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Cho D, Kukadia S, Kumar P, Stern J, Shamrock A, Drakos M. Comparison of Clinical Outcomes Between Cheilectomy and Proximal Phalangeal Dorsiflexion Osteotomy With and Without Bone Marrow Aspirate Concentrate and Extracellular Matrix for Hallux Rigidus. Foot Ankle Int 2025:10711007251323883. [PMID: 40129040 DOI: 10.1177/10711007251323883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
BACKGROUND Hallux rigidus with an associated osteochondral lesion is a common condition that can effectively be treated with a cheilectomy and Moberg osteotomy (CM). The use of biological adjuncts such as extracellular matrix (ECM) and bone marrow aspirate concentrate (BMAC) have been suggested to facilitate healing and restore forefoot function. The aim was to report if the addition of ECM and BMAC improves clinical outcomes for the treatment of hallux rigidus. METHODS Patients who received open cheilectomy with first proximal phalangeal dorsal closing wedge osteotomy with and without ECM and BMAC for the diagnosis of hallux rigidus between February 2016 to July 2022 by the principal investigator were reviewed. A total of 137 patients were included, 71 in the cheilectomy with Moberg osteotomy group (CM) and 66 in the cheilectomy with Moberg osteotomy and ECM/BMAC group (CM + ECM/BMAC). All patients received Patient-Reported Outcomes Measurement Information System (PROMIS) surveys preoperatively and at minimum 1 year postoperatively. Postoperative complications were also noted for the patient cohort. RESULTS The average time from surgery to final follow-up was 21.6 (range, 12-36.2) months for CM patients and 27.8 (range, 12-82.5) months for CM+BMAC patients (P = .001). Both CM and CM+BMAC cohorts demonstrated significant improvement in physical function, pain interference, pain intensity, and global physical health. However, there were no significant differences in preoperative or postoperative PROMIS domains between the 2 cohorts. CONCLUSION In conclusion, this study compares short-term patient-reported clinical outcomes and complications of cheilectomy and Moberg osteotomy against cheilectomy and Moberg osteotomy with ECM and BMAC for hallux rigidus. This study suggests that any potential differences in outcomes between groups are not large enough to be clinically meaningful in the short term and that other factors may be more relevant in determining the best course of treatment. A longer follow-up is required to evaluate long-term functional and clinical outcomes, and to see if addressing the cartilage has long-term effects.
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Affiliation(s)
- David Cho
- Hospital for Special Surgery, New York, NY, USA
| | | | | | | | | | - Mark Drakos
- Hospital for Special Surgery, New York, NY, USA
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Lana JF, de Brito GC, Kruel A, Brito B, Santos GS, Caliari C, Salamanna F, Sartori M, Barbanti Brodano G, Costa FR, Jeyaraman M, Dallo I, Bernaldez P, Purita J, de Andrade MAP, Everts PA. Evolution and Innovations in Bone Marrow Cellular Therapy for Musculoskeletal Disorders: Tracing the Historical Trajectory and Contemporary Advances. Bioengineering (Basel) 2024; 11:979. [PMID: 39451354 PMCID: PMC11504458 DOI: 10.3390/bioengineering11100979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/23/2024] [Accepted: 09/25/2024] [Indexed: 10/26/2024] Open
Abstract
Bone marrow cellular therapy has undergone a remarkable evolution, significantly impacting the treatment of musculoskeletal disorders. This review traces the historical trajectory from early mythological references to contemporary scientific advancements. The groundbreaking work of Friedenstein in 1968, identifying fibroblast colony-forming cells in bone marrow, laid the foundation for future studies. Caplan's subsequent identification of mesenchymal stem cells (MSCs) in 1991 highlighted their differentiation potential and immunomodulatory properties, establishing them as key players in regenerative medicine. Contemporary research has focused on refining techniques for isolating and applying bone marrow-derived MSCs. These cells have shown promise in treating conditions like osteonecrosis, osteoarthritis, and tendon injuries thanks to their ability to promote tissue repair, modulate immune responses, and enhance angiogenesis. Clinical studies have demonstrated significant improvements in pain relief, functional recovery, and tissue regeneration. Innovations such as the ACH classification system and advancements in bone marrow aspiration methods have standardized practices, improving the consistency and efficacy of these therapies. Recent clinical trials have validated the therapeutic potential of bone marrow-derived products, highlighting their advantages in both surgical and non-surgical applications. Studies have shown that MSCs can reduce inflammation, support bone healing, and enhance cartilage repair. However, challenges remain, including the need for rigorous characterization of cell populations and standardized reporting in clinical trials. Addressing these issues is crucial for advancing the field and ensuring the reliable application of these therapies. Looking ahead, future research should focus on integrating bone marrow-derived products with other regenerative techniques and exploring non-surgical interventions. The continued innovation and refinement of these therapies hold promise for revolutionizing the treatment of musculoskeletal disorders, offering improved patient outcomes, and advancing the boundaries of medical science.
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Affiliation(s)
- José Fábio Lana
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (G.C.d.B.); (A.K.); (B.B.)
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (I.D.); (J.P.); (P.A.E.)
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
- Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil
- Medical School, Jaguariúna University Center (UniFAJ), Jaguariúna 13820-000, SP, Brazil
| | - Gabriela Caponero de Brito
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (G.C.d.B.); (A.K.); (B.B.)
| | - André Kruel
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (G.C.d.B.); (A.K.); (B.B.)
| | - Benjamim Brito
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (G.C.d.B.); (A.K.); (B.B.)
| | - Gabriel Silva Santos
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil; (J.F.L.); (G.C.d.B.); (A.K.); (B.B.)
| | - Carolina Caliari
- Cell Therapy, In Situ Terapia Celular, Ribeirão Preto 14056-680, SP, Brazil;
| | - Francesca Salamanna
- Surgical Sciences and Technologies, IRCCS Instituto Ortopedizo Rizzoli, 40136 Bologna, Italy; (F.S.); (M.S.)
| | - Maria Sartori
- Surgical Sciences and Technologies, IRCCS Instituto Ortopedizo Rizzoli, 40136 Bologna, Italy; (F.S.); (M.S.)
| | | | - Fábio Ramos Costa
- Department of Orthopaedics, FC Sports Traumatology, Salvador 40296-210, BA, Brazil;
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr. MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India;
- Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Clinical Research Scientist, Virginia Tech India, Chennai 600095, Tamil Nadu, India
| | - Ignácio Dallo
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (I.D.); (J.P.); (P.A.E.)
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
- Orthopedics, SportMe Medical Center, 41013 Seville, Spain;
| | | | - Joseph Purita
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (I.D.); (J.P.); (P.A.E.)
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
| | | | - Peter Albert Everts
- Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil; (I.D.); (J.P.); (P.A.E.)
- Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil
- Gulf Coast Biologics, Fort Myers, FL 33916, USA
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Baek JH, Lee SC, Lee DN, Ahn HS, Nam CH. Effectiveness and Complications of Bone Marrow Aspirate Concentrate in Patients with Knee Osteoarthritis of Kellgren-Lawrence Grades II-III. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:977. [PMID: 38929594 PMCID: PMC11206007 DOI: 10.3390/medicina60060977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 06/07/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024]
Abstract
This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren-Lawrence (K-L) grades II-III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K-L grades II-III OA. The exclusion criteria were age of <40 years or >80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6-8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up (p < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 (p < 0.05) and from 68.4 to 83.3 points (p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K-L grades II-III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.
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Affiliation(s)
| | | | | | | | - Chang Hyun Nam
- Joint & Arthritis Research, Department of Orthopaedic Surgery, Himchan Hospital, Seoul 07999, Republic of Korea; (J.-H.B.); (S.C.L.); (D.N.L.); (H.S.A.)
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Perez OF, Warburton C, Philippon MC, Philippon MJ, Best TM. The Efficacy of Bone Marrow Stem Cell Therapy in Hip Osteoarthritis: A Scoping Review. HSS J 2024:15563316241259035. [PMID: 39564400 PMCID: PMC11572593 DOI: 10.1177/15563316241259035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 05/07/2024] [Indexed: 11/21/2024]
Abstract
Background Hip osteoarthritis (HOA) is a prevalent degenerative joint disease with various treatment approaches. Biological agents, such as bone-marrow derived stem cells (BM-MSC) therapy, have recently been proposed as a treatment option in the management of HOA. Purpose We sought to further analyze the use of BM-MSC therapy by investigating the following questions. What is the standard preparation and practice? Does a dose response exist between stem cell therapy and clinical outcome? Does BM-MSC therapy alone produce effective clinical outcomes? Methods We conducted a scoping review using the Methodological Expectations of Cochrane Intervention Reviews Manual and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping reviews. A comprehensive search of PubMed, Embase, Cochrane CENTRAL, Scopus, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Core Collection was performed in June 2023 of studies using exclusively BM-MSC injections for the treatment of HOA. Study characteristic, injection preparation and dosage, clinical outcome measures, and adverse effect data were extracted and interpreted by 3 reviewers. Results Seven studies with a total of 72 patients met the inclusion criteria. Clinical outcome following intra-articular injection of BM-MSCs was measured using the numerical pain scale, the Western Ontario and McMaster Universities Osteoarthritis Index, the visual analogue scale, and other scores, all of which showed reduction in pain and increase in functional ability across studies. Conclusions This scoping review found that the efficacy of BM-MSC therapy alone in the treatment of HOA appeared beneficial, improving clinical outcomes in each study. All 7 studies used "low-dose" injections with variable follow-up times; thus, a clear dose-response relationship cannot be drawn. Future studies using high doses and analyzing long-term effects of BM-MSC injections in HOA are needed.
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Affiliation(s)
- Olivia F Perez
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | | | | | - Marc J Philippon
- Center for Regenerative and Personalized Medicine (CRPM), Steadman Philippon Research Institute, Vail, CO, USA
| | - Thomas M Best
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
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Altomare D, Di Matteo B, Kon E. Conservative Treatment for Ankle Cartilage: Cellular and Acellular Therapies: A Systematic Review. Foot Ankle Clin 2024; 29:253-263. [PMID: 38679437 DOI: 10.1016/j.fcl.2023.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/01/2024]
Abstract
Biological agents like growth factors (ie, platelet rich plasma) and mesenchymal stem cells are rising in popularity among orthopedics. Orthobiologics therapy aims to fill the gap between conventional conservative therapies like hyaluronic acid and surgery, especially for cartilage disease. Ankle cartilage defects are very symptomatic and could lead to a severe decrease of quality of life in patients, because of pain, swelling, and inability to walk without pain. In this scenario, this paper aims to systematically review the current literature available about biological therapies for ankle cartilage.
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Affiliation(s)
- Daniele Altomare
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20090, Italy; Department of Orthopaedics and Traumatology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, Milan 20089, Italy.
| | - Berardo Di Matteo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20090, Italy; Department of Orthopaedics and Traumatology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, Milan 20089, Italy; Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov University, Moscow, 119991, Russia
| | - Elizaveta Kon
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20090, Italy; Department of Orthopaedics and Traumatology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, Milan 20089, Italy; Department of Traumatology, Orthopaedics and Disaster Surgery, Sechenov University, Moscow, 119991, Russia
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Fortier LA. Equine Bone Marrow Aspirate Concentrate. Vet Clin North Am Equine Pract 2023; 39:453-459. [PMID: 37442728 DOI: 10.1016/j.cveq.2023.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/15/2023] Open
Abstract
Bone marrow concentrate is generated by centrifugation of bone marrow aspirate. It contains mesenchymal stromal cells, anabolic chemokines/cytokines, and supraphysiological concentrations of interleukin-1 receptor antagonist protein (IL-1RA). It is an effective treatment for osteoarthritis or desmitis, or as an adjunct in surgery to enhance bone or cartilage repair.
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Affiliation(s)
- Lisa A Fortier
- Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, USA.
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Mariani C, Meneghetti E, Zambon D, Elena N, Agueci A, Melchior C. Use of bone marrow derived mesenchymal stem cells for the treatment of osteoarthritis: A retrospective long-term follow-up study. J Clin Orthop Trauma 2023; 36:102084. [PMID: 36561706 PMCID: PMC9763840 DOI: 10.1016/j.jcot.2022.102084] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/23/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Background Available studies suggest that bone marrow concentrate, highly enriched in mesenchymal stem cells, is a potentially encouraging treatment for knee osteoarthritis. The aim of this retrospective study was to evaluate the clinical outcome in patients affected by this condition after treatment with autologous bone marrow aspirate concentrate (BMAC). Methods 55 patients who had undergone a single intra-articular injection of BMAC were administered two questionnaires to clinically evaluate their condition based on patient-reported outcome measures before treatment and at follow-up. Results Analysis of the data collected indicates that patients experienced improvements in Tegner, VAS and WOMAC scores and that all outcomes at the follow-up improved in a statistically significant manner compared to outcomes at baseline. Conclusions The changes observed in the different scores examined suggest that a single BMAC injection seems to be a beneficial and safe treatment for knee osteoarthritis.
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Affiliation(s)
- Cesare Mariani
- U.O.C. of Orthopedics and Trauma Surgery – PP.OO, Conegliano e Vittorio Veneto, AULSS 2 Marca Trevigiana, Italy
| | - Ezio Meneghetti
- U.O.C. of Orthopedics and Trauma Surgery – PP.OO, Conegliano e Vittorio Veneto, AULSS 2 Marca Trevigiana, Italy
| | - Doriano Zambon
- U.O.C. of Orthopedics and Trauma Surgery – PP.OO, Conegliano e Vittorio Veneto, AULSS 2 Marca Trevigiana, Italy
| | - Nicholas Elena
- Department of Orthopedics and Trauma Surgery, University of Verona, Italy
| | - Alberto Agueci
- U.O.C. of Orthopedics and Trauma Surgery – PP.OO, Conegliano e Vittorio Veneto, AULSS 2 Marca Trevigiana, Italy
| | - Claudio Melchior
- U.O.C. of Orthopedics and Trauma Surgery – PP.OO, Conegliano e Vittorio Veneto, AULSS 2 Marca Trevigiana, Italy
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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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Rackwitz L, Pullig O, Nöth U. Stammzelltherapie in Deutschland. ARTHROSKOPIE 2022. [DOI: 10.1007/s00142-022-00562-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Keeling LE, Belk JW, Kraeutler MJ, Kallner AC, Lindsay A, McCarty EC, Postma WF. Bone Marrow Aspirate Concentrate for the Treatment of Knee Osteoarthritis: A Systematic Review. Am J Sports Med 2022; 50:2315-2323. [PMID: 34236913 DOI: 10.1177/03635465211018837] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Bone marrow aspirate concentrate (BMAC) has emerged as a therapeutic option for symptomatic knee osteoarthritis (OA). PURPOSE To systematically review the literature to evaluate the efficacy of isolated BMAC injection in the treatment of OA of the knee joint. STUDY DESIGN Systematic review; Level of evidence, 4. METHODS A systematic review was performed by searching the PubMed, Embase, and Cochrane Library databases up to July 2020 to identify human studies that assessed the clinical outcomes of isolated BMAC injection for the treatment of knee OA. The electronic search strategy used was "bone marrow aspirate concentrate knee osteoarthritis." RESULTS Eight studies met the inclusion criteria, including a total of 299 knees with a mean follow-up of 12.9 months (range, 6-30 months). Of all patient-reported outcomes assessed across studies, 34 of 36 (94.4%) demonstrated significant improvement from baseline to latest follow-up (P < .05). Five studies evaluating numerical pain scores (visual analog scale and Numeric Rating Scale) reported significant improvements in pain level at final follow-up (P < .01). However, 3 comparative studies evaluating BMAC in relation to other therapeutic injections failed to demonstrate the clinical superiority of BMAC. CONCLUSION The BMAC injection is effective in improving pain and patient-reported outcomes in patients with knee OA at short- to midterm follow-up. Nevertheless, BMAC has not demonstrated clinical superiority in relation to other biologic therapies commonly used in the treatment of OA, including platelet-rich plasma and microfragmented adipose tissue, or in relation to placebo. The high cost of the BMAC injection in comparison with other biologic and nonoperative treatment modalities may limit its utility despite demonstrable clinical benefit.
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Affiliation(s)
- Laura E Keeling
- Department of Orthopaedics, MedStar Georgetown University Hospital, Washington, DC, USA
| | - John W Belk
- Department of Orthopedics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Matthew J Kraeutler
- Department of Orthopaedic Surgery, St Joseph's University Medical Center, Paterson, New Jersey, USA
| | | | - Adam Lindsay
- Department of Orthopedics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Eric C McCarty
- Department of Orthopedics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - William F Postma
- Department of Orthopaedics, MedStar Georgetown University Hospital, Washington, DC, USA
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Anz A, Sherman B. Concentrated Bone Marrow Aspirate Is More Cellular and Proliferative When Harvested From the Posterior Superior Iliac Spine Than the Proximal Humerus. Arthroscopy 2022; 38:1110-1114. [PMID: 34715280 DOI: 10.1016/j.arthro.2021.10.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 10/12/2021] [Accepted: 10/16/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study is to determine whether concentrated bone marrow aspirate (cBMA) from the posterior superior iliac spine (PSIS) or proximal humerus (PH) produces a more productive cellular harvest in patients undergoing arthroscopic rotator cuff repair. METHODS Patients under 80 years old undergoing surgery for arthroscopic rotator cuff repair were enrolled. Two 60 mL aliquots of BMA were harvested from each subject, one from the PSIS and one from the PH. Each aliquot was processed independently to create cBMA. Cellular composition was determined using an automated hemocytometer and proliferative potential was studied with colony forming unit (CFU) assays. RESULTS Twelve patients were recruited (7 male, 5 female). The average age was 64.3 years (range 46.1-77.25 years) with body mass index of 26.8 (range 20.0-34.3). The average total nucleated cells (TNC) from PH was 18.7 × 106 cells/mL (95% confidence interval [CI], 4.4-33.0; standard deviation [SD], 24.8) with 3.9 CFU/mL (95% CI, 0.3-7.5, SD, 5.7). The average TNC count from the PSIS was 55.9 × 106 cells/mL (95% CI, 25.3-86.4; SD, 52.9) with 32.5 CFU/mL (95% CI, 11.5-53.5; SD, 33.1). The PSIS had a 3.0 times greater total nucleated cell yield (P = .014) and 8.3 times greater number of CFU/mL (P = .024) when compared to the PH. The average harvest time from the PSIS was 5.6 minutes and from the PH was 11.0 minutes (P = .043); harvest time did not account for additional time to prep and drape the PSIS. CONCLUSIONS The cBMA harvested from the PSIS resulted in a 3.0 times greater cellular yield and an 8.3 times greater proliferative product than cBMA from the PH. CLINICAL RELEVANCE When a more cellular cBMA product is sought to augment rotator cuff tear repair surgery, the PSIS is the preferred site for harvest.
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Affiliation(s)
- Adam Anz
- Andrews Research & Education Foundation, Gulf Breeze, Florida, U.S.A.
| | - Benjamin Sherman
- Andrews Research & Education Foundation, Gulf Breeze, Florida, U.S.A
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Methodological Flaws in Meta-Analyses of Clinical Studies on the Management of Knee Osteoarthritis with Stem Cells: A Systematic Review. Cells 2022; 11:cells11060965. [PMID: 35326416 PMCID: PMC8946093 DOI: 10.3390/cells11060965] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 12/13/2022] Open
Abstract
(1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. (2) Methods: PubMed, Web of Science, and the Cochrane Library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. (3) Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the comparability of different types of stem cells with regard to their safety and regenerative potential. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. (4) Conclusions: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy.
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Vannini F, Zielli SO, Faldini C. Cartilage Lesions and Osteoarthritis of the Hip and Ankle: Orthobiologics. ORTHOBIOLOGICS 2022:329-348. [DOI: 10.1007/978-3-030-84744-9_27] [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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Brozovich A, Sinicrope BJ, Bauza G, Niclot FB, Lintner D, Taraballi F, McCulloch PC. High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique. Orthop J Sports Med 2021; 9:23259671211058459. [PMID: 34901292 PMCID: PMC8655450 DOI: 10.1177/23259671211058459] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 08/24/2021] [Indexed: 12/28/2022] Open
Abstract
Background: Bone marrow aspirate (BMA) is a common source for harvesting mesenchymal stem cells (MSCs), other progenitor cells, and associated cytokines and growth factors to be used in the biologic treatment of various orthopaedic pathologies. The aspirate is commonly centrifuged into a concentrated volume that can be immediately administered to a patient using commercially available kits. However, the handling and efficacy of BMA concentrate (BMAC) are still controversial. Purpose: To characterize BMA versus BMAC for MSC quantity, potency, and cytokine profile. Study Design: Controlled laboratory study. Methods: From 8 participants (age, 17-68 years), 30 mL of bone marrow was aspirated by a single surgeon from either the proximal humerus or distal femur and was separated into 2 equal samples. One sample was kept as BMA, and the other half was centrifuged into BMAC. The 2 samples then underwent flow cytometry for detection of MSCs, cell analysis for colony-forming units (CFUs), and cytokine profiling. A 2-tailed t test was used to detect differences between MSCs, CFUs, and cytokine density concentrations between BMA and BMAC. Results: The average concentration of MSCs in both BMA and BMAC was 0.001%. Average MSC events detected by flow cytometry were significantly higher in BMA versus BMAC (15.1 and 8.1, respectively; P < .045). Expanded MSCs demonstrated similar phenotypes, but CFUs were significantly increased in BMA compared with BMAC (104 vs 68 CFUs, respectively; P < .001). Total protein concentration and cytokine profiling demonstrated great variability between BMA and BMAC and between patients. Most importantly, BMAC failed to concentrate MSCs in 6 of 8 samples. Conclusion: There is great variability in MSC concentration, total protein concentration, and cytokine profile between BMA and BMAC. Clinical Relevance: When studying the clinical efficacy of BMAC, one must also evaluate the sample itself to determine the presence, concentration, and potency of MSCs if this is to be considered a cell-based therapy. Further standard operating procedures need to be investigated to ensure reproducible results and appropriate treatments.
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Affiliation(s)
- Ava Brozovich
- Texas A&M College of Medicine, Bryan, Texas, USA.,Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA.,Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Brent J Sinicrope
- Orthopaedic Surgery, King's Daughters' Health, Madison, Indiana, USA
| | - Guillermo Bauza
- Center for NanoHealth, Swansea University Medical School, Swansea, Wales, UK
| | | | - David Lintner
- Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Francesca Taraballi
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA.,Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Patrick C McCulloch
- Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
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Bone marrow aspirate concentrate and scaffold for osteochondral lesions of the talus in ankle osteoarthritis: satisfactory clinical outcome at 10 years. Knee Surg Sports Traumatol Arthrosc 2021; 29:2504-2510. [PMID: 33606047 DOI: 10.1007/s00167-021-06494-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 02/05/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE To evaluate at long-term follow-up patients undergoing a one-step procedure of debridement and BMAC seeded in situ onto a scaffold for the treatment of osteochondral lesions of the talus (OLT) in ankles affected by osteoarthritis (OA), documenting the duration of the clinical benefit and its efficacy in postponing end-stage procedures. METHODS This series included 56 consecutive patients. Patients were evaluated preoperatively and up to a mean of 10 years of follow-up with the AOFAS score and the AOS scale, including pain and disability subscales. Furthermore, patients were asked to rate the satisfaction and failures were documented as well. RESULTS The AOFAS score improved from 52.3 ± 14.3 to 73.5 ± 23.1 at 10 years (p < 0.0005); the AOS pain and disability subscales decreased from 70.9 ± 14.1 to 37.2 ± 32.7 and from 69.0 ± 14.8 to 34.2 ± 29.3, respectively (both p < 0.0005). The overall rate of satisfaction was 61.8 ± 41.2 and 68.6% of patients would undergo again the surgical procedure. A total of 17 failures was documented, for a failure rate of 33.3%. Older patients and those with more complex cases requiring previous or combined surgeries had lower outcomes, as well as those affected by grade 3 OA, who experienced a high failure rate of 71.4%. CONCLUSIONS This one-step technique for the treatment of OLT in OA ankles showed to be safe and to provide a satisfactory outcome, even if patients with end stage OA presented a high revision rate at 10 years. Moreover, this procedure was effective over time, with overall good results maintained up to a long-term follow-up. However, older age, more complex cases requiring previous or combined surgeries, and advanced OA led to an overall worst outcome and a significantly higher failure rate.
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Cole BJ, Gilat R, DiFiori J, Rodeo SA, Bedi A. The 2020 NBA Orthobiologics Consensus Statement. Orthop J Sports Med 2021; 9:23259671211002296. [PMID: 34017878 PMCID: PMC8114275 DOI: 10.1177/23259671211002296] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 12/14/2020] [Indexed: 12/26/2022] Open
Abstract
This 2020 NBA Orthobiologics Consensus Statement provides a concise summary of available literature and practical clinical guidelines for team physicians and players. We recognize that orthobiologic injections are a generally safe treatment modality with a significant potential to reduce pain and expedite early return to play in specific musculoskeletal injuries. The use of orthobiologics in sports medicine to safely reduce time loss and reinjury is of considerable interest, especially as it relates to the potential effect on a professional athlete. While these novel substances have potential to enhance healing and regeneration of injured tissues, there is a lack of robust data to support their regular use at this time. There are no absolutes when considering the implementation of orthobiologics, and unbiased clinical judgment with an emphasis on player safety should always prevail. Current best evidence supports the following: Key Points There is support for the use of leukocyte-poor platelet-rich plasma in the treatment of knee osteoarthritis. There is support for consideration of using leukocyte-rich platelet-rich plasma for patellar tendinopathy. The efficacy of using mesenchymal stromal cell injections in the management of joint and soft tissue injuries remains unproven at this time. There are very few data to suggest that current cell therapy treatments lead to any true functional tissue regeneration. Meticulous and sterile preparation guidelines must be followed to minimize the risk for infection and adverse events if these treatments are pursued.Given the high variability in orthobiologic formulations, team physicians must stay up-to-date with the most recent peer-reviewed literature and orthobiologic preparation protocols for specific injuries.Evidence-based treatment algorithms are necessary to identify the optimal orthobiologic formulations for specific tissues and injuries in athletes.Changes in the regulatory environment and improved standardization are required given the exponential increase in utilization as novel techniques and substances are introduced into clinical practice.
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Affiliation(s)
- Brian J Cole
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA
| | - Ron Gilat
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, USA.,Department of Orthopaedic Surgery, Shamir Medical Center and Tel Aviv University, Tel Aviv, Israel
| | - John DiFiori
- Hospital for Special Surgery, New York, New York, USA
| | - Scott A Rodeo
- Hospital for Special Surgery, New York, New York, USA
| | - Asheesh Bedi
- Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA
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Autologous Bone Marrow Cell Therapy for the Knee: Are We There Yet? OPER TECHN SPORT MED 2020. [DOI: 10.1016/j.otsm.2020.150777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Whitney KE, Briggs KK, Chamness C, Bolia IK, Huard J, Philippon MJ, Evans TA. Bone Marrow Concentrate Injection Treatment Improves Short-term Outcomes in Symptomatic Hip Osteoarthritis Patients: A Pilot Study. Orthop J Sports Med 2020; 8:2325967120966162. [PMID: 33344667 PMCID: PMC7731709 DOI: 10.1177/2325967120966162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 06/12/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Osteoarthritis (OA) is one of the leading causes of disability in the United States, the hip being the second most affected weightbearing joint. Autologous bone marrow concentrate (BMC) is a promising alternative therapy to conventional treatments, with the potential to mitigate inflammation and improve joint function. PURPOSE To investigate the effectiveness of a single intra-articular BMC injection for patients with symptomatic hip OA. STUDY DESIGN Case series; Level of evidence, 4. METHODS A total of 24 patients diagnosed with symptomatic hip OA who elected to undergo a single BMC injection were prospectively enrolled in the study. Patients were excluded if they reported a preinjection Numeric Rating Scale (NRS) score for pain with activity of <6 points out of 10. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), 12-Item Short Form Health Survey (SF-12), and NRS pain scores were collected before and after the procedure (6 weeks, 3 months, and 6 months). Joint space and Tönnis OA grade scores were recorded on preinjection anteroposterior pelvis radiographs. RESULTS A total of 18 hips from 16 patients (7 male and 9 female) (mean age, 57.6 ± 11; mean body mass index, 25.9 ± 3.6 kg/m2) were used in the final analysis. Significant improvements were observed in NRS pain with activity (from 8 to 4.5; P < .001) and without activity (from 5 to 1; P < .001), WOMAC (from 31 to 16; P = .006), mHHS (from 63 to 80; P = .004), and HOS-ADL (from 71 to 85; P = .014) over 6 months. At 6 months, all patients maintained their improvements and did not return to preprocedure status. BMI significantly correlated with baseline WOMAC scores (P = .012) and inversely correlated with 6-month SF-12 Physical Component Summary (P = .038). Tönnis grades 2 and 3 were inversely correlated with 6-week SF-12 Mental Component Summary (P = .008) and 3-month pain with activity (P = .032). No serious adverse events were reported from the BMC harvest or injection procedure. CONCLUSION A single BMC injection can significantly improve subjective pain and function scores up to 6 months in patients with symptomatic hip OA. Further studies are warranted to evaluate BMC treatment against other therapeutics in a larger sample size and compare the biological signature profiles that may be responsible for the therapeutic effect.
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Affiliation(s)
- Kaitlyn E. Whitney
- The Steadman Clinic, Vail, Colorado, USA
- Steadman Philippon Research Institute, Vail, Colorado, USA
| | | | | | | | - Johnny Huard
- Steadman Philippon Research Institute, Vail, Colorado, USA
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Quantification and Qualification of Stem Cells From Blood After Mobilization With Filgrastim, and Concentration Using a Platelet-Rich Plasma System. Arthroscopy 2020; 36:2911-2918. [PMID: 32679293 DOI: 10.1016/j.arthro.2020.07.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 06/25/2020] [Accepted: 07/01/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To determine the cellular composition of a product created with peripheral blood harvested after systemic mobilization with filgrastim and processed with one point-of-care blood concentrating system, i.e., a platelet-rich plasma (PRP) system. The second purpose was to compare mobilized platelet-rich plasma (M-PRP) with a concentrated bone marrow aspirate (cBMA) and a PRP created from the same subjects with the same PRP system. METHODS Ten healthy volunteer subjects were recruited for collection and analysis of 3 tissue sources: non-treated peripheral blood, bone marrow aspirate, and filgrastim-mobilized peripheral blood, involving 4 doses of weight-based filgrastim. One point-of-care blood and bone marrow concentrating system was used to create 3 products: PRP, cBMA, and M-PRP. Automated hematologic analysis was performed on all products to quantify total red blood cells, white blood cells (WBCs), monocyte, platelet, and hematopoietic progenitor cell (HPC) concentrations. Flow cytometry was used to determine hematopoietic and mesenchymal progenitor cell populations. Lastly, concentrates were cultured and fibroblast colony-forming units (CFU-F) and morphology of adherent cells were evaluated. RESULTS M-PRP contained a greater concentration of WBC (mean difference = 53.2 k/μL; P < .0001), monocytes (mean difference = 8.3 k/μL; P = .002), and a trend toward a greater concentration of HPC (mean difference = 200.5 /μL; P = .060) when compared with PRP. M-PRP contained a greater concentration of monocytes (mean difference = 5.5 k/μL; P = .017) and a trend toward a greater concentration of platelets (mean difference = 348 k/μL; P = .051) and HPC (mean difference = 193.4 /μL; P = .068) when compared with cBMA. M-PRP had a similar concentration of platelets to PRP (mean difference = 110 k/μL; P = .051) and PRP had a greater concentration than cBMA (mean difference = 458 k/μL; P = .003). cBMA remained the only product capable of producing CFU-Fs (446 ± 247 /mL) as neither the M-PRP nor PRP produced CFU-Fs. M-PRP produced colonies consistent with WBC. CONCLUSIONS M-PRP, produced with filgrastim mobilized blood and a proprietary PRP system, contained more total WBCs, monocytes, platelets, and HPCs than cBMA and more WBCs, monocytes, and HPCs than PRP. CLINICAL RELEVANCE Filgrastim mobilized PRP may be an alternative to cBMA for use as a point-of-care product for orthopaedic treatments.
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Morikawa D. Editorial Commentary: Human Granulocyte-Stimulating Factor Increases the Leukocyte Richness of Platelet-Rich Plasma. Arthroscopy 2020; 36:2919-2920. [PMID: 33172588 DOI: 10.1016/j.arthro.2020.08.020] [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: 08/12/2020] [Accepted: 08/20/2020] [Indexed: 02/02/2023]
Abstract
Platelet-rich plasma (PRP) is the most common treatment in orthobiologis, because PRP is safe, low cost, and minimally invasive and could be used to promote the tissue-repair process. The systemic mobilization with human granulocyte-stimulating factor increased concentrations of white blood cells and monocyte but not platelets in PRP. It may enhance the efficacy of PRP therapy via monocytes/macrophages. Improving the efficacy of PRP therapy, bone marrow aspirate, mesenchymal stems cells, or other orthobiologics is not simple because there are many variations in products and patient factors.
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Biological strategies for osteoarthritis: from early diagnosis to treatment. INTERNATIONAL ORTHOPAEDICS 2020; 45:335-344. [PMID: 33078204 DOI: 10.1007/s00264-020-04838-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 09/28/2020] [Indexed: 12/20/2022]
Abstract
PURPOSE To provide an updated review of the literature on the use of orthobiologics as a potential treatment option to alleviate symptoms associated with osteoarthritis (OA), slow the progression of the disease, and aid in cartilage regeneration. METHODS A comprehensive review of the literature was performed to identify basic science and clinical studies examining the role of orthobiologics in the diagnosis and management of osteoarthritis. RESULTS Certain molecules (such as interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase (MMPs), cartilage oligomeric matrix protein (COMP), and tumor necrosis factor (TNF), microRNAs, growth differentiation factor 11 (GDF-11)) have been recognized as biomarkers that are implicated in the pathogenesis and progression of degenerative joint disease (DJD). These biomarkers have been used to develop newer diagnostic applications and targeted biologic therapies for DJD. Local injection therapy with biologic agents such as platelet-rich plasma or stem cell-based preparations has been associated with significant improvement in joint pain and function in patients with OA and has increased in popularity during the last decade. The combination of PRP with kartogenin or TGF-b3 may also enhance its biologic effect. The mesenchymal stem cell secretome has been recognized as a potential target for the development of OA therapies due to its role in mediating the chondroprotective effects of these cells. Recent experiments have also suggested the modification of gut microbiome as a newer method to prevent OA or alter the progression of the disease. CONCLUSIONS The application of orthobiologics for the diagnosis and treatment of DJD is a rapidly evolving field that will continue to expand. The identification of OA-specific and joint-specific biomarker molecules for early diagnosis of OA would be extremely useful for the development of preventive and therapeutic protocols. Local injection therapies with HA, PRP, BMAC, and other stem cell-based preparations are currently being used to improve pain and function in patients with early OA or those with progressed disease who are not surgical candidates. Although the clinical outcomes of these therapies seem to be promising in clinical studies, future research will determine the true role of orthobiologic applications in the field of DJS.
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Positive early clinical outcomes of bone marrow aspirate concentrate for osteoarthritis using a novel fenestrated trocar. Knee 2020; 27:1627-1634. [PMID: 33010782 DOI: 10.1016/j.knee.2020.08.018] [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] [Received: 01/15/2020] [Revised: 06/29/2020] [Accepted: 08/23/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND This study sought to assess early clinical outcomes for knee osteoarthritis (OA) patients undergoing bone marrow aspirate concentrate (BMAC) treatment using a novel closed-end, fenestrated trocar (FT) that does not require centrifugation. METHODS A prospective cohort of 17 knee OA patients undergoing BMAC treatment with the FT system from March 2018 to March 2019 was retrospectively evaluated. Approximately 10 mL of BMAC was harvested, no centrifugation was performed, and the BMAC was injected into the affected knee. Clinical outcomes were assessed at baseline, six weeks, and 12 weeks. This study has no affiliation with/vested-interest in the FT system. RESULTS There were significant improvements in nearly all outcomes from baseline to 12 weeks. Specific improvements included Knee Injury and OA Outcome Score (KOOS) activities-of-daily-living (61.1 ± 9.2 [mean ± 95% confidence interval] to 89.3 ± 6, p = 0.001), quality-of-life (32.7 ± 9.3 to 66.1 ± 17.9, p = 0.003), sports/recreation (36.9 ± 10.6 to 72.6 ± 26.3, p = 0.006), and pain (53.8 ± 9.3 to 83 ± 10.2, p = 0.001); Lysholm scores (55.5 ± 8.4 to 77.3 ± 10.5, p = 0.009); and visual analog pain scores (5.68 ± 1.14 to 2.07 ± 1.86, p = 0.003). Individually, at least 75% of patients exhibited improvement in all KOOS categories at six weeks and at least 85% at 12 weeks. CONCLUSIONS BMAC treatment with an FT system that does not require centrifugation resulted in significant improvements in early pain and function scores for knee OA. The symptomatic improvements in this study were similar to or greater than what has been reported using traditional needles. These data may provide clinicians with comfort in using an FT system and provide motivation for future randomized-controlled trials comparing aspiration techniques.
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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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Evidence on ankle injections for osteochondral lesions and osteoarthritis: a systematic review and meta-analysis. INTERNATIONAL ORTHOPAEDICS 2020; 45:509-523. [PMID: 32647968 DOI: 10.1007/s00264-020-04689-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 06/26/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE To evaluate the evidence supporting safety and effectiveness of intra-articular injective treatments for ankle lesions ranging from osteochondral lesions of the talus (OLT) to osteoarthritis (OA). METHODS A systematic review and a meta-analysis were performed on PubMed, Embase, and Cochrane Library in March 2020. Safety was evaluated through the reported side effects and effectiveness through the scores used. The quality of the studies was assessed using the Cochrane Collaboration Risk of Bias 2.0 tool and the Downs and Black checklist. For each outcome, the quality of evidence was graded according to GRADE guidelines. RESULTS Twenty-four studies (21 for OA, 3 for OLT) were included on hyaluronic acid (HA), platelet-rich plasma (PRP), saline, methylprednisolone, botulinum toxin type A (BoNT-A), mesenchymal stem cells (MSCs), and prolotherapy. No severe adverse events were reported. For OLT, a comparison was possible between HA and PRP showing no significant difference. For ankle OA, a significant difference favouring HA versus saline was documented at six months (p < 0.001). The GRADE level of evidence was very low. CONCLUSION This meta-analysis supports the safety of intra-articular treatment for ankle OA and OLT, while only a very low evidence supports the efficacy of HA in terms of better results versus placebo for the treatment of ankle OA, and other conclusions are hindered by the scarcity of the available literature. This urges further and stronger trials to specifically investigate potential and limitations of these different injective approaches for the treatment of OLT and ankle OA.
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Kim GB, Seo MS, Park WT, Lee GW. Bone Marrow Aspirate Concentrate: Its Uses in Osteoarthritis. Int J Mol Sci 2020; 21:3224. [PMID: 32370163 PMCID: PMC7247342 DOI: 10.3390/ijms21093224] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/30/2020] [Accepted: 05/01/2020] [Indexed: 11/16/2022] Open
Abstract
Human bone marrow (BM) is a kind of source of mesenchymal stem cells (MSCs) as well as growth factors and cytokines that may aid anti-inflammation and regeneration for various tissues, including cartilage and bone. However, since MSCs in BM usually occupy only a small fraction (0.001%) of nucleated cells, bone marrow aspirate concentrate (BMAC) for cartilage pathologies, such as cartilage degeneration, defect, and osteoarthritis, have gained considerable recognition in the last few years due to its potential benefits including disease modifying and regenerative capacity. Although further research with well-designed, randomized, controlled clinical trials is needed to elucidate the exact mechanism of BMAC, this may have the most noteworthy effect in patients with osteoarthritis. The purpose of this article is to review the general characteristics of BMAC, including its constituent, action mechanisms, and related issues. Moreover, this article aims to summarize the clinical outcomes of BMAC reported to date.
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Affiliation(s)
- Gi Beom Kim
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea; (G.B.K.); (W.T.P.)
| | - Min-Soo Seo
- Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea;
| | - Wook Tae Park
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea; (G.B.K.); (W.T.P.)
| | - Gun Woo Lee
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea; (G.B.K.); (W.T.P.)
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Purita J, Lana JFSD, Kolber M, Rodrigues BL, Mosaner T, Santos GS, Caliari-Oliveira C, Huber SC. Bone marrow-derived products: A classification proposal - bone marrow aspirate, bone marrow aspirate concentrate or hybrid? World J Stem Cells 2020; 12:241-250. [PMID: 32399133 PMCID: PMC7202927 DOI: 10.4252/wjsc.v12.i4.241] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 02/07/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Degenerative musculoskeletal disorders are one of the top causes of pain and disability in the adult population. Current available alternatives to mitigate symptoms include conservative treatments such as the administration of pharmacological agents and an educative approach towards lifestyle modification. The use of certain analgesics, such as opiates and corticosteroids, delivers short term results but do not address the etiological source of pain and disability. Also, prolonged use of such medications may cause additional complications. Therefore, the demand for musculoskeletal tissue regeneration has led to an alternative approach referred to as "orthobiologics". This alternative is based on cellular and molecular components capable of inducing and promoting tissue repair. Bone marrow (BM) aspirate (BMA) and concentrate are well-known orthobiologics used to treat musculoskeletal conditions. Orthobiologics derived from the BM have been discussed in the literature; however, the lack of standardization regarding collection and processing protocols presents a challenge for generalization of study outcomes and determination of efficacy. Since BM-derived orthobiologics have not yet been classified, to our knowledge, this manuscript proposes the ACH classification system, which speaks to BMA (A), BMA and concentrate (C) and hybrid (H), which combines A and C. This classification proposes and describes 8 parameters that are relevant for the quality of biological products. The more parameters used would imply greater characterization and complexity of the evaluation of the biological product used. The ACH classification envisages a necessary contribution to the comprehension of both clinical procedures and research outcomes, ultimately ushering in a standardization of best practice.
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Affiliation(s)
- Joseph Purita
- Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
| | | | - Morey Kolber
- Department of Physical Therapy, Nova Southeastern University, Fort Lauderdale, FL 33314, United States
| | | | - Tomas Mosaner
- Institute of Bone and Cartilage, Indaiatuba, SP 13334-170, Brazil
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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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Kolber MJ, Purita J, Sterling B, Stermer J, Salamh P, Masaracchio M, Hanney WJ. Stem Cell Injections for Musculoskeletal Pathology: An Overview for the Sports Medicine Professional. Strength Cond J 2019. [DOI: 10.1519/ssc.0000000000000500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Ziegler CG, Van Sloun R, Gonzalez S, Whitney KE, DePhillipo NN, Kennedy MI, Dornan GJ, Evans TA, Huard J, LaPrade RF. Characterization of Growth Factors, Cytokines, and Chemokines in Bone Marrow Concentrate and Platelet-Rich Plasma: A Prospective Analysis. Am J Sports Med 2019; 47:2174-2187. [PMID: 31034242 DOI: 10.1177/0363546519832003] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and other bioactive molecules. Before the clinical utility of PRP and BMC is optimized as a combined therapy or monotherapy, an improved understanding of the components and respective concentrations is necessary. PURPOSE To prospectively measure and compare anabolic, anti-inflammatory, and proinflammatory growth factors, cytokines, and chemokines in bone marrow aspirate (BMA), BMC, whole blood, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) from samples collected and processed concurrently on the same day from patients presenting for elective knee surgery. STUDY DESIGN Cross-sectional study; Level of evidence, 3. METHODS Patients presenting for elective knee surgery were prospectively enrolled over a 3-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed via centrifugation and manual extraction methods to prepare LR-PRP, LP-PRP, and BMC samples, respectively. BMA, BMC, whole blood, LR-PRP, and LP-PRP samples were immediately assayed and analyzed to measure protein concentrations. RESULTS BMC had a significantly higher interleukin 1 receptor antagonist (IL-1Ra) concentration than all other preparations (all P < .0009). LR-PRP also had a significantly higher IL-1Ra concentration than LP-PRP (P = .0006). There were no significant differences in IL-1Ra concentration based on age, sex, body mass index, or chronicity of injury in all preparations. LR-PRP had significantly higher concentrations of platelet-derived growth factor AA (PDGF-AA) and PDGF-AB/BB than all other preparations (all P < .0006). LR-PRP also had significantly higher concentrations of matrix metalloproteinase 1 (MMP-1) and soluble CD40 ligand than all other preparations (all P < .004). LP-PRP had significantly higher concentrations of MMPs, namely MMP-2, MMP-3, and MMP-12, than all other preparations (all P < .007). CONCLUSION BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic source for augmented healing in the postsurgical inflammatory and healing phases, owing to its significantly higher concentration of IL-1Ra as compared with LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues, including muscle and tendon, LR-PRP may be optimal given its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and soluble CD40 ligand.
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Affiliation(s)
| | | | | | | | | | | | - Grant J Dornan
- Steadman Philippon Research Institute, Vail, Colorado, USA
| | | | - Johnny Huard
- Steadman Philippon Research Institute, Vail, Colorado, USA
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Darrow M, Shaw B, Schmidt N, Boeger G, Budgett S. Treatment of shoulder osteoarthritis and rotator cuff tears with bone marrow concentrate and whole bone marrow injections. COGENT MEDICINE 2019. [DOI: 10.1080/2331205x.2019.1628883] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Affiliation(s)
- Marc Darrow
- Clinical Research, Darrow Stem Cell Institute, 11645 Wilshire Blvd Suite 120, Los Angeles, CA 90025, USA
| | - Brent Shaw
- Clinical Research, Darrow Stem Cell Institute, 11645 Wilshire Blvd Suite 120, Los Angeles, CA 90025, USA
| | - Nicholas Schmidt
- Clinical Research, Darrow Stem Cell Institute, 11645 Wilshire Blvd Suite 120, Los Angeles, CA 90025, USA
| | - Gabrielle Boeger
- Clinical Research, Darrow Stem Cell Institute, 11645 Wilshire Blvd Suite 120, Los Angeles, CA 90025, USA
| | - Saskia Budgett
- Clinical Research, Darrow Stem Cell Institute, 11645 Wilshire Blvd Suite 120, Los Angeles, CA 90025, USA
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Rivera E, Seijas R, Rubio M, García-Balletbó M, Vilar JM, Boada PL, Cugat R. Outcomes at 2-Years Follow-Up After Hip Arthroscopy Combining Bone Marrow Concentrate. J INVEST SURG 2019; 33:655-663. [DOI: 10.1080/08941939.2018.1535010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Eila Rivera
- Department of Orthopaedic Surgery, Hospital Quirónsalud, Barcelona, Spain
- Garcia-Cugat Fundation, Barcelona, Spain
- Department of Orthopaedic Surgery, Artroscopia GC, Barcelona, Spain
| | - Roberto Seijas
- Department of Orthopaedic Surgery, Hospital Quirónsalud, Barcelona, Spain
- Garcia-Cugat Fundation, Barcelona, Spain
- Department of Orthopaedic Surgery, Artroscopia GC, Barcelona, Spain
- Department of Anatomy, Universidad Internacional de Catalunya, Barcelona, Spain
| | - Mónica Rubio
- Garcia-Cugat Fundation, Barcelona, Spain
- Department of Animal Medicine and Surgery, Universidad CEU Cardenal Herrera, Moncada, Valencia, Spain
- CEU-UCH Chair of Medicine and Regenerative Surgery, Universidad CEU Cardenal Herrera, Moncada, Valencia, Spain
| | - Montserrat García-Balletbó
- Department of Orthopaedic Surgery, Hospital Quirónsalud, Barcelona, Spain
- Garcia-Cugat Fundation, Barcelona, Spain
- Department of Orthopaedic Surgery, Artroscopia GC, Barcelona, Spain
| | - Jose Manuel Vilar
- Research Institute in Biomedical and Health Sciences, Universidad de las Palmas de Gran Canaria, Las Palmas, Spain
| | - Patricia Laiz Boada
- Department of Orthopaedic Surgery, Hospital Quirónsalud, Barcelona, Spain
- Garcia-Cugat Fundation, Barcelona, Spain
- Department of Orthopaedic Surgery, Artroscopia GC, Barcelona, Spain
| | - Ramón Cugat
- Department of Orthopaedic Surgery, Hospital Quirónsalud, Barcelona, Spain
- Garcia-Cugat Fundation, Barcelona, Spain
- Department of Orthopaedic Surgery, Artroscopia GC, Barcelona, Spain
- CEU-UCH Chair of Medicine and Regenerative Surgery, Universidad CEU Cardenal Herrera, Moncada, Valencia, Spain
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Darrow M, Shaw B, Darrow B, Wisz S. Short-Term Outcomes of Treatment of Hip Osteoarthritis With 4 Bone Marrow Concentrate Injections: A Case Series. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2018; 11:1179547618791574. [PMID: 30116104 PMCID: PMC6088468 DOI: 10.1177/1179547618791574] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 07/06/2018] [Indexed: 12/27/2022]
Abstract
The use of mesenchymal stem cells from bone marrow concentrate (BMC) has become an increasingly popular option as an alternative to total joint replacement. Although there is evidence to support the use of BMC injections to improve quality of life for patients with knee osteoarthritis (OA), there is limited evidence to support its use in patients with hip OA. This case series provides the short-term outcomes of 4 hip OA patients who each underwent 4 BMC injections. On average, the last follow-up was administered 3.5 months after the first injection. The results show that patients experienced decreased resting and active pain compared with baseline and mean 72.4% total overall improvement. Patients also reported less difficulty in performing daily activities following the procedure. These encouraging results warrant further research to better understand the effects of BMC injections on hip OA.
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Affiliation(s)
- Marc Darrow
- Darrow Stem Cell Institute, Los Angeles, CA, USA
| | - Brent Shaw
- Darrow Stem Cell Institute, Los Angeles, CA, USA
| | | | - Stevie Wisz
- Darrow Stem Cell Institute, Los Angeles, CA, USA
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Shaw B, Darrow M, Derian A. Short-Term Outcomes in Treatment of Knee Osteoarthritis With 4 Bone Marrow Concentrate Injections. CLINICAL MEDICINE INSIGHTS-ARTHRITIS AND MUSCULOSKELETAL DISORDERS 2018; 11:1179544118781080. [PMID: 29977117 PMCID: PMC6024328 DOI: 10.1177/1179544118781080] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 05/06/2018] [Indexed: 12/27/2022]
Abstract
Background Preliminary research suggests that bone marrow concentrate (BMC), which contains mesenchymal stem cells and platelets, is a promising treatment for knee osteoarthritis. The aim of this study was to build on this preliminary research by reporting the short-term progress of 15 patients (20 knees) with knee osteoarthritis through 4 BMC treatments. Methods Patients underwent four sequential BMC treatments with mean injection times of 13.80 days after the first treatment, 21.40 days after the second treatment, and 33.50 days after the third treatment. The last follow-up was conducted a mean 86 days after the first treatment. Baseline and posttreatment outcomes of resting pain, active pain, lower functionality scale, and overall improvement percentage were compared after each treatment. Results Patients experienced statistically significant improvements in active pain and functionality score after the first treatment. Additionally, patients experienced a mean decrease in resting pain after the first treatment, yet outcomes were not statistically significant until after the second treatment. On average, patients experienced an 84.31% decrease in resting pain, a 61.95% decrease in active pain, and a 55.68% increase in functionality score at the final follow-up. Patients also reported a mean 67% total overall improvement at study conclusion. Outcomes at the final follow-up after the fourth treatment were statistically significant compared to outcomes at baseline, after first treatment, after second treatment, and after third treatment. Conclusions These results are promising, and additional research with a larger sample size and longer follow-up is needed to further examine the treatment effectiveness of multiple BMC injections for knee osteoarthritis.
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Affiliation(s)
- Brent Shaw
- Darrow Stem Cell Institute, Los Angeles, CA, USA
| | - Marc Darrow
- Darrow Stem Cell Institute, Los Angeles, CA, USA
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Early Clinical Outcomes of Intra-Articular Injections of Bone Marrow Aspirate Concentrate for the Treatment of Early Osteoarthritis of the Hip and Knee: A Cohort Study. PM R 2018; 10:1353-1359. [PMID: 29857166 DOI: 10.1016/j.pmrj.2018.05.016] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 04/21/2018] [Accepted: 05/13/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Bone marrow aspirate concentrate (BMC) is one of the few cell-based therapies available as a possible biological treatment for early osteoarthritis (OA). Its efficacy, safety, and benefit compared with other treatments are still to be determined. OBJECTIVE To assess the clinical outcomes of patients undergoing intra-articular injection of BMC for the treatment of early knee and hip OA. DESIGN Prospective, cohort study. SETTING Single institution, quaternary level of care. PATIENTS Nineteen patients (16 female and 3 male), totaling 25 joints (10 knees, 15 hips), treated with intra-articular BMC for early OA between 2014 and 2016. The mean age at time of the procedure was 58 ± 12.7 years (range, 30-80 years). The mean follow-up was 13.2 ± 6.3 months (range, 6-24 months). Inclusion criteria included ≥18 years; knee OA, Kellgren-Lawrence grade I-II; hip OA, Tönnis grade I-II; first-time intra-articular BMC therapy, after unsuccessful symptomatic and conservative treatments (ie, physical therapy, analgesics and anti-inflammatory drugs) for 6 months. Exclusion criteria included pregnancy; malignancy; rheumatologic diseases; infection; Kellgren-Lawrence grade III-IV; Tönnis grade III; and previous intra-articular injections or surgery. INTERVENTIONS All patients had autologous bone marrow aspirate harvested from the iliac crest and centrifuged to achieve BMC, for intra-articular injection. MAIN OUTCOME MEASUREMENTS The hypothesis was formulated before the study. Patient-reported outcomes measures were assessed preoperatively and at last follow-up using the Western Ontario and McMaster Universities Arthritis Index. RESULTS Western Ontario and McMaster Universities Arthritis Index improved from a baseline of 40.8 ± 18.3% to 20.6 ± 17% (P < .001) at final follow-up. The satisfaction rate was 63.2%. The minimal clinically important difference threshold of 9.15 points was reached by 64% of the patients. Two patients were converted to total hip arthroplasty at 8 months after BMC injection. CONCLUSIONS Intra-articular injections of BMC for the treatment of early knee or hip OA were safe and demonstrated satisfactory results in 63.2% of patients. Future studies are necessary to determine the efficacy of this technique and its safety profile. LEVEL OF EVIDENCE II.
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Biological Treatment for Osteoarthritis of the Knee: Moving from Bench to Bedside-Current Practical Concepts. Arthroscopy 2018; 34:1719-1729. [PMID: 29628381 DOI: 10.1016/j.arthro.2018.01.048] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 01/08/2018] [Accepted: 01/26/2018] [Indexed: 02/02/2023]
Abstract
Biological-based therapies for cartilage pathology have gained considerable recognition in the last few decades due to their potential benefits including their minimal invasiveness, capacity for unprecedented healing, and potential for rapid recovery. Consequently, these therapies are likely to have the most noteworthy impact on patients with degenerative joint changes who want to remain active. Currently, the most researched treatments include platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and cell-based therapies. Although further basic science research and well-designed randomized clinical trials are needed to elucidate the long-term role of these therapies in the treatment of osteoarthritis, there is compelling evidence for their use for certain indications. This article aims to review the existing literature for biological-based treatment options for osteoarthritis, critically assessing the current evidence-based recommendations and identify potential avenues for development.
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El-Jawhari JJ, Brockett CL, Ktistakis I, Jones E, Giannoudis PV. The regenerative therapies of the ankle degeneration: a focus on multipotential mesenchymal stromal cells. Regen Med 2018; 13:175-188. [PMID: 29553890 DOI: 10.2217/rme-2017-0104] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The ankle degeneration ranging from focal osteochondral lesions to osteoarthritis can cause a total joint function loss. With rising life expectancy and activity of the patients, various regenerative therapies were introduced aiming to preserve the joint function via the induction of cartilage and bone repair. Here, biological events and mechanical changes of the ankle degeneration were discussed. The regenerative therapies were reviewed versus the standard surgical treatment. We especially focused on the use of mesenchymal (multipotential) stromal cells (MSCs) highlighting their dual functions of regeneration and cell modulation with an emphasis on the emerging MSC-based clinical studies. Being at an early step, more basic and clinical research is needed to optimize the applications of all ankle regenerative therapies including MSC-based methods.
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Affiliation(s)
- Jehan J El-Jawhari
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Clinical pathology department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Claire L Brockett
- Institute of Medical & Biological Engineering, University of Leeds, Leeds, UK
| | - Ioannis Ktistakis
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Academic Unit of Trauma and Orthopaedic Surgery, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Elena Jones
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Peter V Giannoudis
- Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK
- Academic Unit of Trauma and Orthopaedic Surgery, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Hussain ZB, Chahla J, LaPrade RF, Mandelbaum BR. Orthobiologics: Today and Tomorrow. CARTILAGE RESTORATION 2018:131-142. [DOI: 10.1007/978-3-319-77152-6_11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Desando G, Bartolotti I, Cavallo C, Schiavinato A, Secchieri C, Kon E, Filardo G, Paro M, Grigolo B. Short-Term Homing of Hyaluronan-Primed Cells: Therapeutic Implications for Osteoarthritis Treatment. Tissue Eng Part C Methods 2017; 24:121-133. [PMID: 29108480 DOI: 10.1089/ten.tec.2017.0336] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The evaluation of key factors modulating cell homing following injection can provide new insights in the comprehension of unsolved biological questions about the use of cell therapies for osteoarthritis (OA). The main purpose of this in vivo study was to investigate the biodistribution of an intra-articular injection of mesenchymal stromal cells (MSCs) and bone marrow concentrate (BMC) in a rabbit OA model and whether the additional use of sodium hyaluronate (HA) could modulate their migration and delay joint degeneration. OA was surgically induced in adult male New Zealand rabbits. A group of animals was used to test the biodistribution of labeled cells alone or with HA at 7 and 14 days to investigate cell migration. The efficacy of treatments was evaluated in other experimental groups at 2 months. Histology and immunohistochemistry for markers identifying anabolic and catabolic processes in the cartilage and meniscus, or macrophage subset population in the synovial membrane, were performed. Kruskal-Wallis test, followed by post hoc Dunn's test, and Spearman's rank-order correlation method were used. MSCs and BMC preferentially migrate toward tissue areas showing OA features in the meniscus and cartilage and in detail near inflammatory zones in the synovial membrane. The combination with HA contributed to boost cell migration toward articular cartilage. In general, both labeled cells combined with HA were found near cell cluster and fissures in the cartilage and meniscus, respectively, and close to areas of synovial membrane showing mainly anti-inflammatory macrophages. A promotion of joint repair was observed at different levels for all treatments, although BMC-HA treatment resulted as the best strategy to support joint repair. This last, displayed a good protein expression of type II collagen in the cartilage, as well as the presence of anti-inflammatory macrophages in the synovial membrane at 2 months from the treatment. Studies tracking cell biodistribution indicate that priming progenitor cells with HA modulated cell homing favoring not only attachment but also their integration within articular cartilage.
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Affiliation(s)
- Giovanna Desando
- 1 Laboratorio RAMSES, Istituto Ortopedico Rizzoli (IOR) , Bologna, Italy
| | | | - Carola Cavallo
- 1 Laboratorio RAMSES, Istituto Ortopedico Rizzoli (IOR) , Bologna, Italy
| | | | | | - Elizaveta Kon
- 3 Humanitas University Department of Biomedical Sciences , Humanitas Clinical and Research Center, Milan, Italy
| | - Giuseppe Filardo
- 4 Laboratorio di Nano-Biotecnologie, Istituto Ortopedico Rizzoli , Bologna, Italy
| | | | - Brunella Grigolo
- 6 Laboratorio RAMSES/Immunoreumatologia e Rigenerazione Tissutale, IOR , Bologna, Italy
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Moatshe G, Morris ER, Cinque ME, Pascual-Garrido C, Chahla J, Engebretsen L, Laprade RF. Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates. Acta Orthop 2017; 88:670-674. [PMID: 28831830 PMCID: PMC5694813 DOI: 10.1080/17453674.2017.1368899] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
- Knee pathologies including focal cartilage injuries, osteoarthritis (OA), and ligament injuries are common. The poor regeneration and healing potential of cartilage has led to the search for other treatment modalities with improved healing capacity. Furthermore, with an increasing elderly population that desires to remain active, the burden of knee pathologies is expected to increase. Increased sports participation and the desire to return to activities faster is also demanding more effective and minimally invasive treatment options. Thus, the use of biologic agents in the treatment of knee pathologies has emerged as a potential option. Despite the increasing use of biologic agents for knee pathology, there are conflicting results on the efficacy of these products. Furthermore, strong data supporting the optimal preparation methods and composition for widely used biologic agents, such as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), largely remain absent from the literature. This review presents the literature on the most commonly employed biologic agents for the different knee pathologies.
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Affiliation(s)
- Gilbert Moatshe
- Oslo University Hospital and University of Oslo, Oslo, Norway,Steadman Philippon Research Institute, Vail, CO, USA,OSTRC, The Norwegian School of Sports Sciences, Oslo, Norway
| | | | - Mark E Cinque
- Steadman Philippon Research Institute, Vail, CO, USA
| | | | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, CO, USA
| | - Lars Engebretsen
- Oslo University Hospital and University of Oslo, Oslo, Norway,OSTRC, The Norwegian School of Sports Sciences, Oslo, Norway
| | - Robert F Laprade
- Steadman Philippon Research Institute, Vail, CO, USA,Steadman Clinic, Vail, CO, USA,Correspondence:
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Abstract
BACKGROUND Cell and growth factor based strategies bear great potential to support the healing processes in cartilage repair and the therapy of osteoarthritic joints. OBJECTIVES The following review provides an overview of novel experimental strategies for the therapy of focal cartilage defects and osteoarthritis, with emphasis on cell and growth factor based approaches. MATERIALS AND METHODS The authors summarize their own data regarding the intraarticular injection of stem cells to treat osteoarthritis of the knee and provide a synopsis of the available literature discussing the most significant publications. RESULTS The development of novel strategies for the treatment of focal and arthrotic cartilage lesions focuses on the application of growth factors, platelet rich plasma (PRP), bone marrow (BMSAC) or adipose derived (stromal vascular fraction - SVF) cell concentrates, and ex vivo expanded mesenchymal stem cells (MSC). First clinical data on the use of expanded MSCs show the potential of this innovative therapeutic strategy. These approaches, however, are governed by EU law and often require approval by regulatory bodies. CONCLUSION Currently, only a limited number of published, randomized, controlled trials available. Therefore, it is not possible to finally assess the efficacy of these strategies at this point in time.
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Ramkumar PN, Navarro SM, Haeberle HS, Chughtai M, Demetriades C, Piuzzi NS, Mont MA, Bauer TW, Muschler GF. Cellular therapy injections in today's orthopedic market: A social media analysis. Cytotherapy 2017; 19:1392-1399. [PMID: 28916228 DOI: 10.1016/j.jcyt.2017.08.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 08/02/2017] [Accepted: 08/09/2017] [Indexed: 01/11/2023]
Abstract
BACKGROUND The current state of cellular therapy for musculoskeletal conditions is at a crossroads. Marketing efforts are often outpacing clinical evidence and regulatory control. QUESTIONS/PURPOSES This study was an effort to describe the marketing of cellular therapy in musculoskeletal medicine by evaluating the content in popular social media channels. Specifically, media posts were evaluated for the following: (1) perspective, (2) tone, (3) content and (4) visibility. PATIENT AND METHODS Social media content related to cell therapy for musculoskeletal conditions was assessed in a search using 28 hashtags on the public domains of Instagram and Twitter over a 2-year period (2014-2016) that resulted in analysis of 698 posts. Supplemental analyses of LinkedIn and Facebook domains were also conducted. A categorical scoring system was used to analyze perspective (patient, family or friend, business or organization), tone (positive, negative), content (education, advertisement, research, media coverage or patient experience) and visibility (number of hashtags per post). Sub-analyses of the advertisement content from various perspectives (patients, physicians and businesses) were performed. RESULTS The media perspective was most frequently from a business or organization (83%; n = 575). A total of 94% of the posts had a positive tone and only 6% had a negative tone, and the only negative posts came from patients (60% positive and 40% negative). The most common content of social media posts were advertisements, representing 68% (n = 477) of all posts; this was confirmed in the Facebook analysis. The mean number of hashtags was five per post. Sub-analyses revealed approximately half of the advertising posts originated from a single business that recruited physicians to market their cell-based therapies on social media, which was confirmed in the LinkedIn analysis. CONCLUSION The market messages related to cell-based therapies for musculoskeletal conditions available on social media are dominated by businesses that seem to use a network of physicians, apply several hashtags to enhance visibility and advertise these largely unproven modalities. The posts portray an almost exclusively positive tone, without providing a "fair balance" on the risks, benefits and limitations.
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Affiliation(s)
- Prem N Ramkumar
- Cleveland Clinic, Department of Orthopedic Surgery, Cleveland, Ohio, USA.
| | - Sergio M Navarro
- Baylor College of Medicine, Department of Orthopaedic Surgery, Houston, Texas, USA
| | - Heather S Haeberle
- Baylor College of Medicine, Department of Orthopaedic Surgery, Houston, Texas, USA
| | - Morad Chughtai
- Cleveland Clinic, Department of Orthopedic Surgery, Cleveland, Ohio, USA
| | | | - Nicolas S Piuzzi
- Cleveland Clinic, Department of Orthopedic Surgery, Cleveland, Ohio, USA
| | - Michael A Mont
- Cleveland Clinic, Department of Orthopedic Surgery, Cleveland, Ohio, USA
| | - Thomas W Bauer
- Cleveland Clinic, Department of Orthopedic Surgery, Cleveland, Ohio, USA
| | - George F Muschler
- Cleveland Clinic, Department of Orthopedic Surgery, Cleveland, Ohio, USA
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El-Jawhari JJ, Cuthbert R, McGonagle D, Jones E, Giannoudis PV. The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful Measurement of the Bone Marrow Quality for Cartilage and Bone Regenerative Therapy. J Bone Joint Surg Am 2017; 99:1305-1313. [PMID: 28763416 PMCID: PMC6125756 DOI: 10.2106/jbjs.16.01138] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Bone marrow aspirates and concentrates are increasingly being used for musculoskeletal regenerative therapies, providing bone and cartilage progenitors. However, the quality of these bone marrow samples remains imprecise within clinical settings. As there is a need for the development of these therapies, a method of counting CD45CD271 cells was optimized and tested as an indicator of bone marrow sample quality. METHODS Bone marrow aspirates were collected from 54 donors (28 male and 26 female; median age of 48 years). The reagent concentrations were optimized for fast staining, and an acoustic-focusing flow cytometer (Attune) was used to enable automated CD45CD271 cell counting in bone marrow aspirates, bone marrow concentrates, and samples loaded onto a collagen scaffold. The CD45CD271 cell counts were compared with those obtained using another flow-cytometry-based method (LSR II) and with connective tissue progenitor (CTP) counts quantified using a colony forming unit-fibroblast (CFU-F) assay. RESULTS The optimized method enabled the counting of CD45CD271 cells within only 15 minutes. The quantified cell counts (median, 1,520; range, 96 to 20,992 cells/mL of bone marrow) were positively correlated with the CTP counts (p < 0.0001; r = 0.7237). In agreement with CFU-F and LSR II-based assays, the CD45CD271 cell counts quantified using the Attune-based method decreased with age in the samples from female but not male donors (p = 0.0015 and p = 0.3877, respectively). A significant increase in CD45CD271 cell counts was detected following bone marrow concentration (mean, 5-fold; 95% confidence interval [CI], 3.6 to 7.2-fold). Additionally, the number of CD45CD271 cells attached to the collagen scaffold was positively correlated with the number of progenitor cells that survived on the scaffold after 2-week culture (p = 0.0348). CONCLUSIONS An assay for counting CD45CD271 cells may provide a useful measurement of bone marrow quality. While the specificity of this measurement of CD45CD271 cells remained low in our experimental conditions, CD45CD271 cell counts were positively and modestly correlated with the prevalence of CTPs. CLINICAL RELEVANCE A fast and automated assessment of bone marrow aspirate/concentrate quality using CD45CD271 cell counting may be a useful tool for improving the quality of regenerative therapy.
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Affiliation(s)
- Jehan J. El-Jawhari
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, Leeds, United Kingdom,NIHR-Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Chapel Allerton Hospital, University of Leeds, Leeds, United Kingdom,Clinical Pathology Department, Mansoura University, Mansoura, Egypt
| | - Richard Cuthbert
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, Leeds, United Kingdom,NIHR-Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Chapel Allerton Hospital, University of Leeds, Leeds, United Kingdom
| | - Dennis McGonagle
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, Leeds, United Kingdom,NIHR-Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Chapel Allerton Hospital, University of Leeds, Leeds, United Kingdom
| | - Elena Jones
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, Leeds, United Kingdom,NIHR-Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Chapel Allerton Hospital, University of Leeds, Leeds, United Kingdom
| | - Peter V. Giannoudis
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, Leeds, United Kingdom,NIHR-Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Chapel Allerton Hospital, University of Leeds, Leeds, United Kingdom,E-mail address for P.V. Giannoudis:
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Garay-Mendoza D, Villarreal-Martínez L, Garza-Bedolla A, Pérez-Garza DM, Acosta-Olivo C, Vilchez-Cavazos F, Diaz-Hutchinson C, Gómez-Almaguer D, Jaime-Pérez JC, Mancías-Guerra C. The effect of intra-articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis. Int J Rheum Dis 2017; 21:140-147. [PMID: 28752679 DOI: 10.1111/1756-185x.13139] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM Management of osteoarthritis (OA) is basically symptomatic. Recently, stem cells (SC) have been used in the search for an optimum treatment. We decided to conduct a controlled clinical trial to determine if a single intra-articular injection of in vivo stimulated bone marrow SC could lead to an improvement in pain management and quality of life in patients with knee OA. METHOD This was a prospective, open-label, phase I/II clinical trial to assess the safety and efficacy of a single intra-articular injection of autologous stimulated bone marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders older than 30 years with confirmed diagnosis of OA who signed informed consent were included in two groups: SC group received in vivo BM stimulation with subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC were obtained by BM aspiration and administered in a single intra-articular injection. The control group received exclusively oral acetaminophen. Visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were performed at 1 week, 1 month and 6 months in both groups. This trial was registered in ClinialTrials.gov NCT01485198. RESULTS A total of 61 patients were included. Socio-demographic characteristics, OA grades and initial scores were similar in both groups. The BM-SC group showed significant improvement in knee pain and quality of life during the 6-month follow-up. CONCLUSION The study demonstrates feasibility and supports efficacy of a completely ambulatory procedure in treatment of knee OA.
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Affiliation(s)
- Domingo Garay-Mendoza
- Traumatology and Orthopaedics Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Laura Villarreal-Martínez
- Hematology Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Alejandra Garza-Bedolla
- Hematology Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Daniela M Pérez-Garza
- Hematology Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Carlos Acosta-Olivo
- Traumatology and Orthopaedics Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Felix Vilchez-Cavazos
- Traumatology and Orthopaedics Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Cesar Diaz-Hutchinson
- Traumatology and Orthopaedics Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - David Gómez-Almaguer
- Hematology Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - José C Jaime-Pérez
- Hematology Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
| | - Consuelo Mancías-Guerra
- Hematology Service, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México
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Bone Marrow Aspirate Concentrate Harvesting and Processing Technique. Arthrosc Tech 2017; 6:e441-e445. [PMID: 28580265 PMCID: PMC5443590 DOI: 10.1016/j.eats.2016.10.024] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2016] [Accepted: 10/24/2016] [Indexed: 02/03/2023] Open
Abstract
Bone marrow obtained by iliac crest aspiration is a common source for harvesting mesenchymal stem cells, other progenitor cells, and associated cytokine/growth factors. Recent studies have reported good to excellent outcomes with the use of bone marrow aspirate concentrate (BMAC) for pain relief in the treatment of focal chondral lesions and osteoarthritis of the knee. However, the harvesting and processing technique are crucial to achieve satisfactory results. Several studies have examined outcomes after BMAC injection, with encouraging results, but there is a lack of consensus in terms of the frequency of injection, the amount of BMAC that is injected, and the timing of BMAC injections. The purpose of this Technical Note was to describe a standardized bone marrow aspiration harvesting technique and processing method.
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45
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Kraeutler MJ, Chahla J, LaPrade RF, Pascual-Garrido C. Biologic Options for Articular Cartilage Wear (Platelet-Rich Plasma, Stem Cells, Bone Marrow Aspirate Concentrate). Clin Sports Med 2017; 36:457-468. [PMID: 28577706 DOI: 10.1016/j.csm.2017.02.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Biological treatments for articular cartilage repair have gained in popularity in the past decade. Advantages of these therapies include minimal invasiveness, improved healing time, and faster recovery. Biological therapies for cartilage repair include platelet-rich plasma, bone marrow aspirate concentrate, and cell-based therapies. These methods have the added benefit of containing growth factors and/or stem cells that aid in recovery and regeneration. The purpose of this article is to review the current cartilage treatment options and the existing literature on outcomes, complications, and safety profile of these products for use in the knee and hip joints.
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Affiliation(s)
- Matthew J Kraeutler
- Department of Orthopedics, University of Colorado School of Medicine, 1635 Aurora Ct, Aurora, CO 80045, USA
| | - Jorge Chahla
- Steadman Philippon Research Institute, 181 West Meadow Drive, Suite 400, Vail, CO 81657, USA
| | - Robert F LaPrade
- Steadman Philippon Research Institute, 181 West Meadow Drive, Suite 400, Vail, CO 81657, USA
| | - Cecilia Pascual-Garrido
- Department of Orthopedics, Washington University, 660 South Euclid Avenue, Campus Box 8233, St Louis, MO 63110, USA.
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46
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Atesok K, Fu FH, Sekiya I, Stolzing A, Ochi M, Rodeo SA. Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential. Knee Surg Sports Traumatol Arthrosc 2017; 25:626-636. [PMID: 26298714 DOI: 10.1007/s00167-015-3763-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Accepted: 08/13/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE The purpose of this study was to summarize the current evidence on the use of stem cells in the elderly population with degenerative orthopaedic pathologies and to highlight the pathophysiologic mechanisms behind today's therapeutic challenges in stem cell-based regeneration of destructed tissues in the elderly patients with osteoarthritis (OA), degenerative disc disease (DDD), and tendinopathies. METHODS Clinical and basic science studies that report the use of stem cells in the elderly patients with OA, DDD, and tendinopathies were identified using a PubMed search. The studies published in English have been assessed, and the best and most recent evidence was included in the current study. RESULTS Evidence suggests that, although short-term results regarding the effects of stem cell therapy in degenerative orthopaedic pathologies can be promising, stem cell therapies do not appear to reverse age-related tissue degeneration. Causes of suboptimal outcomes can be attributed to the decrease in the therapeutic potential of aged stem cell populations and the regenerative capacity of these cells, which might be negatively influenced in an aged microenvironment within the degenerated tissues of elderly patients with OA, DDD, and tendinopathies. CONCLUSIONS Clinical protocols guiding the use of stem cells in the elderly patient population are still under development, and high-level randomized controlled trials with long-term outcomes are lacking. Understanding the consequences of age-related changes in stem cell function and responsiveness of the in vivo microenvironment to stem cells is critical when designing cell-based therapies for elderly patients with degenerative orthopaedic pathologies.
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Affiliation(s)
- Kivanc Atesok
- Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 3471 Fifth Avenue, Suite 1011, Pittsburgh, PA, 15213, USA.
| | - Freddie H Fu
- Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 3471 Fifth Avenue, Suite 1011, Pittsburgh, PA, 15213, USA
| | - Ichiro Sekiya
- Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan
| | - Alexandra Stolzing
- Center for Biological Engineering, Wolfson School, Loughborough University, Loughborough, UK.,Translational Center for Regenerative Medicine (TRM), University Leipzig, Leipzig, Germany
| | - Mitsuo Ochi
- Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Scott A Rodeo
- Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, NY, USA
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El Abd O, Amadera JED, Pimentel DC, Bhargava A. Nonsurgical Treatment (Indications, Limitations, Outcomes): Injections. HIP JOINT RESTORATION 2017:299-314. [DOI: 10.1007/978-1-4614-0694-5_28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Castagnini F, Pellegrini C, Perazzo L, Vannini F, Buda R. Joint sparing treatments in early ankle osteoarthritis: current procedures and future perspectives. J Exp Orthop 2016; 3:3. [PMID: 26915003 PMCID: PMC4713405 DOI: 10.1186/s40634-016-0038-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Accepted: 01/08/2016] [Indexed: 02/07/2023] Open
Abstract
Ankle osteoarthritis (AOA) is a severe pathology, mostly affecting a post-traumatic young population. Arthroscopic debridement, arthrodiastasis, osteotomy are the current joint sparing procedures, but, in the available studies, controversial results were achieved, with better outcomes in case of limited degeneration. Only osteotomy in case of malalignment is universally accepted as a joint sparing procedure in case of partial AOA. Recently, the biological mechanism of osteoarthritis has been intensively studied: it is a whole joint pathology, affecting cartilage, bone and synovial membrane. In particular, the first stage is characterized by a reversible catabolic activity with a state of chondropenia. Thus, biological procedures for early AOA were proposed in order to delay or to avoid end stage procedures. Mesenchymal stem cells (MSCs) may be a good solution to prevent or reverse degeneration, due to their immunomodulatory features (able to control the catabolic joint environment) and their regenerative osteochondral capabilities (able to treat the chondral defects). In fact, MSCs may regulate the cytokine cascade and the metalloproteinases release, restoring the osteochondral tissue as well. After interesting reports of mesenchymal stem cells seeded on scaffold and applied to cartilage defects in non-degenerated joints, bone marrow derived cells transplantation appears to be a promising technique in order to control the degenerative pathway and restore the osteochondral defects.
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Affiliation(s)
- Francesco Castagnini
- I Clinic of Orthopaedics and Traumatology, Rizzoli Orthopaedic Institute, Bologna, Italy.
| | - Camilla Pellegrini
- I Clinic of Orthopaedics and Traumatology, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Luca Perazzo
- I Clinic of Orthopaedics and Traumatology, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Francesca Vannini
- I Clinic of Orthopaedics and Traumatology, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Roberto Buda
- Orthopaedics and Traumatology, I Clinic, Rizzoli Orthopaedic Institute, University of Bologna, Bologna, Italy
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Cui GH, Wang YY, Li CJ, Shi CH, Wang WS. Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis. Exp Ther Med 2016; 12:3390-3400. [PMID: 27882169 DOI: 10.3892/etm.2016.3791] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 08/16/2016] [Indexed: 01/10/2023] Open
Abstract
To assess the clinical efficacy and safety of mesenchymal stem cell (MSC) treatment for osteoarthritis of the knee (KOA), a systematic electronic literature search was performed on PubMed, EMBASE and Web of Science. Studies published in English from the earliest record to December 2014 were searched using the following keywords: Cartilage defect, cartilage repair, osteoarthritis, KOA, stem cells, MSCs, bone marrow concentrate (BMC), adipose-derived mesenchymal stem cells, synovial-derived mesenchymal stem cells and peripheral blood-derived mesenchymal stem cells. The effect sizes of selected studies were determined by extracting pain scores from the visual analog scale and functional changes from International Knee Documentation Committee and Lysholm and Western Ontario and McMaster Universities Osteoarthritis Index before and after MSCs or reference treatments at 3, 6, 12, and 24 months. The factors were analyzed and the outcomes were modified after comparing the MSC group pooled values with the pretreatment baseline or between different treatment arms. A systematic search identified 18 clinical trials on this topic, including 10 single-arm prospective studies, four quasi-experimental studies and four randomized controlled trials that used BMCs to treat 565 patients with KOA in total. MSC treatment in patients with KOA showed continual efficacy for 24 months compared with their pretreatment condition. Effectiveness of MSCs was improved at 12 and 24 months post-treatment, compared with at 3 and 6 months. No dose-responsive association in the MSCs numbers was demonstrated. However, patients with arthroscopic debridement, activation agent or lower degrees of Kellgren-Lawrence grade achieved improved outcomes. MSC application ameliorated the overall outcomes of patients with KOA, including pain relief and functional improvement from basal evaluations, particularly at 12 and 24 months after follow-up.
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Affiliation(s)
- Gang-Hua Cui
- Department of Orthopedics, Medical College of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
| | - Yang Yang Wang
- Department of Orthopedics, Medical College of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
| | - Chang-Jun Li
- Department of Orthopedics, Medical College of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
| | - Chen-Hui Shi
- Department of Orthopedics, Medical College of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
| | - Wei-Shan Wang
- Department of Orthopedics, Medical College of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
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50
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Chahla J, Piuzzi NS, Mitchell JJ, Dean CS, Pascual-Garrido C, LaPrade RF, Muschler GF. Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis. J Bone Joint Surg Am 2016; 98:1511-21. [PMID: 27655978 DOI: 10.2106/jbjs.15.01495] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported. METHODS We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score. RESULTS Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82). CONCLUSIONS The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Jorge Chahla
- Steadman Philippon Research lnstitute, Vail, Colorado
| | - Nicolas S Piuzzi
- Institute of Orthopedics, "Carlos E. Ottolenghi" Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | | | - Chase S Dean
- Steadman Philippon Research lnstitute, Vail, Colorado
| | | | - Robert F LaPrade
- Steadman Philippon Research lnstitute, Vail, Colorado The Steadman Clinic, Vail, Colorado
| | - George F Muschler
- Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
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