Cato T Laurencin
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030;
- Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269
- Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030
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A. Everts P, Flanagan II G, Rothenberg J, Mautner K. The Rationale of Autologously Prepared Bone Marrow Aspirate Concentrate for use in Regenerative Medicine Applications. Regen Med 2020. [DOI: 10.5772/intechopen.91310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Kale VP. Transforming growth factor-β boosts the functionality of human bone marrow-derived mesenchymal stromal cells. Cell Biol Int 2020; 44:2293-2306. [PMID: 32749730 DOI: 10.1002/cbin.11437] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 07/17/2020] [Accepted: 08/02/2020] [Indexed: 12/19/2022]
Abstract
Transforming growth factor β1 (TGFβ1) is a negative regulator of hematopoiesis, and yet, it is frequently found at the active sites of hematopoiesis. Here, we show for the first time that bone marrow-derived mononuclear cells (BM MNCs) secrete TGFβ1 in response to erythropoietin (EPO). We further show that human bone marrow-derived mesenchymal stromal cells (BMSCs) briefly exposed to the conditioned medium of EPO-primed MNCs, or purified TGFβ1, gain significantly increased hematopoiesis-supportive ability. Mechanistically, we show that this phenomenon involves TGFβ1-mediated activation of nitric oxide (NO) signalling pathway in the BMSCs. The data suggest that EPO-MNC-TGFβ1 could be one of the regulatory axes operative in the bone marrow microenvironment involved in maintaining the functionality of the resident BMSCs.
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Affiliation(s)
- Vaijayanti P Kale
- Symbiosis Centre for Stem Cell Research, Symbiosis International University, Pune, India
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Vyas C, Mishbak H, Cooper G, Peach C, Pereira RF, Bartolo P. Biological perspectives and current biofabrication strategies in osteochondral tissue engineering. ACTA ACUST UNITED AC 2020. [DOI: 10.1007/s40898-020-00008-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AbstractArticular cartilage and the underlying subchondral bone are crucial in human movement and when damaged through disease or trauma impacts severely on quality of life. Cartilage has a limited regenerative capacity due to its avascular composition and current therapeutic interventions have limited efficacy. With a rapidly ageing population globally, the numbers of patients requiring therapy for osteochondral disorders is rising, leading to increasing pressures on healthcare systems. Research into novel therapies using tissue engineering has become a priority. However, rational design of biomimetic and clinically effective tissue constructs requires basic understanding of osteochondral biological composition, structure, and mechanical properties. Furthermore, consideration of material design, scaffold architecture, and biofabrication strategies, is needed to assist in the development of tissue engineering therapies enabling successful translation into the clinical arena. This review provides a starting point for any researcher investigating tissue engineering for osteochondral applications. An overview of biological properties of osteochondral tissue, current clinical practices, the role of tissue engineering and biofabrication, and key challenges associated with new treatments is provided. Developing precisely engineered tissue constructs with mechanical and phenotypic stability is the goal. Future work should focus on multi-stimulatory environments, long-term studies to determine phenotypic alterations and tissue formation, and the development of novel bioreactor systems that can more accurately resemble the in vivo environment.
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Silva AN, Lim WAJ, Cheok JWG, Gatot C, Tan HCA. Autologous collagen-induced chondrogenesis versus microfracture for chondral defects of the knee: Surgical technique and 2-year comparison outcome study. J Orthop 2020; 22:294-299. [PMID: 32616991 DOI: 10.1016/j.jor.2020.06.008] [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: 05/31/2020] [Accepted: 06/06/2020] [Indexed: 10/24/2022] Open
Abstract
Objective Osteochondral lesions of the knee affect patients from all age groups with arthroscopic microfracture being the current gold standard of treatment of such lesions. Autologous collagen-induced chondrogenesis (ACIC) is a novel procedure that has recently been gaining popularity. This study aims to compare the 6 and 24 month post-operative outcomes between patients undergoing microfracture only and microfracture with ACIC. Methods Patients from both groups were assessed pre-operatively, at 6 and 24 months post-operatively for functional outcomes using SF-36 and IKDC scoring (International Knee Documentation Committee Subjective Knee Form). Results Both groups showed improved SF-36 and IKDC scores at 6 and 24 months, however patients who underwent ACIC showed better SF-36 mental component and IKDC scores 24 months after surgery. Conclusion This demonstrates that ACIC is an effective, single-stage, joint-preserving procedure which is comparable, if not better, in treating chondral defects.
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Affiliation(s)
- Amila N Silva
- Singapore General Hospital, Outram Road, 169608, Singapore
| | | | | | - Cheryl Gatot
- Singapore General Hospital, Outram Road, 169608, Singapore
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Kouroupis D, Ahari AF, Correa D, Shammaa R. Intralesional Injection of Bone Marrow Aspirate Concentrate for the Treatment of Osteonecrosis of the Knee Secondary to Systemic Lupus Erythematosus: A Case Report. Front Bioeng Biotechnol 2020; 8:202. [PMID: 32266233 PMCID: PMC7100546 DOI: 10.3389/fbioe.2020.00202] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 03/02/2020] [Indexed: 01/08/2023] Open
Abstract
Case: An 18-year-old female patient with Systemic Lupus Erythematosus (SLE) and corticosteroid-associated extensive bilateral symptomatic knee Osteonecrosis (ON) (Ficat IV), treated with sequential intralesional injections of autologous bone marrow aspirate concentrate (BMAC) under ultrasound guidance. At 3 months, pain was almost absent (VAS) and KOOS/WOMAC showed significant improvement sustained up to 24 months. At 12 months MRI indicated bone maturation, significantly reduced BM edema and subchondral fluid volume, and no collapse/fragmentation signs. Discussion: The clinical and imaging significant improvement observed in this patient suggests that BMAC intralesional injections effectively restored the compromised bone structure. After larger studies, this technique can become an alternative to decompressing surgery for ON cases.
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Affiliation(s)
- Dimitrios Kouroupis
- Department of Orthopaedics, UHealth Sports Medicine Institute, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Amir F Ahari
- Canadian Centers for Regenerative Therapy, Toronto, ON, Canada
| | - Diego Correa
- Department of Orthopaedics, UHealth Sports Medicine Institute, University of Miami Miller School of Medicine, Miami, FL, United States.,Diabetes Research Institute & Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Riam Shammaa
- Canadian Centers for Regenerative Therapy, Toronto, ON, Canada.,Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
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Diederichs S, Richter W. Stammzelltherapie. ARTHROSKOPIE 2020. [DOI: 10.1007/s00142-020-00345-7] [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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Desai MJ, Mansfield JT, Robinson DM, Miller BC, Borg-Stein J. Regenerative Medicine for Axial and Radicular Spine-Related Pain: A Narrative Review. Pain Pract 2020; 20:437-453. [PMID: 31869517 DOI: 10.1111/papr.12868] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 11/03/2019] [Accepted: 12/16/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Regenerative injection-based therapy has established itself as a therapeutic option for the management of a variety of painful musculoskeletal conditions. The aim of this work was to review the current literature regarding regenerative injection therapy for axial/radicular spine pain. METHODS A comprehensive literature review was conducted on the use of regenerative medicine for axial/radicular spine pain. Eligible articles analyzed the therapeutic injection effects of platelet-rich plasma (PRP), prolotherapy, or mesenchymal signaling cells (MSCs) via intradiscal, facet joint, epidural, or sacroiliac joint delivery. RESULTS Regarding intradiscal PRP, there are level I/IV studies supporting its use. Regarding intradiscal prolotherapy, there are level III to IV studies supporting its use. Regarding intradiscal MSCs, there are level I/IV studies supporting its use with the exception of one level IV study that found no significant improvement at 12 months. Regarding facet joint injections with PRP, there are level I/IV studies supporting its use. Regarding facet joint injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate any statistical significance supporting its use. Regarding epidural injections with PRP, there are level I/IV studies supporting its use. Regarding epidural injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate statistical significance beyond 48 hours. Regarding sacroiliac joint injections with PRP, there are level I/IV studies supporting its use. Regarding sacroiliac joint injections with prolotherapy, there are level I/III studies supporting its use. CONCLUSIONS Currently, there are level I studies to support the use of PRP and MSC injections for discogenic pain; facet joint injections with PRP; epidural injections of autologous conditioned serum and epidural prolotherapy; and PRP and prolotherapy for sacroiliac joint pain. One level I study showed that facet joint prolotherapy has no significant benefit. Notably, no intervention has multiple published level I studies.
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Affiliation(s)
- Mehul J Desai
- International Spine, Pain & Performance Center, Washington, DC, U.S.A.,George Washington University, Washington, DC, U.S.A.,Division of Pain Medicine, Virginia Hospital Center, Arlington, Virginia, U.S.A
| | - John Taylor Mansfield
- Department of Physical Medicine and Rehabilitation, MedStar Georgetown University Hospital, Washington, DC, U.S.A
| | - David M Robinson
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, U.S.A
| | - Benjamin C Miller
- Department of Physical Medicine and Rehabilitation, MedStar Georgetown University Hospital, Washington, DC, U.S.A
| | - Joanne Borg-Stein
- Division of Sports and Musculoskeletal Rehabilitation, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, U.S.A
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31
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Cotter EJ, Frank RM, Mandelbaum B. Management of osteoarthritis - biological approaches: current concepts. J ISAKOS 2020. [DOI: 10.1136/jisakos-2019-000377] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Melville JC, Mañón VA, Blackburn C, Young S. Current Methods of Maxillofacial Tissue Engineering. Oral Maxillofac Surg Clin North Am 2019; 31:579-591. [DOI: 10.1016/j.coms.2019.07.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Abstract
Use of orthobiologics in sports medicine and musculoskeletal surgery has gained significant interest. However, many of the commercially available and advertised products are lacking in clinical evidence. Widespread use of products before fully understanding their true indications may result in unknown adverse outcomes and may also lead to increased health care costs. As more products become available, it is important to remain judicial in use and to practice evidence-based medicine. Likewise, it is important to continue advances in research in hopes to improve surgical outcomes. This article reviews clinical evidence behind common orthobiologics in the treatment of foot and ankle pathology.
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Cavinatto L, Hinckel BB, Tomlinson RE, Gupta S, Farr J, Bartolozzi AR. The Role of Bone Marrow Aspirate Concentrate for the Treatment of Focal Chondral Lesions of the Knee: A Systematic Review and Critical Analysis of Animal and Clinical Studies. Arthroscopy 2019; 35:1860-1877. [PMID: 30871903 DOI: 10.1016/j.arthro.2018.11.073] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 11/08/2018] [Accepted: 11/22/2018] [Indexed: 02/02/2023]
Abstract
PURPOSE To summarize currently available data regarding the use of bone marrow aspirate concentrate (BMAC) for the treatment of focal chondral lesions of the knee in experimental animal models and human clinical studies. METHODS A systematic review searching for the terms "(bone marrow)" AND "(aspirate OR concentrate)" AND "(cartilage OR chondral OR osteochondral)" was performed in the databases PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar regarding the use of BMAC for the treatment of focal chondral lesions of the knee. The inclusion criteria were animal and clinical studies published in English that used autologous BMAC to treat focal chondral defects of the knee. We excluded studies that evaluated nonconcentrated preparations of bone marrow aspirate or preparations that were culture expanded. RESULTS A total of 23 studies were included: 10 studies performed in animal models and 13 human clinical studies. Animal studies showed inconsistent outcomes regarding the efficacy of BMAC for the treatment of chondral or osteochondral lesions, assessed by gross morphology, second-look arthroscopy, magnetic resonance imaging, histology, immunohistochemistry, mechanical testing, and micro-tomography. Chondral defect filling was achieved with fibrocartilage or "hyaline-like" cartilage. Cells present in BMAC did not meet the criteria to be characterized as mesenchymal stem cells according to the International Society for Cell Therapy because freshly isolated cells failed to show tri-lineage differentiation. Overall, all clinical studies, independent of the study group or level of evidence, reported improved clinical outcomes and higher macroscopic, magnetic resonance imaging, and histology scores. Comparative trials favored BMAC over microfracture and reported equivalent outcomes between BMAC and matrix-induced autologous chondrocyte implantation. However, clinical studies were scant and showed low scientific rigor, poor methodologic quality, and low levels of evidence on average. CONCLUSIONS Although clinical success in short-term and midterm applications has been suggested for the application of BMAC for the restoration of cartilage defects in lesions of the knee, current study designs are generally of low scientific rigor. In addition, clinical applications of this technology in animal model investigations have shown inconsistent outcomes. Thus, clinicians should apply this technology cautiously. LEVEL OF EVIDENCE Level IV, systematic review of Level II, III, and IV evidence studies.
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Affiliation(s)
| | | | | | - Sunny Gupta
- Jefferson 3B Orthopaedics, Philadelphia, Pennsylvania, U.S.A
| | - Jack Farr
- Cartilage Restoration Center, OrthoIndy, Greenwood, Indiana, U.S.A
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Koch M, Hammer S, Fuellerer J, Lang S, Pfeifer CG, Pattappa G, Weber J, Loibl M, Nerlich M, Angele P, Zellner J. Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure-Evaluation of an In Vivo Model. Int J Mol Sci 2019; 20:ijms20051120. [PMID: 30841560 PMCID: PMC6429139 DOI: 10.3390/ijms20051120] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 02/25/2019] [Accepted: 02/26/2019] [Indexed: 12/11/2022] Open
Abstract
Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure.
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Affiliation(s)
- Matthias Koch
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Selma Hammer
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Julian Fuellerer
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Siegmund Lang
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Christian G Pfeifer
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Girish Pattappa
- Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Johannes Weber
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Markus Loibl
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Michael Nerlich
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
| | - Peter Angele
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
- Sporthopaedicum Regensburg/Straubing, Hildegard-von-Bingen-Str. 1, 93053, Regensburg, Germany.
| | - Johannes Zellner
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
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Autologous bone marrow-derived cells for venous leg ulcers treatment: a pilot study. Cytotherapy 2019; 21:189-199. [PMID: 30700393 DOI: 10.1016/j.jcyt.2019.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/30/2018] [Accepted: 01/08/2019] [Indexed: 01/17/2023]
Abstract
BACKGROUND Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow-derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds. Our objective was to evaluate feasibility, safety and initial clinical outcome of autologous BMDC therapy associated with standard treatment in patients with VLUs. METHODS We conducted an open-label, single-arm, prospective pilot clinical trial in four patients with six chronic VLUs. The study protocol was approved by the institutional and national review boards and ethics committees. Bone marrow was harvest, processed and then administered by multiple injections into the ulcers. All patients received standard treatment and non-healing characteristics of the VLUs were confirmed at study entry. RESULTS Ulcer size and wound pain evaluated 12 months after BMDC treatment were significantly reduced (P < 0.05). BMDC treatment was safe and well tolerated in long-term follow-up. DISCUSSION Despite the low number of patients studied, our results showed that autologous BMDC treatment could be a useful, feasible and safe procedure to enhance ulcer healing. However, randomized controlled trials with more patients are needed to address this question and translate this approach into clinical practice.
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Leong NL, Redondo M, Christian D, Yanke AB, Cole BJ. Biologic Injections in the Treatment of Cartilage Defects. OPER TECHN SPORT MED 2018. [DOI: 10.1053/j.otsm.2018.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Rackwitz L, Reichert JC, Haversath M, Nöth U, Jäger M. [Cell-based and future therapeutic strategies for femoral head necrosis]. DER ORTHOPADE 2018; 47:770-776. [PMID: 30143825 DOI: 10.1007/s00132-018-3619-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The application of cell- and growth factor-based techniques in conjunction with conventional surgical approaches has great therapeutic potential for the treatment of avascular necrosis of the femoral head (AVNFH). OBJECTIVES This review provides an overview of new strategies for the treatment of AVNFH, with emphasis on cell and growth factor-based approaches. MATERIALS AND METHODS The results of a literature search are summarised, the most relevant publications are presented and discussed by the authors. RESULTS In the focus of new strategies for treatment of AVNFH are bone marrow-derived cell concentrates and ex vivo-expanded mesenchymal stem cells. Besides local application during core decompression, the systemic administration of cells via blood vessels supplying the femoral head is an interesting approach. The application of osteogenic and angiogenic growth factor-laden scaffold materials has also been clinically tested. Initial results of randomised clinical trials using cell- and growth factor-based approaches underline the potential of these innovative therapeutic strategies. Cell-based therapies are governed by EU law and generally require a manufacturing authorization. CONCLUSION To date, only few randomized controlled clinical trials are available which additionally display a considerable diversity concerning cell parameters, cell processing, adjuvant surgical techniques and the quality outcome parameters. Therefore, a final statement about the effectiveness of new cell and growth factor-based strategies is currently not possible.
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Affiliation(s)
- L Rackwitz
- Klinik für Orthopädie und Unfallchirurgie, Evangelisches Waldkrankenhaus Spandau, Stadtrandstraße 555, 13589, Berlin, Deutschland.
| | - J C Reichert
- Klinik für Orthopädie und Unfallchirurgie, Evangelisches Waldkrankenhaus Spandau, Stadtrandstraße 555, 13589, Berlin, Deutschland
| | - M Haversath
- Klinik für Orthopädie und Unfallchirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - U Nöth
- Klinik für Orthopädie und Unfallchirurgie, Evangelisches Waldkrankenhaus Spandau, Stadtrandstraße 555, 13589, Berlin, Deutschland
| | - M Jäger
- Klinik für Orthopädie und Unfallchirurgie, Universitätsklinikum Essen, Essen, Deutschland
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Early Clinical Outcomes of Intra-Articular Injections of Bone Marrow Aspirate Concentrate for the Treatment of Early Osteoarthritis of the Hip and Knee: A Cohort Study. PM R 2018; 10:1353-1359. [PMID: 29857166 DOI: 10.1016/j.pmrj.2018.05.016] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 04/21/2018] [Accepted: 05/13/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Bone marrow aspirate concentrate (BMC) is one of the few cell-based therapies available as a possible biological treatment for early osteoarthritis (OA). Its efficacy, safety, and benefit compared with other treatments are still to be determined. OBJECTIVE To assess the clinical outcomes of patients undergoing intra-articular injection of BMC for the treatment of early knee and hip OA. DESIGN Prospective, cohort study. SETTING Single institution, quaternary level of care. PATIENTS Nineteen patients (16 female and 3 male), totaling 25 joints (10 knees, 15 hips), treated with intra-articular BMC for early OA between 2014 and 2016. The mean age at time of the procedure was 58 ± 12.7 years (range, 30-80 years). The mean follow-up was 13.2 ± 6.3 months (range, 6-24 months). Inclusion criteria included ≥18 years; knee OA, Kellgren-Lawrence grade I-II; hip OA, Tönnis grade I-II; first-time intra-articular BMC therapy, after unsuccessful symptomatic and conservative treatments (ie, physical therapy, analgesics and anti-inflammatory drugs) for 6 months. Exclusion criteria included pregnancy; malignancy; rheumatologic diseases; infection; Kellgren-Lawrence grade III-IV; Tönnis grade III; and previous intra-articular injections or surgery. INTERVENTIONS All patients had autologous bone marrow aspirate harvested from the iliac crest and centrifuged to achieve BMC, for intra-articular injection. MAIN OUTCOME MEASUREMENTS The hypothesis was formulated before the study. Patient-reported outcomes measures were assessed preoperatively and at last follow-up using the Western Ontario and McMaster Universities Arthritis Index. RESULTS Western Ontario and McMaster Universities Arthritis Index improved from a baseline of 40.8 ± 18.3% to 20.6 ± 17% (P < .001) at final follow-up. The satisfaction rate was 63.2%. The minimal clinically important difference threshold of 9.15 points was reached by 64% of the patients. Two patients were converted to total hip arthroplasty at 8 months after BMC injection. CONCLUSIONS Intra-articular injections of BMC for the treatment of early knee or hip OA were safe and demonstrated satisfactory results in 63.2% of patients. Future studies are necessary to determine the efficacy of this technique and its safety profile. LEVEL OF EVIDENCE II.
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Abstract
Purpose of Review This review provides an overview of well-established and newly developed cartilage repair techniques for cartilage defects in the patellofemoral joint (PFJ). An algorithm will be presented for approaching cartilage defects considering the distinct anatomy of both the patellar and trochlear articular surfaces. Recent Findings Recent studies on cartilage repair in the PFJ have demonstrated improved outcomes in an attempt to delay or obviate the need for arthroplasty, and improve symptoms in young patients. While autologous chondrocyte implantation shows good and excellent outcomes for chondral lesions, osteochondral defects are adequately addressed with osteochondral allograft transplantation. In case of patellar malalignment, concomitant tibial tubercle osteotomy can significantly improve outcomes. Particulated cartilage and bone marrow aspirate concentrate are potential new alternative treatments for cartilage repair, currently in early clinical studies. Summary Due to the frequency of concomitant anatomic abnormalities in the PFJ, a thorough clinical examination combined with careful indication for each procedure in each individual patient combined with meticulous surgical technique is central to achieve satisfying outcomes. Additional comparative studies of cartilage repair procedures, as well as investigation of newer techniques, are needed.
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Cotter EJ, Wang KC, Yanke AB, Chubinskaya S. Bone Marrow Aspirate Concentrate for Cartilage Defects of the Knee: From Bench to Bedside Evidence. Cartilage 2018; 9:161-170. [PMID: 29126349 PMCID: PMC5871125 DOI: 10.1177/1947603517741169] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including ["bone marrow aspirate" and "cartilage"], ["mesenchymal stem cells" and "cartilage"], and ["bone marrow aspirate" and "mesenchymal stem cells" and "orthopedics"]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived-mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.
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Affiliation(s)
- Eric J. Cotter
- Georgetown University School of Medicine, Washington, DC, USA
| | - Kevin C. Wang
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, USA
| | - Adam B. Yanke
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, USA
| | - Susan Chubinskaya
- Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA
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El-Jawhari JJ, Brockett CL, Ktistakis I, Jones E, Giannoudis PV. The regenerative therapies of the ankle degeneration: a focus on multipotential mesenchymal stromal cells. Regen Med 2018; 13:175-188. [PMID: 29553890 DOI: 10.2217/rme-2017-0104] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The ankle degeneration ranging from focal osteochondral lesions to osteoarthritis can cause a total joint function loss. With rising life expectancy and activity of the patients, various regenerative therapies were introduced aiming to preserve the joint function via the induction of cartilage and bone repair. Here, biological events and mechanical changes of the ankle degeneration were discussed. The regenerative therapies were reviewed versus the standard surgical treatment. We especially focused on the use of mesenchymal (multipotential) stromal cells (MSCs) highlighting their dual functions of regeneration and cell modulation with an emphasis on the emerging MSC-based clinical studies. Being at an early step, more basic and clinical research is needed to optimize the applications of all ankle regenerative therapies including MSC-based methods.
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Affiliation(s)
- Jehan J El-Jawhari
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Clinical pathology department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Claire L Brockett
- Institute of Medical & Biological Engineering, University of Leeds, Leeds, UK
| | - Ioannis Ktistakis
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Academic Unit of Trauma and Orthopaedic Surgery, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Elena Jones
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Peter V Giannoudis
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Academic Unit of Trauma and Orthopaedic Surgery, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Whitney KE, Liebowitz A, Bolia IK, Chahla J, Ravuri S, Evans TA, Philippon MJ, Huard J. Current perspectives on biological approaches for osteoarthritis. Ann N Y Acad Sci 2018; 1410:26-43. [PMID: 29265418 DOI: 10.1111/nyas.13554] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Revised: 10/18/2017] [Accepted: 10/25/2017] [Indexed: 12/18/2022]
Abstract
Musculoskeletal injuries that disrupt the structure and function of diarthrodial joints can cause permanent biomechanical alterations and lead to a more severe, chronic condition. Despite advancements that have been made to restore tissue function and delay the need for joint replacement, there are currently no disease-modifying therapies for osteoarthritis (OA). To reduce the risk of OA, innovative preventive medicine approaches have been developed over the last decade to treat the underlying pathology. Several biological approaches are promising treatment modalities for various stages of OA owing to their minimally invasive nature and actively dynamic physiological mechanisms that attenuate tissue degradation and inflammatory responses. Individualized growth factor and cytokine therapies, tissue-engineered biomaterials, and cell-based therapies have revolutionary potential for orthopedic applications; however, the paucity of standardization and categorization of biological components and their counterparts has made it difficult to determine their clinical and biological efficacy. Cell-based therapies and tissue-engineered biologics have become lucrative in sports medicine and orthopedics; nonetheless, there is a continued effort to produce a biological treatment modality tailored to target intra-articular structures that recapitulates tissue function. Advanced development of these biological treatment modalities will potentially optimize tissue healing, regeneration, and joint preservation strategies. Therefore, the purpose of this paper is to review current concepts on several biological treatment approaches for OA.
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Affiliation(s)
- Kaitlyn E Whitney
- Steadman Philippon Research Institute, Vail, Colorado.,The Steadman Clinic, Vail, Colorado
| | | | | | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado
| | | | - Thos A Evans
- Steadman Philippon Research Institute, Vail, Colorado.,The Steadman Clinic, Vail, Colorado
| | - Marc J Philippon
- Steadman Philippon Research Institute, Vail, Colorado.,The Steadman Clinic, Vail, Colorado
| | - Johnny Huard
- Steadman Philippon Research Institute, Vail, Colorado.,The University of Texas Health Science Center at Houston, Houston, Texas
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46
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Abstract
BACKGROUND Cell and growth factor based strategies bear great potential to support the healing processes in cartilage repair and the therapy of osteoarthritic joints. OBJECTIVES The following review provides an overview of novel experimental strategies for the therapy of focal cartilage defects and osteoarthritis, with emphasis on cell and growth factor based approaches. MATERIALS AND METHODS The authors summarize their own data regarding the intraarticular injection of stem cells to treat osteoarthritis of the knee and provide a synopsis of the available literature discussing the most significant publications. RESULTS The development of novel strategies for the treatment of focal and arthrotic cartilage lesions focuses on the application of growth factors, platelet rich plasma (PRP), bone marrow (BMSAC) or adipose derived (stromal vascular fraction - SVF) cell concentrates, and ex vivo expanded mesenchymal stem cells (MSC). First clinical data on the use of expanded MSCs show the potential of this innovative therapeutic strategy. These approaches, however, are governed by EU law and often require approval by regulatory bodies. CONCLUSION Currently, only a limited number of published, randomized, controlled trials available. Therefore, it is not possible to finally assess the efficacy of these strategies at this point in time.
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Imam MA, Holton J, Horriat S, Negida AS, Grubhofer F, Gupta R, Narvani A, Snow M. A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in tendon pathology. SICOT J 2017; 3:58. [PMID: 28990575 PMCID: PMC5632955 DOI: 10.1051/sicotj/2017039] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 07/04/2017] [Indexed: 12/24/2022] Open
Abstract
Tendon pathologies are a group of musculoskeletal conditions frequently seen in clinical practice. They can be broadly classified into traumatic, degenerative and overuse-related tendinopathies. Rotator cuff tears, Achilles tendinopathy and tennis elbow are common examples of these conditions. Conventional treatments have shown inconsistent outcomes and might fail to provide satisfactory clinical improvement. With the growing trend towards the use of mesenchymal stem cells (MSCs) in other branches of medicine, there is an increasing interest in treating tendon pathologies using the bone marrow MSC. In this article, we provide a systematic literature review documenting the current status of the use of bone marrow aspirate concentrate (BMAC) for the treatment of tendon pathologies. We also asked the question on the safety of BMAC and whether there are potential complications associated with BMAC therapy. Our hypothesis is that the use of BMAC provides safe clinical benefit when used for the treatment of tendinopathy or as a biological augmentation of tendon repair. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist while preparing this systematic review. A literature search was carried out including the online databases of PubMed, EMBASE, ClinicalTrial.gov and the Cochrane Library from 1960 to the end of May 2015. Relevant studies were selected and critically appraised. Data from eligible studies were extracted and classified per type of tendon pathology. We included 37 articles discussing the application and use of BMAC for the treatment of tendon pathologies. The Critical Appraisal Skills Program (CASP) appraisal confirmed a satisfactory standard of 37 studies. Studies were sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (n = 18), where five studies looked at the evaluation of aspiration techniques (n = 5), augmentation of rotator cuff tears (n = 5), augmentation of tendo-achilles tendon (n = 1), treatment of gluteal tendon injuries (n = 1), management of elbow epicondylitis (n = 2), management of patellar tendinopathy (n = 1) and complications related to BMAC (n = 5). Multiple experimental studies investigated the use of BMAC for tendon repair; nonetheless, there are only limited clinical studies available in this field. Unfortunately, due to the scarcity of studies, which were mainly case series, the current level of evidence is weak. We strongly recommend further future randomised controlled studies in this field to allow scientists and clinicians make evidence-based conclusions.
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Affiliation(s)
- Mohamed A. Imam
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Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University Circular road Ismailia
41111 Egypt
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The Royal Orthopaedic Hospital Birmingham
B31 2AP UK
| | - James Holton
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The Royal Orthopaedic Hospital Birmingham
B31 2AP UK
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Birmingham University Birmingham
B15 2TT UK
| | | | | | - Florian Grubhofer
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Department of Orthopaedics, Balgrist University Hospital, University of Zurich Forchstrasse 340 8008
Zürich Switzerland
| | - Rohit Gupta
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Ashford and St Peters Hospitals Chertsey
KT16 0PZ UK
| | - Ali Narvani
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Ashford and St Peters Hospitals Chertsey
KT16 0PZ UK
| | - Martyn Snow
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The Royal Orthopaedic Hospital Birmingham
B31 2AP UK
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Regenerative Medicine, Aston University, Aston Triangle Birmingham
B4 7ET UK
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Oladeji LO, Stannard JP, Cook CR, Kfuri M, Crist BD, Smith MJ, Cook JL. Effects of Autogenous Bone Marrow Aspirate Concentrate on Radiographic Integration of Femoral Condylar Osteochondral Allografts. Am J Sports Med 2017; 45:2797-2803. [PMID: 28737949 DOI: 10.1177/0363546517715725] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Transplantation of fresh osteochondral allografts (OCAs) is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Because the lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. PURPOSE To determine if autogenous bone marrow aspirate concentrate (BMC) treatment of large femoral condylar OCAs would be associated with superior radiographic OCA bone integration compared with nontreated allografts during the critical first 6 months after surgery. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS A review of patients enrolled in a prospective registry who were treated with transplantation of large OCAs to one or both femoral condyles at our institution from March 12, 2013 to March 14, 2016 was performed. Patients were stratified into 2 groups based on BMC treatment versus no BMC treatment; the treatment was nonrandomized and was rooted in a shift in practice and a continuing effort to optimize OCA transplantation at our institution. Patients were excluded if they did not have orthogonal view radiographs performed at 6 weeks, 3 months, and 6 months postoperatively. Each condyle undergoing OCA transplantation was assessed individually by an independent musculoskeletal radiologist, who was blinded to the treatment group and time point. OCAs were assessed with respect to graft integration (0%-100%; 0 = no integration, 100 = complete integration) and degree of sclerosis (0-3; 0 = normal, 1 = mild sclerosis, 2 = moderate sclerosis, and 3 = severe sclerosis) of the graft at each time point. RESULTS This study identified 17 condyles in 15 patients who underwent OCA transplantation without BMC and 29 condyles in 22 patients who underwent OCA transplantation with BMC. The BMC group had significantly ( P = .033) higher graft integration scores at 6 weeks, 3 months, and 6 months after surgery. Graft sclerosis was significantly ( P = .017) less in the BMC group at 6 weeks and 3 months, with no significant difference at 6 months after surgery. When combining the groups to examine the influence of smoking on graft integration, nonsmokers had significantly ( P = .007) higher graft integration scores at 6 months. CONCLUSION Large femoral condylar OCAs treated with autogenous BMC before implantation showed superior radiographic integration to bone and less sclerosis during the initial 6-month postoperative period. BMC treatment of OCAs may mitigate the failure of OCA bone healing.
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Affiliation(s)
- Lasun O Oladeji
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - James P Stannard
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA.,Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri, USA
| | - Cristi R Cook
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA.,Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri, USA
| | - Mauricio Kfuri
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - Brett D Crist
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - Matthew J Smith
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - James L Cook
- Department of Orthopaedic Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA.,Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri, USA
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49
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Murphy MP, Buckley C, Sugrue C, Carr E, O'Reilly A, O'Neill S, Carroll SM. ASCOT: Autologous Bone Marrow Stem Cell Use for Osteoarthritis of the Thumb-First Carpometacarpal Joint. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2017; 5:e1486. [PMID: 29062653 PMCID: PMC5640358 DOI: 10.1097/gox.0000000000001486] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 07/19/2017] [Indexed: 12/19/2022]
Abstract
Background: The first carpometacarpal joint (CMCJ) in the hand is a commonly affected joint by osteoarthritis. It causes significant thumb base pain, limiting functional capacity. Microfracturing and application of autologous stem cells has been performed on large joints such as the knee but has never been evaluated for use in the smaller joints in the hand. Our aim was to determine the potential benefit of microfracturing and autologous bone marrow stem cells for treatment of osteoarthritis of the first CMCJ in the hand. Methods: All inclusion criteria were satisfied. Preoperative assessment by the surgeon, physiotherapist, and occupational therapist was performed. The first CMCJ was microfractured and the Bone Marrow Stem Cells were applied directly. Postoperatively, the patients were followed up for 1 year. Results: Fifteen patients met inclusion criteria; however, 2 patients were excluded due to postoperative cellulitis and diagnosis of De Quervain's tenosynovitis. The mean scores of the 13-patient preoperative and 1 year follow-up assessments are visual analog score at rest of 3.23–1.69 (P = 0.0292), visual analog score on activity of 7.92–4.23 (P = 0.0019), range of motion 45.77o–55.15o (P = 0.0195), thumb opposition score 7.62–9.23 (P = 0.0154), Disability of the Arm, Shoulder and Hand score of 51.67–23.08 (P = 0.0065). Strength improved insignificantly from 4.7 kg preoperatively to 5.53 kg at 12 months (P = 0.1257). All patients had a positive Grind test preoperatively and a negative test after 12 months. Conclusions: This innovative pilot study is a new approach to osteoarthritis of the thumb.
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Affiliation(s)
- Matthew P Murphy
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
| | - Christina Buckley
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
| | - Conor Sugrue
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
| | - Emma Carr
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
| | - Aine O'Reilly
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
| | - Shane O'Neill
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
| | - Sean M Carroll
- Department of Plastic Surgery, Saint Vincent's University Hospital, Dublin, Ireland
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Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects. Stem Cells Int 2017; 2017:1609685. [PMID: 28607559 PMCID: PMC5451778 DOI: 10.1155/2017/1609685] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 03/15/2017] [Accepted: 04/12/2017] [Indexed: 12/20/2022] Open
Abstract
Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed.
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