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Fontana G, Nemke B, Lu Y, Chamberlain C, Lee JS, Choe JA, Jiao H, Nelson M, Amitrano M, Li WJ, Markel M, Murphy WL. Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects. Bioact Mater 2025; 45:509-519. [PMID: 39717366 PMCID: PMC11665573 DOI: 10.1016/j.bioactmat.2024.11.033] [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: 09/23/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 12/25/2024] Open
Abstract
Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair. We used mineral-coated microparticles to deliver TGF-β1 mRNA to autologous BMAC. mRNA-activated BMAC was suspended in peripheral blood to generate therapeutic BMAC clots, which were then implanted in rabbit osteochondral defects. Tracking studies revealed that the clots were reliably maintained in the defects for at least 2 weeks. TGF-β1 mRNA delivery significantly increased TGF-β1 production in BMAC clots and increased early expression of articular chondrocyte markers within osteochondral defects. At 9 weeks post-surgery, the mRNA-treated defects had a superior macroscopic cartilage appearance, decreased type I collagen deposition, increased stain intensity for type II collagen and increased glycosaminoglycan deposition area when compared to the controls. Despite the transient expression of therapeutic mRNA we have detected lasting effects, such as a decrease in fibrocartilage formation demonstrated by the decrease in type I collagen deposition and the improvement in macroscopic appearance in the treatment group.
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Affiliation(s)
| | | | - Yan Lu
- School of Veterinary Medicine, USA
| | | | - Jae-Sung Lee
- Department of Orthopedics and Rehabilitation, USA
| | | | - Hongli Jiao
- Department of Orthopedics and Rehabilitation, USA
| | | | | | - Wan-Ju Li
- Department of Orthopedics and Rehabilitation, USA
| | | | - William L. Murphy
- Department of Orthopedics and Rehabilitation, USA
- Department of Biomedical Engineering, USA
- Material Sciences and Engineering, University of Wisconsin-Madison, Madison, WI, USA
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Thomas VJ, Buchweitz NF, Wu Y, Mercuri JJ. Evaluation of Cartilage-Like Matrix Formation in a Nucleus Pulposus-Derived Cartilage Analog Scaffold. J Biomed Mater Res B Appl Biomater 2025; 113:e35534. [PMID: 39797498 DOI: 10.1002/jbm.b.35534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 11/21/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025]
Abstract
The formation of fibrocartilage in microfracture (MFX) severely limits its long-term outlook. There is consensus in the scientific community that the placement of an appropriate scaffold in the MFX defect site can promote hyaline cartilage formation and improve therapeutic benefit. Accordingly, in this work, a novel natural biomaterial-the cartilage analog (CA)-which met criteria favorable for chondrogenesis, was evaluated in vitro to determine its candidacy as a potential MFX scaffold. Human bone marrow stem cells (hBMSCs) were seeded onto the CA and cultured for 28 days in chondrogenic differentiation media. Sulfated glycosaminoglycan (sGAG) and hydroxyproline (HYP) contents were significantly higher than their non-seeded counterparts on both Days 14 and 28 (average sGAG on Day 28: 73.26 vs. 23.82 μg/mg dry wt. of tissue; average HYP on Day 28: 56.19 vs. 38.80 ± 2.53 μg/mg dry wt. of tissue). Histological assessments showed cellular infiltration and abundant sGAG formation for seeded CAs at both time points with new cartilage-like matrix filling up its laser-drilled channels. Polarized light microscopy of picrosirius red stained samples showed collagen fibrils aligning along the path of the laser-drilled channels. However, the seeded scaffolds were also found to have contracted by 20% by the end of the study with their average aggregate moduli significantly lower than non-seeded controls (10.52 vs. 21.74 kPa). Nevertheless, the CA was ultimately found to support the formation of a cartilage-like matrix, and therefore, merits consideration as a scaffold of interest for improving MFX.
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Affiliation(s)
- Vishal Joseph Thomas
- The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA
| | - Nathan Foster Buchweitz
- The Orthopaedic Bioengineering Laboratory, Department of Bioengineering, Clemson University, Charleston, South Carolina, USA
| | - Yongren Wu
- The Orthopaedic Bioengineering Laboratory, Department of Bioengineering, Clemson University, Charleston, South Carolina, USA
| | - Jeremy John Mercuri
- The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA
- The Frank H. Stelling and C. Dayton Riddle Orthopaedic Research and Education Laboratory, Clemson University Biomedical Engineering Innovation Campus, Greenville, South Carolina, USA
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Lana JF, Purita J, Jeyaraman M, de Souza BF, Rodrigues BL, Huber SC, Caliari C, Santos GS, da Fonseca LF, Dallo I, Navani A, De Andrade MAP, Everts PA. Innovative Approaches in Knee Osteoarthritis Treatment: A Comprehensive Review of Bone Marrow-Derived Products. Biomedicines 2024; 12:2812. [PMID: 39767717 PMCID: PMC11672900 DOI: 10.3390/biomedicines12122812] [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: 09/02/2024] [Revised: 11/05/2024] [Accepted: 11/09/2024] [Indexed: 01/06/2025] Open
Abstract
Knee osteoarthritis (OA) is a chronic articular disease characterized by the progressive degeneration of cartilage and bone tissue, leading to the appearance of subchondral cysts, osteophyte formation, and synovial inflammation. Conventional treatments consist of non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and glucocorticoids. However, the prolonged use of these drugs causes adverse effects. NSAIDs, for instance, are known to be nephrotoxic, increasing the damage to articular cartilage. New therapies capable of accelerating the process of tissue regeneration and repair are being discussed, such as the use of orthobiologics that are naturally found in the body and obtained through minimally invasive collection and/or laboratory manipulations. Bone marrow aspirate (BMA) and bone marrow aspirate concentrate (BMAC) are both rich in hematopoietic stem cells, mesenchymal stem cells (MSCs), and growth factors (GFs) that can be used in the healing process due to their anabolic and anti-inflammatory effects. The aim of this literature review is to assess the efficacy of BMA and BMAC in the treatment of knee OA based on the favorable results that researchers have obtained with the use of both orthobiologics envisaging an accelerated healing process and the prevention of OA progression.
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Affiliation(s)
- José Fábio Lana
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (J.P.); (I.D.); (A.N.); (P.A.E.)
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil;
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
- Medical School, Jaguariúna University Center (UniFAJ), Jaguariúna13911-094, SP, Brazil
- Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil
| | - Joseph Purita
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (J.P.); (I.D.); (A.N.); (P.A.E.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
| | - Madhan Jeyaraman
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
- Department of Orthopedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
| | - Bianca Freitas de Souza
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil;
| | - Bruno Lima Rodrigues
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
| | - Stephany Cares Huber
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
| | - Carolina Caliari
- Cell Therapy, In Situ Terapia Celular, Ribeirão Preto 14056-680, SP, Brazil;
| | - Gabriel Silva Santos
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil;
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
| | - Lucas Furtado da Fonseca
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
| | - Ignacio Dallo
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (J.P.); (I.D.); (A.N.); (P.A.E.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
| | - Annu Navani
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (J.P.); (I.D.); (A.N.); (P.A.E.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
- Comprehensive Spine & Sports Center, Campbell, CA 95008, USA
| | | | - Peter Albert Everts
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil; (J.F.L.); (J.P.); (I.D.); (A.N.); (P.A.E.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (M.J.); (B.L.R.); (S.C.H.); (L.F.d.F.)
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Voos JE, Moyal A, Furdock R, Caplan AI, Bonfield TL, Calcei JG. Culture Expansion Alters Human Bone Marrow-Derived Mesenchymal Stem Cell Production of Osteoarthritis-Relevant Cytokines and Growth Factors. Arthroscopy 2024:S0749-8063(24)00875-2. [PMID: 39505158 DOI: 10.1016/j.arthro.2024.10.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 11/08/2024]
Abstract
PURPOSE The purposes of this study were to characterize the human bone marrow-derived mesenchymal stem cells (BM-MSCs) production of osteoarthritis-relevant cytokines and growth factors as they are purified and multiplied, a process termed culture expansion, and to compare the immunomodulatory potential of BM-MSCs based on source and medium used for culture expansion. METHODS BM-MSCs were obtained from iliac crest bone marrow aspirates of 4 healthy donors. These 4 BM-MSC cell lines underwent 4 rounds, or "passages," of the institutional culture expansion protocol, using institutional culture media. The secretory molecules known to play a role in osteoarthritis-related inflammatory immune response, cartilage degradation, and patient symptoms, together called the BM-MSC "secretome," were measured at each passage. Three lines of commercially available BM-MSCs from healthy donors underwent culture expansion by the same protocol, using commercial culture media. The commercial BM-MSCs secretome and the institutional BM-MSCs secretome were compared at each passage. Significance was set at P < .05. RESULTS Institutional BM-MSCs produced less interleukin-6 at passages 3 (237 ± 113 pg/mL) and 4 (237 ± 113 pg/mL) compared with passages 1 (884 ± 97 pg/mL) and 2 (1071 ± 129 pg/mL; P < .01). Institutional BM-MSCs produced more macrophage inflammatory protein 3-alpha at passage 4 than at passage 1 (106 ± 41 vs 32 ± 7 pg/mL; P < .01). Across passages of culture expansion, institutional BM-MSCs grown on institutional medium expressed more interleukin-6 (P < .001), interleukin-10 (P < .001), interleukin-1 beta (P < .001), tumor necrosis factor alpha (P = .004), and vascular endothelial growth factor C (P = .003) than commercially available BM-MSCs grown on commercial medium. CONCLUSIONS Culture expansion alters key molecules within the BM-MSC secretome. Additionally, differences in BM-MSC source and culture medium alter the BM-MSC secretome and its immunomodulatory potential. CLINICAL RELEVANCE This study characterizes the in-vitro changes in BM-MSC secretome during culture expansion based on the cell source and culture medium. It suggests nonequivalence of culture-expanded BM-MSC therapies obtained from different donors using different culture media, even if delivering equivalent numbers of BM-MSCs.
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Affiliation(s)
- James E Voos
- University Hospitals Drusinsky Sports Medicine Institute, Cleveland, Ohio, U.S.A.; Case Western Reserve University School of Medicine (CWRU SOM), CWRU College of Arts and Sciences, Cleveland, Ohio, U.S.A
| | - Andrew Moyal
- University Hospitals Drusinsky Sports Medicine Institute, Cleveland, Ohio, U.S.A.; Case Western Reserve University School of Medicine (CWRU SOM), CWRU College of Arts and Sciences, Cleveland, Ohio, U.S.A..
| | - Ryan Furdock
- University Hospitals Drusinsky Sports Medicine Institute, Cleveland, Ohio, U.S.A.; Case Western Reserve University School of Medicine (CWRU SOM), CWRU College of Arts and Sciences, Cleveland, Ohio, U.S.A
| | - Arnold I Caplan
- Case Western Reserve University School of Medicine (CWRU SOM), CWRU College of Arts and Sciences, Cleveland, Ohio, U.S.A.; Department of Biology, Case Western Reserve University, Cleveland, Ohio, U.S.A.; Skeletal Research Center, Case Western Reserve University, Cleveland, Ohio, U.S.A.; National Center of Regenerative Medicine, Cleveland, Ohio, U.S.A
| | - Tracey L Bonfield
- Case Western Reserve University School of Medicine (CWRU SOM), CWRU College of Arts and Sciences, Cleveland, Ohio, U.S.A.; Department of Biology, Case Western Reserve University, Cleveland, Ohio, U.S.A.; Skeletal Research Center, Case Western Reserve University, Cleveland, Ohio, U.S.A.; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, U.S.A.; National Center of Regenerative Medicine, Cleveland, Ohio, U.S.A
| | - Jacob G Calcei
- University Hospitals Drusinsky Sports Medicine Institute, Cleveland, Ohio, U.S.A.; Case Western Reserve University School of Medicine (CWRU SOM), CWRU College of Arts and Sciences, Cleveland, Ohio, U.S.A
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Muthu S, Viswanathan VK, Sakthivel M, Thabrez M. Does progress in microfracture techniques necessarily translate into clinical effectiveness? World J Orthop 2024; 15:266-284. [PMID: 38596189 PMCID: PMC10999967 DOI: 10.5312/wjo.v15.i3.266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 12/21/2023] [Accepted: 01/23/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Multitudinous advancements have been made to the traditional microfracture (MFx) technique, which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect. The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood. AIM To comparatively analyze the functional, radiological, and histological outcomes, and complications of various generations of MFx available for the treatment of cartilage defects. METHODS A systematic review was performed using PubMed, EMBASE, Web of Science, Cochrane, and Scopus. Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis. We included only randomized controlled trials (RCTs) reporting functional, radiological, histological outcomes or complications of various generations of MFx for the management of cartilage defects. Network meta-analysis (NMA) was conducted in Stata and Cochrane's Confidence in NMA approach was utilized for appraisal of evidence. RESULTS Forty-four RCTs were included in the analysis with patients of mean age of 39.40 (± 9.46) years. Upon comparing the results of the other generations with MFX-I as a constant comparator, we noted a trend towards better pain control and functional outcome (KOOS, IKDC, and Cincinnati scores) at the end of 1-, 2-, and 5-year time points with MFx-III, although the differences were not statistically significant (P > 0.05). We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture (weighted mean difference: 17.44, 95% confidence interval: 0.72, 34.16, P = 0.025; without significant heterogeneity) at 1 year. However, the difference was not maintained at 2 years. There was a trend towards better defect filling on MRI with the second and third generation MFx, although the difference was not statistically significant (P > 0.05). CONCLUSION The higher generations of traditional MFx technique utilizing acellular and cellular components to augment its potential in the management of cartilage defects has shown only marginal improvement in the clinical and radiological outcomes.
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Affiliation(s)
- Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Biotechnology, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College, Karur 639004, Tamil Nadu, India
| | | | - Manoharan Sakthivel
- Department of Orthopaedics, Government Medical College, Karur 639004, Tamil Nadu, India
| | - Mohammed Thabrez
- Department of Medical Oncology, Aster Medcity Hospital, Kochi 682034, India
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Lv Z, Cai X, Bian Y, Wei Z, Zhu W, Zhao X, Weng X. Advances in Mesenchymal Stem Cell Therapy for Osteoarthritis: From Preclinical and Clinical Perspectives. Bioengineering (Basel) 2023; 10:bioengineering10020195. [PMID: 36829689 PMCID: PMC9952673 DOI: 10.3390/bioengineering10020195] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/21/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
The prevalence of osteoarthritis (OA), a degenerative disorder of joints, has substantially increased in recent years. Its key pathogenic hallmarks include articular cartilage destruction, synovium inflammation, and bone remodeling. However, treatment outcomes are unsatisfactory. Until recently, common therapy methods, such as analgesic and anti-inflammatory treatments, were aimed to treat symptoms that cannot be radically cured. Mesenchymal stem cells (MSCs), i.e., mesoderm non-hematopoietic cells separated from bone marrow, adipose tissue, umbilical cord blood, etc., have been intensively explored as an emerging technique for the treatment of OA over the last few decades. According to existing research, MSCs may limit cartilage degradation in OA by interfering with cellular immunity and secreting a number of active chemicals. This study aimed to examine the potential mechanism of MSCs in the treatment of OA and conduct a thorough review of both preclinical and clinical data.
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Affiliation(s)
- Zehui Lv
- Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Xuejie Cai
- Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Yixin Bian
- Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Zhanqi Wei
- Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Wei Zhu
- Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Xiuli Zhao
- Department of Medical Genetics, Institute of Basic Medical Sciences, School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
- Correspondence: (X.Z.); (X.W.)
| | - Xisheng Weng
- Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Department of State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Correspondence: (X.Z.); (X.W.)
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Day MA, Hancock KJ, Selley RS, Olsen R, Ranawat AS, Nwachukwu BU, Kelly BT, Nawabi DH. Hip Arthroscopy With Bone Marrow Aspirate Injection for Patients With Symptomatic Labral Tears and Early Degenerative Changes Shows Similar Improvement Compared With Patients Undergoing Hip Arthroscopy With Symptomatic Labral Tears Without Arthritis. Arthroscopy 2022; 39:1429-1437. [PMID: 36574821 DOI: 10.1016/j.arthro.2022.12.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/25/2022]
Abstract
PURPOSE To define the clinical effect of intra-articular injection of iliac crest-derived bone marrow aspirate concentrate (BMAC) at the time of hip arthroscopy in patients with symptomatic labral tears and early radiographic degenerative changes. METHODS A retrospective review of a prospectively collected hip registry database was performed. Patients with symptomatic labral tears and Tönnis grade 1 or 2 degenerative changes who underwent labrum-preserving hip arthroscopy with BMAC injection were included and were matched with patients who underwent hip arthroscopy without BMAC injection. Patient-reported outcomes (PROs) collected preoperatively and up to 2 years postoperatively included the modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport, and International Hip Outcome Tool 33 score. Clinical relevance was measured with the minimal clinically important difference, patient acceptable symptom state, and substantial clinical benefit for each outcome score. RESULTS A total of 35 patients underwent labrum-preserving hip arthroscopy with BMAC injection and were matched with 35 control patients. There were no differences in demographic characteristics between the groups (P > .05). The BMAC group consisted of 22 patients (62.9%) with Tönnis grade 1 changes and 13 (37.1%) with Tönnis grade 2 changes, whereas all 35 control patients had Tönnis grade 0 hips. All PROs were significantly improved in both groups at 2 years, with no difference in improvement. The rate of failure requiring conversion to total hip arthroplasty was 14.3% (mean, 1.6 years postoperatively) in the BMAC group and 5.7% (mean, 7 years postoperatively) in the control group (P = .09). The difference in the frequency of patients achieving the minimal clinically important difference, patient acceptable symptom state, and substantial clinical benefit was not statistically significant between cohorts. CONCLUSIONS In a challenging group of patients with symptomatic labral tears and early radiographic degenerative changes, hip arthroscopy with BMAC injection results in statistically and clinically significant improvement in PROs comparable to a group of patients with nonarthritic hips undergoing hip arthroscopy at short-term follow-up. LEVEL OF EVIDENCE Level III, retrospective comparative therapeutic trial.
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Affiliation(s)
- Molly A Day
- Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin, U.S.A.; Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A..
| | - Kyle J Hancock
- Department of Sports Medicine, Desert Orthopaedic Center, Las Vegas, Nevada, U.S.A.; Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
| | - Ryan S Selley
- Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
| | - Reena Olsen
- Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
| | - Anil S Ranawat
- Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
| | - Benedict U Nwachukwu
- Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
| | - Bryan T Kelly
- Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
| | - Danyal H Nawabi
- Sports Medicine Institute, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A
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Strecanska M, Danisovic L, Ziaran S, Cehakova M. The Role of Extracellular Matrix and Hydrogels in Mesenchymal Stem Cell Chondrogenesis and Cartilage Regeneration. LIFE (BASEL, SWITZERLAND) 2022; 12:life12122066. [PMID: 36556431 PMCID: PMC9784885 DOI: 10.3390/life12122066] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/02/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022]
Abstract
Diseases associated with articular cartilage disintegration or loss are still therapeutically challenging. The traditional treatment approaches only alleviate the symptoms while potentially causing serious side effects. The limited self-renewal potential of articular cartilage provides opportunities for advanced therapies involving mesenchymal stem cells (MSCs) that are characterized by a remarkable regenerative capacity. The chondrogenic potential of MSCs is known to be regulated by the local environment, including soluble factors and the less discussed extracellular matrix (ECM) components. This review summarizes the process of chondrogenesis, and also the biological properties of the ECM mediated by mechanotransduction as well as canonical and non-canonical signaling. Our focus is also on the influence of the ECM's physical parameters, molecular composition, and chondrogenic factor affinity on the adhesion, survival, and chondrogenic differentiation of MSCs. These basic biological insights are crucial for a more precise fabrication of ECM-mimicking hydrogels to improve cartilage tissue reconstruction. Lastly, we provide an overview of hydrogel classification and characterization. We also include the results from preclinical models combining MSCs with hydrogels for the treatment of cartilage defects, to support clinical application of this construct. Overall, it is believed that the proper combination of MSCs, hydrogels, and chondrogenic factors can lead to complex cartilage regeneration.
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Affiliation(s)
- Magdalena Strecanska
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Institute of Medical Biology, Genetics, and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Lubos Danisovic
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Institute of Medical Biology, Genetics, and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Stanislav Ziaran
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Department of Urology, Faculty of Medicine, Comenius University, Limbova 5, 833 05 Bratislava, Slovakia
| | - Michaela Cehakova
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Institute of Medical Biology, Genetics, and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
- Correspondence: ; Tel.: +421-2-5935-7215
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Grottkau BE, Hui Z, Pang Y. Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks. Cells 2022; 11:cells11203244. [PMID: 36291114 PMCID: PMC9600996 DOI: 10.3390/cells11203244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 09/28/2022] [Accepted: 10/09/2022] [Indexed: 11/24/2022] Open
Abstract
Articular cartilage lesions are prevalent and affect one out of seven American adults and many young patients. Cartilage is not capable of regeneration on its own. Existing therapeutic approaches for articular cartilage lesions have limitations. Cartilage tissue engineering is a promising approach for regenerating articular neocartilage. Bioassembly is an emerging technology that uses microtissues or micro-precursor tissues as building blocks to construct a macro-tissue. We summarize and highlight the application of bioassembly technology in regenerating articular cartilage. We discuss the advantages of bioassembly and present two types of building blocks: multiple cellular scaffold-free spheroids and cell-laden polymer or hydrogel microspheres. We present techniques for generating building blocks and bioassembly methods, including bioprinting and non-bioprinting techniques. Using a data set of 5069 articles from the last 28 years of literature, we analyzed seven categories of related research, and the year trends are presented. The limitations and future directions of this technology are also discussed.
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10
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Autologous Stem Cells for the Treatment of Chondral Injury and Disease. OPER TECHN SPORT MED 2022. [DOI: 10.1016/j.otsm.2022.150963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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11
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Lee GW, Kwak WK, Lee KB. Effects and Safety of Intra-Articular Sodium Hyaluronate Injection for the Treatment of Ankle Osteoarthritis: A Prospective Clinical Trial. J Foot Ankle Surg 2022; 61:345-349. [PMID: 34801379 DOI: 10.1053/j.jfas.2021.09.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 03/11/2021] [Accepted: 09/08/2021] [Indexed: 02/03/2023]
Abstract
Various nonoperative treatments have been implemented to reduce pain and improve the quality of life in patients with ankle osteoarthritis. Among these treatments, intra-articular hyaluronate injection has proven efficacy and safety in patients with knee osteoarthritis. The purpose of this study was to evaluate the efficacy and complications of hyaluronate injection using various clinical scoring systems. This study included 37 patients with unilateral ankle osteoarthritis (grade 2 or 3 according to the Takakura classification) who did not respond to previous pharmacological treatment. 3 weekly hyaluronate injections (2 mL Hyruan Plus®) were administered. The efficacy of intra-articular hyaluronate injection was evaluated on the basis of patient-reported foot and ankle clinical assessment at a mean follow-up of 13.8 ± 8.3 (range 6-33) months. Ankle Osteoarthritis Scale scores for pain and disability, American Orthopedic Foot and Ankle Society ankle-hindfoot scores, and visual analog scale for pain significantly improved at the final follow-up compared to that before intra-articular hyaluronate injection (p ≤ .05). When patients were dichotomized according to age, sex, body mass index, symptom duration, and Takakura classification, all these factors were not related to clinical outcomes. This study suggests that 3 weekly intra-articular hyaluronate injections can be performed safely to reduce pain and improve function without serious complications in patients with early or intermediate-grade ankle osteoarthritis when patients inadequately respond to medication. Larger controlled studies are needed to clarify the effects of hyaluronate injection and identify patients who can benefit most from hyaluronate injection.
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Affiliation(s)
- Gun-Woo Lee
- Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea
| | - Woo Kyoung Kwak
- Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea
| | - Keun-Bae Lee
- Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
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12
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Martin SD, Kucharik MP, Abraham PF, Nazal MR, Meek WM, Varady NH. Functional Outcomes of Arthroscopic Acetabular Labral Repair with and without Bone Marrow Aspirate Concentrate. J Bone Joint Surg Am 2022; 104:4-14. [PMID: 34648479 DOI: 10.2106/jbjs.20.01740] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Osteoarthritis (OA) of the hip is a debilitating condition associated with inferior outcomes in patients undergoing hip arthroscopy. To provide symptom relief and improve outcomes in these patients, bone marrow aspirate concentrate (BMAC) has been applied as an adjuvant therapy with the hope of halting progression of cartilage damage. The current study examined the clinical efficacy of BMAC application in patients undergoing arthroscopic acetabular labral repair by comparing patient-reported outcome measures (PROMs) between groups with and without BMAC application. METHODS Patients who received BMAC during arthroscopic acetabular labral repair from December 2016 to June 2019 were compared with a control cohort that underwent the same procedure but did not receive BMAC from November 2013 to November 2016. Patients in both cohorts were asked to prospectively complete PROMs prior to surgery and at 3, 6, 12, and 24-month follow-up intervals; those who completed the PROMs at enrollment and the 12-month follow-up were included in the study. An a priori subgroup analysis was performed among patients with moderate cartilage damage (Outerbridge grade 2 or 3). The analyses were adjusted for any differences in baseline factors between groups. RESULTS Sixty-two patients with BMAC application were compared with 62 control patients without BMAC application. When compared with the no-BMAC cohort, the BMAC cohort did not report significantly different mean International Hip Outcome Tool-33 (iHOT-33) scores at any postoperative time point. However, when patients with moderate cartilage damage were compared across groups, the BMAC cohort reported significantly greater mean (95% confidence interval) scores than the no-BMAC cohort at the 12-month (78.6 [72.4 to 84.8] versus 69.2 [63.3 to 75.2]; p = 0.035) and 24-month (82.5 [73.4 to 91.6] versus 69.5 [62.1 to 76.8]; p = 0.030) follow-up. Similarly, these patients reported greater score improvements at 12 months (37.3 [30.3 to 44.3] versus 25.4 [18.7 to 32.0]; p = 0.017) and 24 months (39.6 [30.4 to 48.7] versus 26.4 [19.1 to 33.8]; p = 0.029). CONCLUSIONS Patients with moderate cartilage injury undergoing arthroscopic acetabular labral repair with BMAC application reported significantly greater functional improvements when compared with similar patients without BMAC application. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Scott D Martin
- Sports Medicine, Department of Orthopedic Surgery, Massachusetts General Hospital, Mass General Brigham Integrated Health Care System, Boston, Massachusetts
| | - Michael P Kucharik
- Sports Medicine, Department of Orthopedic Surgery, Massachusetts General Hospital, Mass General Brigham Integrated Health Care System, Boston, Massachusetts
| | - Paul F Abraham
- Department of Orthopaedic Surgery, University of Southern California, Los Angeles, California
| | - Mark R Nazal
- Department of Orthopedic Surgery, University of Kentucky, Lexington, Kentucky
| | - Wendy M Meek
- Sports Medicine, Department of Orthopedic Surgery, Massachusetts General Hospital, Mass General Brigham Integrated Health Care System, Boston, Massachusetts
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13
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Nery C, Prado MP. Diagnosis and Treatment of Talus Osteochondral Lesions: Current Concepts. FOOT AND ANKLE DISORDERS 2022:1065-1105. [DOI: 10.1007/978-3-030-95738-4_48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Menarim BC, El-Sheikh Ali H, Loux SC, Scoggin KE, Kalbfleisch TS, MacLeod JN, Dahlgren LA. Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis. Front Immunol 2021; 12:734322. [PMID: 34956173 PMCID: PMC8692379 DOI: 10.3389/fimmu.2021.734322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 11/09/2021] [Indexed: 01/15/2023] Open
Abstract
Osteoarthritis (OA) may result from impaired ability of synovial macrophages to resolve joint inflammation. Increasing macrophage counts in inflamed joints through injection with bone marrow mononuclear cells (BMNC) induces lasting resolution of synovial inflammation. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of co-expressed gene networks associated with traits from related in vivo and in vitro studies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogen-related gene network. This response was associated with sustained increased expression of two gene networks comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). These networks were common to SF and ISF, but more highly expressed in ISF. Most highly activated pathways in ISF included the mevalonate pathway and PPAR-γ signaling, with pro-resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Lower expression of mevalonate kinase and phospho-PPARγ in synovium from inflamed joints treated with BMNC, and equivalent IL-1β staining between BMNC- and DPBS-treated joints, associates with accomplished resolution in BMNC-treated joints and emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following inflammatory stimulus. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR-γ signaling enhancement for the treatment of arthritic conditions.
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Affiliation(s)
- Bruno C Menarim
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.,Gluck Equine Research Center, Department of Veterinary Sciences, College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States
| | - Hossam El-Sheikh Ali
- Gluck Equine Research Center, Department of Veterinary Sciences, College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States.,Theriogenology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Shavahn C Loux
- Gluck Equine Research Center, Department of Veterinary Sciences, College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States
| | - Kirsten E Scoggin
- Gluck Equine Research Center, Department of Veterinary Sciences, College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States
| | - Theodore S Kalbfleisch
- Gluck Equine Research Center, Department of Veterinary Sciences, College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States
| | - James N MacLeod
- Gluck Equine Research Center, Department of Veterinary Sciences, College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States
| | - Linda A Dahlgren
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
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Combinations of Hydrogels and Mesenchymal Stromal Cells (MSCs) for Cartilage Tissue Engineering-A Review of the Literature. Gels 2021; 7:gels7040217. [PMID: 34842678 PMCID: PMC8628761 DOI: 10.3390/gels7040217] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/11/2021] [Accepted: 11/13/2021] [Indexed: 01/17/2023] Open
Abstract
Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.
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16
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Anz AW, Torres J, Plummer HA, Siew-Yoke Jee C, Dekker TJ, Johnson KB, Saw KY. Mobilized Peripheral Blood Stem Cells are Pluripotent and Can Be Safely Harvested and Stored for Cartilage Repair. Arthroscopy 2021; 37:3347-3356. [PMID: 33940122 DOI: 10.1016/j.arthro.2021.04.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 04/06/2021] [Accepted: 04/15/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The primary objective of this study was to reproduce and validate the harvest, processing and storage of peripheral blood stem cells for a subsequent cartilage repair trial, evaluating safety, reliability, and potential to produce viable, sterile stem cells. METHODS Ten healthy subjects (aged 19-44 years) received 3 consecutive daily doses of filgrastim followed by an apheresis harvest of mononuclear cells on a fourth day. In a clean room, the apheresis product was prepared for cryopreservation and processed into 4 mL aliquots. Sterility and qualification testing were performed pre-processing and post-processing at multiple time points out to 2 years. Eight samples were shipped internationally to validate cell transport potential. One sample from all participants was cultured to test proliferative potential with colony forming unit (CFU) assay. Five samples, from 5 participants were tested for differentiation potential, including chondrogenic, adipogenic, osteogenic, endoderm, and ectoderm assays. RESULTS Fresh aliquots contained an average of 532.9 ± 166. × 106 total viable cells/4 mL vial and 2.1 ± 1.0 × 106 CD34+ cells/4 mL vial. After processing for cryopreservation, the average cell count decreased to 331.3 ± 79. × 106 total viable cells /4 mL vial and 1.5 ± 0.7 × 106 CD34+ cells/4 mL vial CD34+ cells. Preprocessing viability averaged 99% and postprocessing 88%. Viability remained constant after cryopreservation at all subsequent time points. All sterility testing was negative. All samples showed proliferative potential, with average CFU count 301.4 ± 63.9. All samples were pluripotent. CONCLUSIONS Peripheral blood stem cells are pluripotent and can be safely harvested/stored with filgrastim, apheresis, clean-room processing, and cryopreservation. These cells can be stored for 2 years and shipped without loss of viability. CLINICAL RELEVANCE This method represents an accessible stem cell therapy in development to augment cartilage repair.
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Affiliation(s)
- Adam W Anz
- Andrews Institute for Orthopedics & Sports Medicine, Gulf Breeze; Andrews Research & Education Foundation, Gulf Breeze.
| | - Johnny Torres
- Andrews Research & Education Foundation, Gulf Breeze
| | | | | | | | | | - Khay-Yong Saw
- Kuala Lumpur Sports Medicine Centre, Kuala Lumpur, Malaysia
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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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18
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Arthroscopic Subchondral Drilling Followed by Injection of Peripheral Blood Stem Cells and Hyaluronic Acid Showed Improved Outcome Compared to Hyaluronic Acid and Physiotherapy for Massive Knee Chondral Defects: A Randomized Controlled Trial. Arthroscopy 2021; 37:2502-2517. [PMID: 34265388 DOI: 10.1016/j.arthro.2021.01.067] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 01/18/2021] [Accepted: 01/25/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study was to evaluate the safety and efficacy of intra-articular injections of autologous peripheral blood stem cells (PBSCs) plus hyaluronic acid (HA) after arthroscopic subchondral drilling into massive chondral defects of the knee joint and to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than HA plus physiotherapy. METHODS This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores. RESULTS At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures. CONCLUSIONS Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy. LEVEL OF EVIDENCE Level I, RCT.
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Chahla J, Gursoy S. Editorial Commentary: Peripheral Blood Stem Cells Mobilization Using Granulocyte Colony-Stimulating Factor for Articular Cartilage Injuries: Wake Them Up and Make Them Come to You! Arthroscopy 2021; 37:2518-2520. [PMID: 33745936 DOI: 10.1016/j.arthro.2021.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 02/02/2023]
Abstract
Articular cartilage injuries constitute a prevalent musculoskeletal problem in the general population. Restorative cartilage procedures are specifically challenging, as recapitulating hyaline cartilage can be difficult, thus compromising clinical outcomes. Progenitor cells for the treatment of articular cartilage injuries constitute a promising therapeutic method that has been increasing exponentially. Progenitor cells can be obtained from many different human tissues, such as bone marrow, adipose tissue, and muscle, as well as from peripheral blood after mobilizing stem cells from bone marrow with granulocyte colony-stimulating factor simulation. The minimally invasiveness, low complication rate, and efficacy of peripheral blood stem cells has gained significant attention and rapidly has become a promising source of progenitor cell delivery in the past decade.
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20
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Menarim BC, MacLeod JN, Dahlgren LA. Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair. World J Stem Cells 2021; 13:825-840. [PMID: 34367479 PMCID: PMC8316866 DOI: 10.4252/wjsc.v13.i7.825] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/03/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Osteoarthritis (OA) is the most prevalent joint disease causing major disability and medical expenditures. Synovitis is a central feature of OA and is primarily driven by macrophages. Synovial macrophages not only drive inflammation but also its resolution, through a coordinated, simultaneous expression of pro- and anti-inflammatory mechanisms that are essential to counteract damage and recover homeostasis. Current OA therapies are largely based on anti-inflammatory principles and therefore block pro-inflammatory mechanisms such as prostaglandin E2 and Nuclear factor-kappa B signaling pathways. However, such mechanisms are also innately required for mounting a pro-resolving response, and their blockage often results in chronic low-grade inflammation. Following minor injury, macrophages shield the damaged area and drive tissue repair. If the damage is more extensive, macrophages incite inflammation recruiting more macrophages from the bone marrow to maximize tissue repair and ultimately resolve inflammation. However, sustained damage and inflammation often overwhelms pro-resolving mechanisms of synovial macrophages leading to the chronic inflammation and related tissue degeneration observed in OA. Recently, experimental and clinical studies have shown that joint injection with autologous bone marrow mononuclear cells replenishes inflamed joints with macrophage and hematopoietic progenitors, enhancing mechanisms of inflammation resolution, providing remarkable and long-lasting effects. Besides creating an ideal environment for resolution with high concentrations of interleukin-10 and anabolic growth factors, macrophage progenitors also have a direct role in tissue repair. Macrophages constitute a large part of the early granulation tissue, and further transdifferentiate from myeloid into a mesenchymal phenotype. These cells, characterized as fibrocytes, are essential for repairing osteochondral defects. Ongoing “omics” studies focused on identifying key drivers of macrophage-mediated resolution of joint inflammation and those required for efficient osteochondral repair, have the potential to uncover ways for developing engineered macrophages or off-the-shelf pro-resolving therapies that can benefit patients suffering from many types of arthropaties, not only OA.
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Affiliation(s)
- Bruno C Menarim
- Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546, United States
| | - James N MacLeod
- Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546, United States
| | - Linda A Dahlgren
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, United States
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21
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Rhatomy S, Dilogo IH. Core Decompression and Biological Treatment in Osteonecrosis of the Hip due to Systemic Lupus Erythematosus, 8-year Follow-up: A Case Report. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.5798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Osteonecrosis most commonly affects the femoral head, especially in middle-aged adults. It can be caused by trauma, chronic inflammation, or infection. It leads to collapse of the entire femoral head and culminates with total hip replacement.
CASE REPORT: A 29-year-old female with systemic lupus erythematosus (SLE) had a chief complaint of bilateral hip pain. She was diagnosed with early osteonecrosis of the femoral head (FICAT stage II) using magnetic resonance imaging and core decompression surgery was performed using three small diameter (4 mm) drillings and added biological treatment. She was evaluated with a visual analog scale (VAS), Harris hip score (HHS), and plain radiography in the pre-operative stage and post-operative follow-up.
RESULTS: Functional outcome at 8-year follow-up showed improvement with significantly decreased VAS (pre-operative: 5, post-operative: 0), significant improvement of HHS from 52.725 points (poor) pre-operative to 92.025 points (excellent) post-operative, and subsided femoral head lesion.
CONCLUSIONS: Surgical decompression and biological treatment result in decreased intraosseous pressure and enhanced osteogenesis. It can restrict the SLE disease progression and limit the number of cell death.
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22
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Dekker TJ, Aman ZS, DePhillipo NN, Dickens JF, Anz AW, LaPrade RF. Chondral Lesions of the Knee: An Evidence-Based Approach. J Bone Joint Surg Am 2021; 103:629-645. [PMID: 33470591 DOI: 10.2106/jbjs.20.01161] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
➤ Management of chondral lesions of the knee is challenging and requires assessment of several factors including the size and location of the lesion, limb alignment and rotation, and the physical and mental health of the individual patient. ➤ There are a multitude of options to address chondral pathologies of the knee that allow individualized treatment for the specific needs and demands of the patient. ➤ Osteochondral autograft transfer remains a durable and predictable graft option in smaller lesions (<2 cm2) in the young and active patient population. ➤ Both mid-term and long-term results for large chondral lesions (≥3 cm2) of the knee have demonstrated favorable results with the use of osteochondral allograft or matrix-associated chondrocyte implantation. ➤ Treatment options for small lesions (<2 cm2) include osteochondral autograft transfer and marrow stimulation and/or microfracture with biologic adjunct, while larger lesions (≥2 cm2) are typically treated with osteochondral allograft transplantation, particulated juvenile articular cartilage, or matrix-associated chondrocyte implantation. ➤ Emerging technologies, such as allograft scaffolds and cryopreserved allograft, are being explored for different graft sources to address complex knee chondral pathology; however, further study is needed.
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Affiliation(s)
- Travis J Dekker
- Division of Orthopaedics, Department of Surgery, Eglin Air Force Base, Eglin, Florida
| | - Zachary S Aman
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | | | - Jonathan F Dickens
- Division of Orthopaedics, Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Adam W Anz
- Andrews Research & Education Foundation, Gulf Breeze, Florida
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Lana JF, da Fonseca LF, Azzini G, Santos G, Braga M, Cardoso Junior AM, Murrell WD, Gobbi A, Purita J, Percope de Andrade MA. Bone Marrow Aspirate Matrix: A Convenient Ally in Regenerative Medicine. Int J Mol Sci 2021; 22:ijms22052762. [PMID: 33803231 PMCID: PMC7963152 DOI: 10.3390/ijms22052762] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/17/2021] [Accepted: 02/24/2021] [Indexed: 02/06/2023] Open
Abstract
The rise in musculoskeletal disorders has prompted medical experts to devise novel effective alternatives to treat complicated orthopedic conditions. The ever-expanding field of regenerative medicine has allowed researchers to appreciate the therapeutic value of bone marrow-derived biological products, such as the bone marrow aspirate (BMA) clot, a potent orthobiologic which has often been dismissed and regarded as a technical complication. Numerous in vitro and in vivo studies have contributed to the expansion of medical knowledge, revealing optimistic results concerning the application of autologous bone marrow towards various impactful disorders. The bone marrow accommodates a diverse family of cell populations and a rich secretome; therefore, autologous BMA-derived products such as the “BMA Matrix”, may represent a safe and viable approach, able to reduce the costs and some drawbacks linked to the expansion of bone marrow. BMA provides —it eliminates many hurdles associated with its preparation, especially in regards to regulatory compliance. The BMA Matrix represents a suitable alternative, indicated for the enhancement of tissue repair mechanisms by modulating inflammation and acting as a natural biological scaffold as well as a reservoir of cytokines and growth factors that support cell activity. Although promising, more clinical studies are warranted in order to further clarify the efficacy of this strategy.
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Affiliation(s)
- José Fábio Lana
- IOC—Instituto do Osso e da Cartilagem, 1386 Presidente Kennedy Avenue, Indaiatuba 13334-170, Brazil; (J.F.L.); (G.A.)
| | | | - Gabriel Azzini
- IOC—Instituto do Osso e da Cartilagem, 1386 Presidente Kennedy Avenue, Indaiatuba 13334-170, Brazil; (J.F.L.); (G.A.)
| | - Gabriel Santos
- IOC—Instituto do Osso e da Cartilagem, 1386 Presidente Kennedy Avenue, Indaiatuba 13334-170, Brazil; (J.F.L.); (G.A.)
- Correspondence:
| | - Marcelo Braga
- Hospital São Judas Tadeu, 150 Cel. João Notini St, Divinópolis 35500-017, Brazil;
| | - Alvaro Motta Cardoso Junior
- Núcleo Avançado de Estudos em Ortopedia e Neurocirurgia, 2144 Ibirapuera Avenue, São Paulo 04028-001, Brazil;
| | - William D. Murrell
- Abu Dhabi Knee and Sports Medicine, Healthpoint Hospital, Zayed Sports City, Between Gate 1 and 6, Abu Dhabi 00000 (P. O. Box No. 112308), United Arab Emirates;
- 411th Hospital Center, Bldg 938, Birmingham Ave, Naval Air Station, Jacksonville, FL 32212, USA
| | - Alberto Gobbi
- O.A.S.I. Bioresearch Foundation Gobbi Onlus, 20133 Milano, Italy;
| | - Joseph Purita
- Institute of Regenerative Medicine, Boca Raton, FL 33432, USA;
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DeFroda SF, Cregar W, Vadhera A, Singh H, Perry A, Chahla J. Arthroscopic Autologous Chondrocyte Bone Grafting of a Lateral Tibial Plateau Chondral Defect. Arthrosc Tech 2021; 10:e861-e865. [PMID: 33738225 PMCID: PMC7953324 DOI: 10.1016/j.eats.2020.10.078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 10/30/2020] [Indexed: 02/03/2023] Open
Abstract
Tibial plateau chondral defects can be difficult to diagnose and treat. Although grafting of femoral and patella chondral defects has become relatively commonplace, the tibial plateau offers unique challenges for some of the grafting techniques used in these locations, mostly because of limitations with exposure even in an open approach. Arthroscopic surgery makes treatment of these lesions more feasible, as it affords better access and visualization of tibial defects. The purpose of this article is to describe the arthroscopic management of a lateral tibial plateau chondral defect via autologous chondrocyte bone grafting. The technique consists of harvest of autologous cartilage from the intercondylar notch and repair of the tibial plateau defect with a slurry of autologous chondrocytes and bone marrow aspirate concentrate. In addition, CO2 is used as a medium to distend the joint in a tight compartment to keep the chondral defect dry. This technique is technically simple and does not require an extensive open technique or an expensive osteochondral allograft. It also avoids the staged management required in other types of autologous chondrocyte implantation, which require cartilage biopsy to produce a final product for implantation.
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Affiliation(s)
| | | | | | | | | | - Jorge Chahla
- Address correspondence to Jorge Chahla, M.D., Ph.D., Rush University Medical Center, 1611 W Harrison St, Chicago, IL 60612, U.S.A.
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25
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Laurent A, Abdel-Sayed P, Ducrot A, Hirt-Burri N, Scaletta C, Jaccoud S, Nuss K, de Buys Roessingh AS, Raffoul W, Pioletti D, von Rechenberg B, Applegate LA, Darwiche S. Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation. Biomolecules 2021; 11:250. [PMID: 33572428 PMCID: PMC7916236 DOI: 10.3390/biom11020250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/04/2021] [Accepted: 02/04/2021] [Indexed: 12/27/2022] Open
Abstract
Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as preliminary preclinical hECP safety. Optimized cell banking workflows were proposed, potentially generating millions of safe and sustainable therapeutic products. Furthermore, clinical hECP doses were characterized as non-toxic in a standardized chorioallantoic membrane model. Lastly, a MACI-like protocol, including hECPs, was applied in a three-month GLP pilot safety evaluation in a caprine model of full-thickness articular cartilage defect. The safety of hECP transplantation was highlighted in xenogeneic settings, along with confirmed needs for optimal cell delivery vehicles and implantation techniques favoring effective cartilage repair or regeneration.
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Affiliation(s)
- Alexis Laurent
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
- Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland
| | - Philippe Abdel-Sayed
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
| | - Aurélie Ducrot
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
| | - Nathalie Hirt-Burri
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
| | - Corinne Scaletta
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
| | - Sandra Jaccoud
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
- Laboratory of Biomechanical Orthopedics, Ecole Polytechnique Fédérale de Lausanne, CH-2002 Neuchâtel, Switzerland;
| | - Katja Nuss
- Musculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, Switzerland; (K.N.); (B.v.R.)
| | - Anthony S. de Buys Roessingh
- Children and Adolescent Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland;
| | - Wassim Raffoul
- Plastic, Reconstructive, and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland;
| | - Dominique Pioletti
- Laboratory of Biomechanical Orthopedics, Ecole Polytechnique Fédérale de Lausanne, CH-2002 Neuchâtel, Switzerland;
| | - Brigitte von Rechenberg
- Musculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, Switzerland; (K.N.); (B.v.R.)
- Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland
| | - Lee Ann Applegate
- Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, Switzerland; (A.L.); (P.A.-S.); (A.D.); (N.H.-B.); (C.S.); (S.J.); (L.A.A.)
- Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland
- Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215123, Jiangsu, China
| | - Salim Darwiche
- Musculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, Switzerland; (K.N.); (B.v.R.)
- Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland
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Deng Z, Jin J, Wang S, Qi F, Chen X, Liu C, Li Y, Ma Y, Lyu F, Zheng Q. Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering. ANNALS OF TRANSLATIONAL MEDICINE 2021; 8:1598. [PMID: 33437797 PMCID: PMC7791208 DOI: 10.21037/atm-20-2342] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Stem cell-based therapy is a promising treatment for cartilage defects due to the pluripotency, abundant sources and low immunogenicity of stem cells. Hydrogels are a promising class of biomaterials for cartilage engineering and are characterized by bioactivity, degradability and elasticity as well as provide water content and mechanical support. The combination of stem cells and hydrogels opens new possibilities for cartilage tissue engineering. However, the selection of suitable types of stem cells and hydrogels is difficult. Currently, various types of stem cells, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and peripheral blood mononuclear cells (PBMSCs), and various types of hydrogels, including natural polymers, chemically modified natural polymers and synthetic polymers, have been explored based on their potential for cartilage tissue engineering. These materials are used independently or in combination; however, there is no clear understanding of their merits and disadvantages with regard to their suitability for cartilage repair. In this article, we aim to review recent progress in the use of stem cell-hydrogel hybrid constructs for cartilage tissue engineering. We focus on the effects of stem cell types and hydrogel types on efficient chondrogenesis from cellular, preclinical and clinical perspectives. We compare and analyze the advantages and disadvantages of these cells and hydrogels with the hope of increasing discussion of their suitability for cartilage repair and present our perspective on their use for the improvement of physical and biological properties for cartilage tissue engineering.
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Affiliation(s)
- Zhantao Deng
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jiewen Jin
- Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shuai Wang
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Fangjie Qi
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xuepan Chen
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Chang Liu
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yanbing Li
- Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yuanchen Ma
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Fengjuan Lyu
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.,South China University of Technology-the University of Western Australia Joint Center for Regenerative Medicine Research, School of Medicine, South China University of Technology, Guangzhou, China
| | - Qiujian Zheng
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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27
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Shimozono Y, Fansa AM, Kennedy JG. Ankle Joint Cartilage Pathology and Repair. LOWER EXTREMITY JOINT PRESERVATION 2021:329-339. [DOI: 10.1007/978-3-030-57382-9_30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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28
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Liu YYF, Lu Y, Oh S, Conduit GJ. Machine learning to predict mesenchymal stem cell efficacy for cartilage repair. PLoS Comput Biol 2020; 16:e1008275. [PMID: 33027251 PMCID: PMC7571701 DOI: 10.1371/journal.pcbi.1008275] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 10/19/2020] [Accepted: 08/20/2020] [Indexed: 12/13/2022] Open
Abstract
Inconsistent therapeutic efficacy of mesenchymal stem cells (MSCs) in regenerative medicine has been documented in many clinical trials. Precise prediction on the therapeutic outcome of a MSC therapy based on the patient's conditions would provide valuable references for clinicians to decide the treatment strategies. In this article, we performed a meta-analysis on MSC therapies for cartilage repair using machine learning. A small database was generated from published in vivo and clinical studies. The unique features of our neural network model in handling missing data and calculating prediction uncertainty enabled precise prediction of post-treatment cartilage repair scores with coefficient of determination of 0.637 ± 0.005. From this model, we identified defect area percentage, defect depth percentage, implantation cell number, body weight, tissue source, and the type of cartilage damage as critical properties that significant impact cartilage repair. A dosage of 17 - 25 million MSCs was found to achieve optimal cartilage repair. Further, critical thresholds at 6% and 64% of cartilage damage in area, and 22% and 56% in depth were predicted to significantly compromise on the efficacy of MSC therapy. This study, for the first time, demonstrated machine learning of patient-specific cartilage repair post MSC therapy. This approach can be applied to identify and investigate more critical properties involved in MSC-induced cartilage repair, and adapted for other clinical indications.
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Affiliation(s)
- Yu Yang Fredrik Liu
- Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom
- * E-mail:
| | - Yin Lu
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
| | - Steve Oh
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
| | - Gareth J. Conduit
- Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom
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29
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Kim GB, Kim JD, Choi Y, Choi CH, Lee GW. Intra-Articular Bone Marrow Aspirate Concentrate Injection in Patients with Knee Osteoarthritis. APPLIED SCIENCES 2020; 10:5945. [DOI: 10.3390/app10175945] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/04/2024]
Abstract
We aimed to evaluate the 5-year follow-up outcomes of an intra-articular bone marrow aspirate concentrate (BMAC) injection in patients with knee osteoarthritis. This is the first study to report the outcomes following BMAC injections over a 5-year follow-up period. Seventy knees of 37 patients, including 33 bilateral knees, were investigated. The primary outcome was the visual analogue scale (VAS) score for pain in the knee joint, and the secondary outcomes were the International Knee Documentation Committee score, the 36-Item Short Form Health Survey score, the Knee injury Osteoarthritis Outcome Score, Lysholm Knee Questionnaire/Tegner activity scale, BMAC injection-induced complications, and 5-year treatment success rate. The 5-year post-injection VAS scores (4.7 ± 0.5) were significantly lower than the preoperative scores (8.3 ± 1.2) (p = 0.01). Improvement in VAS scores was significantly greater in patients with Kellgren–Lawrence (K-L) Grade I or II than those in those with K-L Grade III or IV. Improvement in other clinical parameters and success rates were significantly low and the rates of secondary operation and failure were significantly higher in patients with K-L Grades III or IV. Intra-articular BMAC injections could be useful for managing patients with K-L Grades I or II osteoarthritis.
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Affiliation(s)
- Gi Beom Kim
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea
| | - Jae-Do Kim
- Department of Orthopedic Surgery, Kosin University College of Medicine, Kosin University Gospel Hospital, 34 Amnam-dong, Seogu, Busan 602-702, Korea
| | - Young Choi
- Department of Orthopedic Surgery, Kosin University College of Medicine, Kosin University Gospel Hospital, 34 Amnam-dong, Seogu, Busan 602-702, Korea
| | - Chang Hyun Choi
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea
| | - Gun Woo Lee
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea
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30
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Freitag J, Shah K, Wickham J, Li D, Norsworthy C, Tenen A. Evaluation of autologous adipose-derived mesenchymal stem cell therapy in focal chondral defects of the knee: a pilot case series. Regen Med 2020; 15:1703-1717. [PMID: 32735154 DOI: 10.2217/rme-2020-0027] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Aim: To evaluate the safety, pain, functional and structural improvements after autologous adipose-derived mesenchymal stem cell (ADMSC) therapy in combination with arthroscopic abrasion arthroplasty in focal chondral defects of the knee. Methods: Eight patients with a focal full thickness chondral defect of the knee underwent arthroscopic abrasion arthroplasty followed by postoperative intra-articular injections of autologous ADMSCs (50 × 106 ADMSCs at baseline and 6 months). Clinical outcome was assessed using numeric pain rating scale, Knee Injury and Osteoarthritis Outcome Score and the Western Ontario and McMaster Universities Osteoarthritis Index. Structural outcome was determined by magnetic resonance imaging. Outcome was assessed over 24 months. Results: No serious adverse events occurred. Participants observed clinically significant improvement in pain and function. Magnetic resonance imaging analysis showed cartilage regeneration with T2 mapping values comparable to hyaline cartilage. Conclusion: Arthroscopic abrasion arthroplasty in combination with intra-articular ADMSC therapy results in reproducible pain, functional and structural improvements with regeneration of hyaline-like cartilage. Trial registration number: ACTRN12617000638336.
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Affiliation(s)
- Julien Freitag
- Charles Sturt University, Orange, NSW, Australia.,Magellan Stem Cells, Box Hill, Victoria, Australia.,Melbourne Stem Cell Centre, Box Hill, Victoria, Australia
| | - Kiran Shah
- Magellan Stem Cells, Box Hill, Victoria, Australia.,Swinburne University, Melbourne, Victoria, Australia
| | | | - Douglas Li
- Orthopaedics Sports Arthroplasty, Melbourne, Victoria, Australia
| | | | - Abi Tenen
- Magellan Stem Cells, Box Hill, Victoria, Australia.,Melbourne Stem Cell Centre, Box Hill, Victoria, Australia.,Monash University, Monash, Victoria, Australia
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Freitag J, Wickham J, Shah K, Tenen A. Effect of autologous adipose-derived mesenchymal stem cell therapy in the treatment of an osteochondral lesion of the ankle. BMJ Case Rep 2020; 13:13/7/e234595. [PMID: 32641315 PMCID: PMC7348644 DOI: 10.1136/bcr-2020-234595] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Osteochondral lesions (OCLs) of the talus are rare but can be associated with significant morbidity and may lead to the development of osteoarthritis. An improved understanding of the action of mesenchymal stem cells (MSCs) has seen renewed interest in their role in cartilage repair, with early preclinical and clinical research showing benefits in symptomatic and structural improvement. A 42-year-old man presented with an unstable OCL of the talus and onset of early osteoarthritis with a history of multiple previous ankle arthroscopies for ankle impingement. The patient underwent arthroscopic removal of the OCL in combination with adipose-derived MSC therapy. The patient reported progressive improvement as measured by the validated Foot and Ankle Disability Index. Repeat MRI with additional T2 mapping techniques showed successful regeneration of hyaline-like cartilage. This case is the first to show the successful use of MSC therapy in the management of an ankle OCL. Trial registration: Australian New Zealand Clinical Trials Registry - ACTRN12617000638336.
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Affiliation(s)
- Julien Freitag
- Melbourne Stem Cell Centre, Box Hill North, Victoria, Australia .,School of Biomedical Sciences, Charles Sturt University - Orange Campus, Orange, New South Wales, Australia.,Magellan Stem Cells, Box Hill North, Victoria, Australia
| | - James Wickham
- School of Biomedical Sciences, Charles Sturt University - Orange Campus, Orange, New South Wales, Australia
| | - Kiran Shah
- Magellan Stem Cells, Box Hill North, Victoria, Australia.,Swinburne University of Technology, Melbourne, Victoria, Australia
| | - Abi Tenen
- Melbourne Stem Cell Centre, Box Hill North, Victoria, Australia.,Magellan Stem Cells, Box Hill North, Victoria, Australia.,School of Primary Health Care, Monash University, Notting Hill, Victoria, Australia
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Gianakos AL, Haring RS, Shimozono Y, Fragomen A, Kennedy JG. Effect of Microfracture on Functional Outcomes and Subchondral Sclerosis Following Distraction Arthroplasty of the Ankle Joint. Foot Ankle Int 2020; 41:631-638. [PMID: 32354229 DOI: 10.1177/1071100720917144] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Treatment for post-traumatic osteoarthritis (PTOA) of the ankle remains challenging. Distraction arthroplasty (DA) is an alternative for patients who are averse to or poor candidates for arthrodesis or joint replacement. The purpose of this study was to examine the role of microfracture (MFX) and concentrated bone marrow aspirate (CBMA) on the outcome of patients undergoing DA for end-stage PTOA of the ankle joint. METHODS Ninety-five patients who underwent DA for the treatment of end stage PTOA from 2009 to 2014 were selected from the hospital ankle registry. Demographic data, functional activity levels, complications, and radiographs taken at 6, 12, 24, and 36 months postoperatively were reviewed. Foot and Ankle Outcome Scores (FAOS) were obtained at the same time intervals. A total of 78 patients were included in this study. Interventions were divided into 4 groups for comparison: DA+MFX (n = 8), DA+MFX+CBMA (n = 35), DA+CBMA (n = 22), and DA alone (n = 13). RESULTS Patients undergoing DA+MFX or DA+MFX+CBMA had significantly worse motion (P = .003) when compared with DA alone. Patients undergoing MFX had significantly reduced postoperative joint space and a greater length of time to return to activity when compared to subgroups not using MFX (P = .01). The use of MFX was associated with significantly lower FAOS scores. CONCLUSION The current study showed no benefit from MFX when combined with DA in the treatment of PTOA. CBMA may have helped mitigate the adverse effect of MFX but conferred no benefit when used with DA alone. DA remains a useful alternative to ankle arthrodesis and arthroplasty in patients with PTOA. However, MFX and biologic augmentation using CBMA appeared to have no additional benefit. LEVEL OF EVIDENCE Level III, comparative study.
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Affiliation(s)
- Arianna L Gianakos
- Department of Orthopedic Surgery, Robert Wood Johnson Barnabas Health-Jersey City Medical Center, Jersey City, NJ, USA
| | - R Sterling Haring
- Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA.,Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Yoshiharu Shimozono
- Department of Orthopedic Surgery, Teikyo University School of Medicine, Tokyo, Japan.,Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Austin Fragomen
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY, USA
| | - John G Kennedy
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY, USA
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Chen YR, Yan X, Yuan FZ, Ye J, Xu BB, Zhou ZX, Mao ZM, Guan J, Song YF, Sun ZW, Wang XJ, Chen ZY, Wang DY, Fan BS, Yang M, Song ST, Jiang D, Yu JK. The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review. Front Pharmacol 2020; 11:404. [PMID: 32308625 PMCID: PMC7145972 DOI: 10.3389/fphar.2020.00404] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 03/17/2020] [Indexed: 12/13/2022] Open
Abstract
Background Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. Methods PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. Results A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. Conclusion Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.
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Affiliation(s)
- You-Rong Chen
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Xin Yan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Fu-Zhen Yuan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jing Ye
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Bing-Bing Xu
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Zhu-Xing Zhou
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Zi-Mu Mao
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jian Guan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Yi-Fan Song
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Ze-Wen Sun
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.,School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Xin-Jie Wang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Ze-Yi Chen
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Ding-Yu Wang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Bao-Shi Fan
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.,School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Meng Yang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.,School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Shi-Tang Song
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Dong Jiang
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Jia-Kuo Yu
- Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
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Focal Chondral and Subchondral Bone Lesions of the Knee: Current Evidence for the Use of Biologic Treatment. OPER TECHN SPORT MED 2020. [DOI: 10.1016/j.otsm.2019.150716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Anz AW, Hubbard R, Rendos NK, Everts PA, Andrews JR, Hackel JG. Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 1 Year: A Prospective, Randomized Trial. Orthop J Sports Med 2020; 8:2325967119900958. [PMID: 32118081 PMCID: PMC7029538 DOI: 10.1177/2325967119900958] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 10/25/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Approximately 47 million people in the United States have been diagnosed with arthritis. Autologous platelet-rich plasma (PRP) injections have been documented to alleviate symptoms related to knee osteoarthritis (OA) in randomized controlled trials, systematic reviews, and meta-analyses. Autologous bone marrow aspirate concentrate (BMC) injections have also emerged as a treatment option for knee OA, with a limited clinical evidence base. Purpose: To compare the efficacy of BMC to PRP for the treatment of knee OA regarding pain and function at multiple time points up to 12 months after an injection. We hypothesized that BMC will be more effective in improving outcomes in patients with knee OA. Study Design: Randomized controlled trial; Level of evidence, 2 Methods: A total of 90 participants aged between 18 and 80 years with symptomatic knee OA (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaires before and 1, 3, 6, 9, and 12 months after a single intra-articular injection of leukocyte-rich PRP or BMC. Results: There were no statistically significant differences in baseline IKDC or WOMAC scores between the 2 groups. All IKDC and WOMAC scores for both the PRP and BMC groups significantly improved from baseline to 1 month after the injection (P < .001). These improvements were sustained for 12 months after the injection, with no difference between PRP and BMC at any time point. Conclusion: Both PRP and BMC were effective in improving patient-reported outcomes in patients with mild to moderate knee OA for at least 12 months; neither treatment provided a superior clinical benefit. Autologous PRP and BMC showed promising clinical potential as therapeutic agents for the treatment of OA, and while PRP has strong clinical evidence to support its efficacy, BMC has limited support. This study did not prove BMC to be superior to PRP, providing guidance to clinicians treating OA. It is possible that the results were affected by patients knowing that there was no control group. Registration: NCT03289416 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Adam W Anz
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
| | - Ryan Hubbard
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
| | - Nicole K Rendos
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
| | | | - James R Andrews
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
| | - Joshua G Hackel
- Andrews Research & Education Foundation, Gulf Breeze, Florida, USA
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Menarim BC, Gillis KH, Oliver A, Mason C, Werre SR, Luo X, Byron CR, Kalbfleisch TS, MacLeod JN, Dahlgren LA. Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy. FASEB J 2020; 34:4430-4444. [PMID: 32030831 DOI: 10.1096/fj.201902698r] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/13/2020] [Accepted: 01/13/2020] [Indexed: 02/06/2023]
Abstract
Synovial inflammation is a central feature of osteoarthritis (OA), elicited when local regulatory macrophages (M2-like) become overwhelmed, activating an inflammatory response (M1-like). Bone marrow mononuclear cells (BMNC) are a source of naïve macrophages capable of reducing joint inflammation and producing molecules essential for cartilage metabolism. This study investigated the response of BMNC to normal (SF) and inflamed synovial fluid (ISF). Equine BMNC cultured in autologous SF or ISF (n = 8 horses) developed into macrophage-rich cultures with phenotypes similar to cells native to normal SF and became more confluent in ISF (~100%) than SF (~25%). BMNC cultured in SF or ISF were neither M1- nor M2-like, but exhibited aspects of both phenotypes and a regulatory immune response, characterized by increasing counts of IL-10+ macrophages, decreasing IL-1β concentrations and progressively increasing IL-10 and IGF-1 concentrations. Changes were more marked in ISF and suggest that homeostatic mechanisms were preserved over time and were potentially favored by progressive cell proliferation. Collectively, our data suggest that intra-articular BMNC could increase synovial macrophage counts, potentiating the macrophage- and IL-10-associated mechanisms of joint homeostasis lost during the progression of OA, preserving the production of cytokines involved in tissue repair (PGE2 , IL-10) generally impaired by frequently used corticosteroids.
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Affiliation(s)
- Bruno C Menarim
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Kiersten H Gillis
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Andrea Oliver
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Caitlin Mason
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Stephen R Werre
- Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Xin Luo
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Christopher R Byron
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
| | - Theodore S Kalbfleisch
- Maxwell Gluck Equine Research Center, College of Agricultural and Veterinary Sciences, University of Kentucky, Lexington, KY, USA
| | - James N MacLeod
- Maxwell Gluck Equine Research Center, College of Agricultural and Veterinary Sciences, University of Kentucky, Lexington, KY, USA
| | - Linda A Dahlgren
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
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Haverkamp D. An Update on Ankle Arthroscopy: Current Evidence and Practical Recommendations for 2020. ESSKA INSTRUCTIONAL COURSE LECTURE BOOK 2020:127-132. [DOI: 10.1007/978-3-662-61264-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Menarim BC, Gillis KH, Oliver A, Mason C, Ngo Y, Werre SR, Barrett SH, Luo X, Byron CR, Dahlgren LA. Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis. FASEB J 2019; 33:14337-14353. [PMID: 31665925 DOI: 10.1096/fj.201901684rr] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Osteoarthritis (OA) is characterized by macrophage-driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injection. Contralateral joints were injected with saline. Synovial fluid was collected at 24, 96, and 144 h for cytology, cytokine quantification, and flow cytometry. At 144 h, horses were euthanatized, joints were evaluated, and synovium was harvested for histology and immunohistochemistry. Four days after BMNC treatment, inflamed joints had 24% higher macrophage counts with 10% more IL-10+ cells than saline-treated controls. BMNC-treated joints showed gross and analytical improvements in synovial fluid and synovial membrane, with increasing regulatory macrophages and synovial fluid IL-10 concentrations compared with saline-treated controls. BMNC-treated joints were comparable to healthy joints histologically, which remained abnormal in saline-treated controls. Autologous BMNCs are readily available, regulate synovitis through macrophage-associated effects, and can benefit thousands of patients with OA.-Menarim, B. C., Gillis, K. H., Oliver, A., Mason, C., Ngo, Y., Werre, S. R., Barrett, S. H., Luo, X., Byron, C. R., Dahlgren, L. A. Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis.
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Affiliation(s)
- Bruno C Menarim
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
| | - Kiersten H Gillis
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
| | - Andrea Oliver
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
| | - Caitlin Mason
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
| | - Ying Ngo
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
| | - Stephen R Werre
- Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA; and
| | - Sarah H Barrett
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Xin Luo
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Christopher R Byron
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
| | - Linda A Dahlgren
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA
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Shimozono Y, Vannini F, Ferkel RD, Nakamura N, Kennedy JG. Restorative procedures for articular cartilage in the ankle: state-of-the-art review. J ISAKOS 2019. [DOI: 10.1136/jisakos-2017-000163] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Sadlik B, Kolodziej L, Puszkarz M, Laprus H, Mojzesz M, Whyte GP. Surgical repair of osteochondral lesions of the talus using biologic inlay osteochondral reconstruction: Clinical outcomes after treatment using a medial malleolar osteotomy approach compared to an arthroscopically-assisted approach. Foot Ankle Surg 2019; 25:449-456. [PMID: 30321967 DOI: 10.1016/j.fas.2018.02.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 02/13/2018] [Accepted: 02/14/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Surgical treatment of osteochondral lesions of the talus affecting the medial aspect of the talar dome is typically performed using medial malleolar osteotomy to optimize access. This study compares clinical outcomes of lesions repaired using biologic inlay osteochondral reconstruction in patients who did or did not undergo medial malleolar osteotomy, depending on defect dimensions. METHODS Patients treated for osteochonral lesions of the talus through a medial mallolar approach or arthroscopically-assisted approach were prospectively followed. Assessment tools consisted of the visual analogue scale (VAS) and the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot score (AOFAS). The magnetic resonance observation of cartilage repair tissue (MOCART) score was used postoperatively. RESULTS Data for 24 patients (mean age 34years, mean follow-up 22 months) was analyzed. Mean preoperative/final AOFAS and VAS in those who underwent osteotomy were 57.7/81.2 and 5.7/1.9 (p<0.001), respectively. In those who underwent arthroscopically-assisted reconstruction, mean preoperative/final AOFAS and VAS were 54.4/84.0 and 7.6/2.0 (p<0.001), respectively. There was no difference in mean MOCART score (p=0.662) for those treated with osteotomy (67.3) compared to those without (70.8). CONCLUSIONS Osteochondral lesions of the talar dome can be treated successfully by biological inlay osteochondral reconstruction technique without medial malleolar osteotomy, with good to excellent clinical outcomes expected. MRI demonstrates good integration of the graft into surrounding tissue.
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Affiliation(s)
- Boguslaw Sadlik
- Biological Joint Reconstruction Department, St. Luke's Hospital, Bielsko-Biala, Poland
| | - Lukasz Kolodziej
- Orthopaedic, Traumatology, and Orthopaedic Oncology Clinic, Pomeranian Medical University, Szczecin, Poland
| | - Mariusz Puszkarz
- Biological Joint Reconstruction Department, St. Luke's Hospital, Bielsko-Biala, Poland
| | - Hubert Laprus
- Biological Joint Reconstruction Department, St. Luke's Hospital, Bielsko-Biala, Poland
| | - Michal Mojzesz
- Biological Joint Reconstruction Department, St. Luke's Hospital, Bielsko-Biala, Poland
| | - Graeme P Whyte
- Cornell University, Weill Medical College, New York Presbyterian Hospital/Queens, New York, NY, USA.
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Monckeberg JE, Rafols C, Apablaza F, Gerhard P, Rosales J. Intra-articular administration of peripheral blood stem cells with platelet-rich plasma regenerated articular cartilage and improved clinical outcomes for knee chondral lesions. Knee 2019; 26:824-831. [PMID: 31227435 DOI: 10.1016/j.knee.2019.05.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 04/10/2019] [Accepted: 05/14/2019] [Indexed: 02/02/2023]
Abstract
PURPOSE To determine whether intra-articular injections of peripheral blood stem cells improved the regeneration of articular cartilage in patients with osteochondral knee injuries. METHODS This prospective study included 20 patients with grade 3b knee osteochondral lesions who underwent knee arthroscopies. All were white, and all had performed physical activity at least five times a week. International Knee Documentation Committee (IKDC) and visual analog scale scores were recorded before surgery, six months and one year after surgery, and then yearly until five years after surgery. Magnetic resonance imaging scans were obtained six months preoperatively and then yearly and were evaluated by musculoskeletal radiologists blinded to the patient data. Tissue repair was quantified using the International Cartilage Repair Society morphologic score system. Unpaired t-tests were used for comparisons between the time points. RESULTS The mean preoperative IKDC score was 50.5 (42-61). At the six-month follow-up, the mean values were 60.79 (P = 0.32) and 90.97. At the six-month follow-up, the mean values were 70.8 (P = 0.043). At the end of the five-year follow-up, the IKDC was 82.2 (P = 0.024). At five-year follow-up, the visual analog scale score was 1.1 (P = 0.0018). The main morphologic score system score was 3.2 preoperatively and 9.7 ± 1.6 at five-year follow-up (P = 0.0021). No infection, tumors, or synovitis were reported at the end of the follow-up. CONCLUSIONS Intra-articular peripheral blood stem cells with platelet-rich plasma regenerated articular cartilage and improved clinical outcomes for knee chondral lesions at five years of follow-up.
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Hashimoto Y, Nishida Y, Takahashi S, Nakamura H, Mera H, Kashiwa K, Yoshiya S, Inagaki Y, Uematsu K, Tanaka Y, Asada S, Akagi M, Fukuda K, Hosokawa Y, Myoui A, Kamei N, Ishikawa M, Adachi N, Ochi M, Wakitani S. Transplantation of autologous bone marrow-derived mesenchymal stem cells under arthroscopic surgery with microfracture versus microfracture alone for articular cartilage lesions in the knee: A multicenter prospective randomized control clinical trial. Regen Ther 2019; 11:106-113. [PMID: 31312692 PMCID: PMC6610227 DOI: 10.1016/j.reth.2019.06.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 06/06/2019] [Indexed: 12/27/2022] Open
Abstract
Introduction To investigate the efficacy of the transplantation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) under arthroscopy with microfracture (MFX) compared with microfracture alone. Methods Eleven patients with a symptomatic articular cartilage defect of the knee were included in the study. They were randomized to receive BMSCs with MFX (cell-T group, n=7) or MFX alone (control group, n=4). Clinical results were evaluated using International Knee Documentation committee (IKDC) knee evaluation questionnaires and the Knee Injury and Osteoarthritis Outcome Score (KOOS) before and 48 weeks after surgery. Quantitative and qualitative assessments of repair tissue were carried out at 48 weeks by T2 mapping of magnetic resonance images (MRIs) and the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system with follow-up MRI. Results No significant differences between preoperative and postoperative IKDC and KOOS were observed in the cell-T or control group. However, forty-eight weeks after surgery, the cell-T group showed a trend for a greater KOOS QOL score compared with the control group (79.4 vs. 39.1, respectively; P=0.07). The T2 value did not differ significantly between the two groups, but the mean MOCART score was significantly higher in the cell-T group than in the control group (P=0.02). Conclusions Compared with MFX alone, BMSC transplantation with MFX resulted in better postoperative healing of the cartilage and subchondral bone as determined by the MOCART score. Clinically, BMSC transplantation with MFX gave a higher KOOS QOL score after 48 weeks.
This is the first prospective randomized clinical trial between BMSCs with MFX and MFX alone. BMSCs with MFX showed a trend for a greater KOOS QOL score compared with MFX alone. BMSCs with MFX resulted in better healing of the cartilage by the MOCART score.
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Key Words
- BMSCs, bone marrow-derived mesenchymal stem cells
- Bone marrow-derived mesenchymal stem cells
- CPC, cell processing centers
- GFP, green fluorescent protein
- HA, hyaluronic acid
- IKDC, International Knee Documentation committee
- KL, Kellgren–Lawrence
- KOOS, Knee Injury and Osteoarthritis Outcome Score
- MFX, microfracture
- MOCART, magnetic resonance observation of cartilage repair tissue
- MRIs, magnetic resonance images
- Microfracture
- Prospective randomized control clinical trial
- QOL, quality of life
- RCT, randomized controlled trial
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Affiliation(s)
- Yusuke Hashimoto
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yohei Nishida
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shinji Takahashi
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Nakamura
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Mera
- Department of Orthopaedic Surgery, Uonuma Kikan Hospital, Minamiuonuma, Japan
| | - Kaori Kashiwa
- Department of Orthopaedic Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Shinichi Yoshiya
- Department of Orthopaedic Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Yusuke Inagaki
- Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
| | - Kota Uematsu
- Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
| | - Yasuhito Tanaka
- Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
| | - Shigeki Asada
- Department of Orthopaedic Surgery, Kindai University Faculty Medicine, Osaka, Japan
| | - Masao Akagi
- Department of Orthopaedic Surgery, Kindai University Faculty Medicine, Osaka, Japan
| | - Kanji Fukuda
- Institute of Advanced Clinical Medicine, Division of Cell Biology for Regenerative Medicine, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Yoshiya Hosokawa
- Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan
| | - Akira Myoui
- Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan
| | - Naosuke Kamei
- Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences. Hiroshima University, Hiroshima, Japan
| | - Masakazu Ishikawa
- Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences. Hiroshima University, Hiroshima, Japan
| | - Nobuo Adachi
- Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences. Hiroshima University, Hiroshima, Japan
| | - Mitsuo Ochi
- Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences. Hiroshima University, Hiroshima, Japan
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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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Yanasse RH, De Lábio RW, Marques L, Fukasawa JT, Segato R, Kinoshita A, Matsumoto MA, Felisbino SL, Solano B, Dos Santos RR, Payão SLM. Xenotransplantation of human dental pulp stem cells in platelet-rich plasma for the treatment of full-thickness articular cartilage defects in a rabbit model. Exp Ther Med 2019; 17:4344-4356. [PMID: 31186677 PMCID: PMC6507499 DOI: 10.3892/etm.2019.7499] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 03/09/2018] [Indexed: 12/15/2022] Open
Abstract
Stem cells in platelet-rich plasma (PRP) scaffolds may be a promising treatment for cartilage repair. Human dental pulp stem cell (hDPSC) subpopulations have been identified to have substantial angiogenic, neurogenic and regenerative potential when compared with other stem cell sources. The present study evaluated the potential of hDPSCs in a PRP scaffold to regenerate full-thickness cartilage defects in rabbits. Full-thickness articular cartilage defects were created in the patellar groove of the femur of 30 rabbits allocated into three experimental groups: Those with an untreated critical defect (CTL), those treated with PRP (PRP) and those treated with stem cells in a PRP scaffold (PRP+SC). The patellar grooves of the femurs from the experimental groups were evaluated macroscopically and histologically at 6 and 12 weeks post-surgery. The synovial membranes were also collected and evaluated for histopathological analysis. The synovial lining cell layer was enlarged in the CTL group compared with the PRP group at 6 weeks (P=0.037) but not with the PRP+SC group. All groups exhibited low-grade synovitis at 6 weeks and no synovitis at 12 weeks. Notably, macroscopic grades for the area of articular cartilage repair for the PRP+SC group were significantly improved compared with those in the CTL (P=0.001) and PRP (P=0.049) groups at 12 weeks. Furthermore, histological scores (modified O'Driscoll scoring system) of the patellar groove articular cartilage in the PRP+SC and PRP groups, in which the articular cartilage was primarily hyaline-like, were significantly higher compared with those in the CTL group at 12 weeks (P=0.002 and P=0.007, respectively). The present results support the therapeutic use of hDPSCs for the treatment of full-thickness articular cartilage defects.
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Affiliation(s)
- Ricardo Hideki Yanasse
- Department of Genetics, Blood Center, Faculdade de Medicina de Marília (FAMEMA), Marília, SP 17519-050, Brazil
| | - Roger William De Lábio
- Department of Genetics, Blood Center, Faculdade de Medicina de Marília (FAMEMA), Marília, SP 17519-050, Brazil
| | - Leonardo Marques
- Department of Health Sciences, Universidade do Sagrado Coração, Bauru, SP 17519-050, Brazil
| | - Josianne Tomazini Fukasawa
- Department of Genetics, Blood Center, Faculdade de Medicina de Marília (FAMEMA), Marília, SP 17519-050, Brazil
| | - Rosimeire Segato
- Department of Genetics, Blood Center, Faculdade de Medicina de Marília (FAMEMA), Marília, SP 17519-050, Brazil
| | - Angela Kinoshita
- Department of Health Sciences, Universidade do Sagrado Coração, Bauru, SP 17519-050, Brazil
| | - Mariza Akemi Matsumoto
- Department of Health Sciences, Universidade do Sagrado Coração, Bauru, SP 17519-050, Brazil
| | - Sergio Luis Felisbino
- Department of Morphology, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP 17519-050, Brazil
| | - Bruno Solano
- Center for Biotechnology and Cell Therapy, Monte Tabor Hospital São Rafael, Salvador, BA 17519-050, Brazil
| | - Ricardo Ribeiro Dos Santos
- Center for Biotechnology and Cell Therapy, Monte Tabor Hospital São Rafael, Salvador, BA 17519-050, Brazil
| | - Spencer Luiz Marques Payão
- Department of Genetics, Blood Center, Faculdade de Medicina de Marília (FAMEMA), Marília, SP 17519-050, Brazil.,Department of Health Sciences, Universidade do Sagrado Coração, Bauru, SP 17519-050, Brazil
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Walter SG, Ossendorff R, Schildberg FA. Articular cartilage regeneration and tissue engineering models: a systematic review. Arch Orthop Trauma Surg 2019; 139:305-316. [PMID: 30382366 DOI: 10.1007/s00402-018-3057-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Cartilage regeneration and restoration is a major topic in orthopedic research as cartilaginous degeneration and damage is associated with osteoarthritis and joint destruction. This systematic review aims to summarize current research strategies in cartilage regeneration research. MATERIALS AND METHODS A Pubmed search for models investigating single-site cartilage defects as well as chondrogenesis was conducted and articles were evaluated for content by title and abstract. Finally, only manuscripts were included, which report new models or approaches of cartilage regeneration. RESULTS The search resulted in 2217 studies, 200 of which were eligible for inclusion in this review. The identified manuscripts consisted of a large spectrum of research approaches spanning from cell culture to tissue engineering and transplantation as well as sophisticated computational modeling. CONCLUSIONS In the past three decades, knowledge about articular cartilage and its defects has multiplied in clinical and experimental settings and the respective body of research literature has grown significantly. However, current strategies for articular cartilage repair have not yet succeeded to replicate the structure and function of innate articular cartilage, which makes it even more important to understand the current strategies and their impact. Therefore, the purpose of this review was to globally summarize experimental strategies investigating cartilage regeneration in vitro as well as in vivo. This will allow for better referencing when designing new models or strategies and potentially improve research translation from bench to bedside.
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Affiliation(s)
- Sebastian G Walter
- Clinic for Orthopedics and Trauma Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Robert Ossendorff
- Clinic for Orthopedics and Trauma Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Frank A Schildberg
- Clinic for Orthopedics and Trauma Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
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Freitag J, Norsworthy C, Wickham J, Shah K, Tenen A. High tibial osteotomy in combination with arthroscopic abrasion arthroplasty and autologous adipose-derived mesenchymal stem cell therapy in the treatment of advanced knee osteoarthritis. BMJ Case Rep 2019; 12:12/2/bcr-2018-228003. [PMID: 30733250 PMCID: PMC6381976 DOI: 10.1136/bcr-2018-228003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Osteoarthritis is a progressive and debilitating condition. An increasing number of total knee replacements are being performed under the age of 65. Improved understanding of the action of mesenchymal stem cells (MSC) has seen renewed interest in their role in cartilage repair. A 43-year-old man presented with grade IV medial compartment knee osteoarthritis. The patient underwent high tibial osteotomy (HTO) and arthroscopic abrasion arthroplasty in combination with adipose-derived MSC therapy. The patient reported improvement in pain and function as measured by validated outcome scores. Repeat MRI including T2 mapping techniques showed hyaline-like cartilage regeneration. This case highlights the potential benefit of surgical interventions including HTO in combination with MSC therapy in early-onset severe osteoarthritis. This technique may considerably delay or prevent the need for total knee replacement in young patients. Further controlled trials are needed to confirm the reproducibility of this outcome.
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Affiliation(s)
- Julien Freitag
- Charles Sturt University - Orange Campus, Orange, New South Wales, Australia.,Magellan Stem Cells, Box Hill North, Victoria, Australia.,Melbourne Stem Cell Centre, Box Hill North, Victoria, Australia
| | | | - James Wickham
- Charles Sturt University - Orange Campus, Orange, New South Wales, Australia
| | - Kiran Shah
- Magellan Stem Cells, Box Hill North, Victoria, Australia
| | - Abi Tenen
- Magellan Stem Cells, Box Hill North, Victoria, Australia.,Melbourne Stem Cell Centre, Box Hill North, Victoria, Australia.,Monash University, Clayton, Victoria, Australia
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Hurley ET, Shimozono Y, Kennedy JG. Cartilage Techniques for Osteochondral Lesions of the Talus. SPORTS INJURIES OF THE FOOT AND ANKLE 2019:105-117. [DOI: 10.1007/978-3-662-58704-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Concentrated Bone Marrow Aspirate May Decrease Postoperative Cyst Occurrence Rate in Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus. Arthroscopy 2019; 35:99-105. [PMID: 30424945 DOI: 10.1016/j.arthro.2018.06.047] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 06/15/2018] [Accepted: 06/19/2018] [Indexed: 02/02/2023]
Abstract
PURPOSE To clarify if the use of concentrated bone marrow aspirate (CBMA) would affect both postoperative functional outcomes and magnetic resonance imaging (MRI) outcomes compared with those of autologous osteochondral transplantation (AOT) alone; in addition, to assess the efficacy of CBMA reducing the presence of postoperative cyst formation following AOT in the treatment of osteochondral lesions of the talus. METHODS Fifty-four (92%) of 59 eligible patients who underwent AOT between 2004 and 2008 were retrospectively assessed at a minimum of 5-year follow-up. Twenty-eight patients were treated with AOT and CBMA (AOT/CBMA group) and 26 patients were treated with AOT alone (AOT-alone group). Clinical outcomes were evaluated using the Foot and Ankle Outcome Scores (FAOS) and Short-Form 12 (SF-12) preoperatively and at final follow-up. Postoperative MRI was evaluated with the modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. Cyst formation was also evaluated on postoperative MRI. RESULTS The mean FAOS and SF-12 significantly improved in both the AOT/CBMA and AOT-alone groups, but there were no statistical differences between groups in FAOS (80.5 vs 75.5, P = .225) and SF-12 (71.1 vs 69.6, P = .756) at final follow-up. Additionally, there was no difference in the mean MOCART score (80.4 vs 84.3, P = .484); however, AOT/CBMA did result in a statistically lower rate of cyst formation (46.4% vs 76.9%, P = .022). No significant differences were found in the mean postoperative FAOS and SF-12 between patients with and without cysts postoperatively. CONCLUSIONS CBMA reduced postoperative cyst occurrence rate in patients treated with AOT; however, CBMA did not result in significant differences in medium term functional outcomes and MOCART score in patients who underwent AOT. LEVEL OF EVIDENCE Level III, retrospective comparative trial.
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Christensen K, Cox B, Anz A. Emerging Orthobiologic Techniques and the Future. Clin Sports Med 2018; 38:143-161. [PMID: 30466719 DOI: 10.1016/j.csm.2018.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The future of orthopedic surgery appears to be intimately associated with the development of orthobiologics to facilitate healing and the treatment of multiple disease processes. The orthopedic community should understand developmental processes to ensure that products are adequately studied and the effects are fully known before widespread implementation in the clinical setting. Technologies that embrace this paradigm will impact the field the most.
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Affiliation(s)
- Kevin Christensen
- Andrews Institute, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA
| | - Benjamin Cox
- PLLC, 2890 Health Parkway, Mount Pleasant, MI 48858, USA
| | - Adam Anz
- Andrews Institute, Andrews Research and Education Foundation, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA.
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