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Sharma V, Sakhalkar U, Nadkarni P, Mishal R, Parandhaman D, Vichare K, Francis A, Khanna M, Kukreja M, Sharma A. Cytoprotective Effect of Growth Factors Derived From Platelets on Corticosteroid-Treated Primary Anterior Cruciate Ligament-Derived Stromal Cells and Chondrocytes. Cureus 2024; 16:e65566. [PMID: 39192919 PMCID: PMC11348450 DOI: 10.7759/cureus.65566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2024] [Indexed: 08/29/2024] Open
Abstract
Background The use of corticosteroids, such as methylprednisolone, for pain management is a common clinical practice. However, it is well known that corticosteroids induce toxicity in anterior cruciate ligament (ACL)-derived stromal cells and chondrocytes. Growth factors from platelets have anti-inflammatory effects that can potentially limit the cytotoxic effects of corticosteroids. In this study, we explored the role of growth factors obtained from the OssinextTM kit (commercially available Wockhardt growth factor concentrate (GFC) kit) in recovering methylprednisolone-induced cell damage. Methodology Primary ACL-derived stromal cells and chondrocytes were isolated from human ligament tissue and articular cartilage, respectively, and characterized by immunophenotyping, gene expression analysis, and immunostaining. GFC obtained from OssinextTM kit was used for the experiments. The ACL-derived stromal cells and chondrocytes were treated with methylprednisolone, alone or in combination with GFC. Cell viability was measured by the neutral red uptake assay. Changes in cell morphology and collagen pattern were observed microscopically by H&E staining and immunostaining, respectively. Cell proliferation was assessed by cell migration assay, and the cell ultra-structure was analyzed using transmission electron microscopy. Results Methylprednisolone was found to induce cytotoxicity, altered cell morphology, reduced cell proliferation, and organelle damage in both ACL-derived stromal cells and chondrocytes. GFC obtained from the OssinextTM kit was able to restore cell viability and reverse the cell structure damages induced by methylprednisolone. GFC was found to recover and protect the cells, both when used in combination with steroids and when used after the steroid treatment. Conclusions The results indicate that GFC may be clinically beneficial when used in combination with steroids to mitigate their adverse effects.
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Affiliation(s)
- Vijay Sharma
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Ulka Sakhalkar
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Pratiksha Nadkarni
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Rashmi Mishal
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Dinesh Parandhaman
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Kirti Vichare
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Anjalina Francis
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
| | - Mudit Khanna
- Orthopaedic Surgery, Wockhardt Hospital, Mumbai, IND
| | - Mohit Kukreja
- Orthopaedic Surgery, Wockhardt Hospital, Mumbai, IND
| | - Anuka Sharma
- Department of Regenerative Medicine, Wockhardt Regenerative Pvt. Ltd., Mumbai, IND
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Lana JFSD, da Fonseca LF, Macedo RDR, Mosaner T, Murrell W, Kumar A, Purita J, de Andrade MAP. Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects. World J Stem Cells 2021; 13:155-167. [PMID: 33708344 PMCID: PMC7933989 DOI: 10.4252/wjsc.v13.i2.155] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/15/2020] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
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Affiliation(s)
| | | | - Rafael da Rocha Macedo
- Department of Orthopedics, Rede D’Or Unit IFOR Hospital, São Bernardo do Campo 09715-021, SP, Brazil
| | - Tomas Mosaner
- Department of Orthopedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil
| | - William Murrell
- Department of Orthopaedics, Healthpoint UAE, Abu Dhabi 00000, United Arab Emirates
| | - Ashok Kumar
- Department of Orthopaedics, My Doc Specialist Medical Centre, Dubai 00000, United Arab Emirates
| | - Joseph Purita
- Department of Orthopedics, Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
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Kunze KN, Hannon CP, Fialkoff JD, Frank RM, Cole BJ. Platelet-rich plasma for muscle injuries: A systematic review of the basic science literature. World J Orthop 2019; 10:278-291. [PMID: 31363458 PMCID: PMC6650633 DOI: 10.5312/wjo.v10.i7.278] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 05/10/2019] [Accepted: 06/25/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Platelet-rich plasma (PRP) is an increasingly used biologic adjunct for muscle injuries, as it is thought to expedite healing. Despite its widespread use, little is known regarding the mechanisms by which PRP produces its efficacious effects in some patients.
AIM To clarify the effects of PRP on muscular pathologies at the cellular and tissue levels by evaluating the basic science literature.
METHODS A systematic review of PubMed/MEDLINE and EMBASE databases was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist. Level III in vivo and in vitro studies examining PRP effects on muscles, myocytes and/or myoblasts were eligible for inclusion. Extracted data included PRP preparation methods and study results.
RESULTS Twenty-three studies were included (15 in vivo, 6 in vitro, 2 in vitro/in vivo). Only one reported a complete PRP cytology (platelets, and red and white blood cell counts). Five in vitro studies reported increased cellular proliferation, four reported increased gene expression, and three reported increased cellular differentiation. Five in vivo studies reported increased gene expression, three reported superior muscle regeneration, and seven reported improved histological quality of muscular tissue.
CONCLUSION The basic science literature on the use of PRP in muscle pathology demonstrates that PRP treatment confers several potentially beneficial effects on healing in comparison to controls. Future research is needed to determine optimal cytology, dosing, timing, and delivery methods of PRP for muscle pathologies.
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Affiliation(s)
- Kyle N Kunze
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, United States
| | - Charles P Hannon
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, United States
| | - Jared D Fialkoff
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, United States
| | - Rachel M Frank
- Department of Orthopedic Surgery, University of Colorado School of Medicine, Boulder, CO 80309, United States
| | - Brian J Cole
- Department of Orthopedics, Rush University Medical Center, Chicago, IL 60612, United States
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Centeno C, Markle J, Dodson E, Stemper I, Williams C, Hyzy M, Ichim T, Freeman M. Symptomatic anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow concentrate and platelet products: a non-controlled registry study. J Transl Med 2018; 16:246. [PMID: 30176875 PMCID: PMC6122476 DOI: 10.1186/s12967-018-1623-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Accepted: 08/29/2018] [Indexed: 12/13/2022] Open
Abstract
Background Bone marrow concentrate (BMC) has shown promise in the treatment of several orthopedic conditions. This registry study investigated the use of autologous BMC and platelet products for percutaneous anterior cruciate ligament (ACL) treatment. Methods Twenty-nine patients presenting to a single outpatient interventional musculoskeletal and pain practice with symptomatic grade 1, 2, or 3 ACL tears with less than 1 cm retraction were enrolled. Patients were treated with a percutaneous ACL injection of autologous BMC and platelet products using fluoroscopic guidance. Pre- and post-treatment magnetic resonance imaging analysis was completed for 23 patients using ImageJ software for an objective quantitative analysis of pixel density as a proxy for ACL integrity. Subjective clinical outcome measures collected pre-treatment and at 1, 3, 6, 12, 18, 24, and 36 months post-treatment include the Numerical Pain Scale (NPS), the Lower Extremity Functional Scale (LEFS), the International Knee Documentation Committee (IKDC) form, and a modified version of the Single Assessment Numeric Evaluation. Results Seventy-seven percent of patients treated with BMC injections into the ACL showed significant improvement (p < 0.01) in objective measures of ACL integrity at an average of 8.8 months (median 4.7 months). The mean of last patient-reported improvement was 72% (SD = 35) at an average of 23 (SD = 10) months post-treatment. Mean scores were found to be significantly different (p < 0.05) for the NPS at 6, 18, and 24 months, and LEFS and IKDC at all time points (i.e. 1, 3, 6, 12, 18, 24, and 36 months) relative to baseline. Conclusion In symptomatic patients with grade 1, 2, or even grade 3 tears with minimal retraction, ACL treatment with percutaneous injection of BMC and platelet products shows promise as a non-surgical alternative. However, a larger randomized controlled trial is warranted to confirm these findings. Trial registration NCT03011398. A Clinical Registry of Orthobiologics Procedures. https://clinicaltrials.gov/ct2/show/NCT03011398?term=orthobiologics&rank=1. Registered 29 December 2016. Enrollment 1 December 2011-retrospectively registered
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Affiliation(s)
- Christopher Centeno
- Centeno-Schultz Clinic, 403 Summit Blvd Suite 201, Broomfield, CO, 80021, USA.,Regenexx, LLC, Des Moines, IA, 50321, USA
| | - Jason Markle
- Centeno-Schultz Clinic, 403 Summit Blvd Suite 201, Broomfield, CO, 80021, USA
| | | | | | | | - Matthew Hyzy
- Centeno-Schultz Clinic, 403 Summit Blvd Suite 201, Broomfield, CO, 80021, USA
| | | | - Michael Freeman
- CAPHRI School of Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands
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Hussain N, Johal H, Bhandari M. An evidence-based evaluation on the use of platelet rich plasma in orthopedics - a review of the literature. SICOT J 2017; 3:57. [PMID: 28990574 PMCID: PMC5632954 DOI: 10.1051/sicotj/2017036] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 06/06/2017] [Indexed: 12/21/2022] Open
Abstract
Within orthopedics, the use of platelet-rich plasma (PRP) has been rapidly increasing in popularity, however, its true effectiveness has yet to be fully established. Several studies find that injecting PRP to the site of injury does not provide any significant benefit with respect to clinical outcomes; however, many others report the contrary. Due to the conflicting evidence and multiple meta-analyses conducted on the topic, a literature review of high-quality evidence on the use of PRP for common orthopaedic conditions was performed. Thus far, the evidence appears to suggest that PRP may provide some benefit in patients who present with knee osteoarthritis or lateral epicondylitis. On the other hand, evidence appears to be inconsistent or shows a minimal benefit for PRP usage in rotator cuff repair, patellar and Achilles tendinopathies, hamstring injuries, anterior cruciate ligament (ACL) repair, and medial epicondylitis. There is limited confidence in the conclusions from the published meta-analyses due to issues with statistical pooling, and limited subgroup analyses exploring the substantial heterogeneity across studies. Evidence-based clinicians considering the use of PRP in their patients with musculoskeletal injuries should be weary that the literature appears to be inconsistent and thus far, inconclusive.
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Affiliation(s)
- Nasir Hussain
- Central Michigan University College of Medicine, CMED Building, 1280 S. East Campus St., Mt. Pleasant, MI 48859, USA
| | - Herman Johal
- Division of Orthopaedic Surgery, Department of Surgery, McMaster University & Centre for Evidence Based Orthopaedics, 293 Wellington Street North, Suite 110, Hamilton, Ontario L8L 8E7, Canada
| | - Mohit Bhandari
- Division of Orthopaedic Surgery, Department of Surgery, McMaster University & Centre for Evidence Based Orthopaedics, 293 Wellington Street North, Suite 110, Hamilton, Ontario L8L 8E7, Canada
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