Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure—Evaluation of an In Vivo Model
Abstract
:1. Introduction
2. Results
2.1. Meniscus Suture with PRP—6 Weeks
2.2. Meniscus Suture with BMAC—6 Weeks
2.3. Meniscus Suture with PRP—12 Weeks
2.4. Meniscus Suture with BMAC—12 Weeks
2.5. Meniscus Scoring
3. Discussion
4. Material and Methods
4.1. Study Design
4.2. Bone Marrow Harvest and Bone Marrow Aspirate Concentrate Preparation
4.3. Harvest of Platelet-Rich Plasma and Preparation
4.4. Surgical Procedure for Meniscal Tears
4.5. Assessment of the Menisci
4.6. Histology
4.7. Immunohistochemistry
Type II Collagen
4.8. Meniscus Scoring System
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Mordecai, S.C.; Al-Hadithy, N.; Ware, H.E.; Gupte, C.M. Treatment of meniscal tears: An evidence based approach. World J. Orthop. 2014, 5, 233–241. [Google Scholar] [CrossRef] [PubMed]
- McNulty, A.L.; Guilak, F. Mechanobiology of the meniscus. J. Biomech. 2015, 48, 1469–1478. [Google Scholar] [CrossRef] [PubMed]
- Wei, L.C.; Gao, S.G.; Xu, M.; Jiang, W.; Tian, J.; Lei, G.H. A novel hypothesis: The application of platelet-rich plasma can promote the clinical healing of white-white meniscal tears. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2012, 18, HY47–HY50. [Google Scholar] [CrossRef]
- Taylor, S.A.; Rodeo, S.A. Augmentation techniques for isolated meniscal tears. Curr. Rev. Musculoskelet. Med. 2013, 6, 95–101. [Google Scholar] [CrossRef] [PubMed]
- Niu, W.; Guo, W.; Han, S.; Zhu, Y.; Liu, S.; Guo, Q. Cell-Based Strategies for Meniscus Tissue Engineering. Stem Cells Int. 2016, 2016, 4717184. [Google Scholar] [CrossRef] [PubMed]
- Achatz, F.; Kujat, R.; Pfeifer, C.; Koch, M.; Nerlich, M.; Angele, P.; Zellner, J. In Vitro Testing of Scaffolds for Mesenchymal Stem Cell-Based Meniscus Tissue Engineering—Introducing a New Biocompatibility Scoring System. Materials 2016, 9, 276. [Google Scholar] [CrossRef] [PubMed]
- Yoon, K.H.; Park, K.H. Meniscal repair. Knee Surg. Relat. Res. 2014, 26, 68–76. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, A.M.; Burke, D.L. In-vitro measurement of static pressure distribution in synovial joints--Part I: Tibial surface of the knee. J. Biomech. Eng. 1983, 105, 216–225. [Google Scholar] [CrossRef] [PubMed]
- Petty, C.A.; Lubowitz, J.H. Does arthroscopic partial meniscectomy result in knee osteoarthritis? A systematic review with a minimum of 8 years’ follow-up. Arthrosc. J. Arthrosc. Relat. Surg. 2011, 27, 419–424. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.; Toma, I.C.; Mastrogiacomo, M.; Krettek, C.; Lewinski, G.; Jagodzinski, M. Meniscus reconstruction: Today’s achievements and premises for the future. Arch. Orthop. Trauma Surg. 2013, 133, 95–109. [Google Scholar] [CrossRef] [PubMed]
- Brindle, T.; Nyland, J.; Johnson, D.L. The meniscus: Review of basic principles with application to surgery and rehabilitation. J. Athlet.Train. 2001, 36, 160–169. [Google Scholar]
- Koch, M.; Achatz, F.P.; Lang, S.; Pfeifer, C.G.; Pattappa, G.; Kujat, R.; Nerlich, M.; Angele, P.; Zellner, J. Tissue Engineering of Large Full-Size Meniscus Defects by a Polyurethane Scaffold: Accelerated Regeneration by Mesenchymal Stromal Cells. Stem Cells Int. 2018, 2018, 8207071. [Google Scholar] [CrossRef] [PubMed]
- Vrancken, A.C.; Buma, P.; van Tienen, T.G. Synthetic meniscus replacement: A review. Int. Orthop. 2013, 37, 291–299. [Google Scholar] [CrossRef] [PubMed]
- Beaufils, P.; Pujol, N. Meniscal repair: Technique. Orthop. Traumatol. Surg. Res. 2018, 104, S137–S145. [Google Scholar] [CrossRef] [PubMed]
- Steadman, J.R.; Matheny, L.M.; Singleton, S.B.; Johnson, N.S.; Rodkey, W.G.; Crespo, B.; Briggs, K.K. Meniscus suture repair: Minimum 10-year outcomes in patients younger than 40 years compared with patients 40 and older. Am. J. Sports Med. 2015, 43, 2222–2227. [Google Scholar] [CrossRef] [PubMed]
- Koch, M.; Ehrenreich, T.; Koehl, G.; Pattappa, G.; Pfeifer, C.; Loibl, M.; Muller, M.; Nerlich, M.; Angele, P.; Zellner, J. Do cell based Tissue Engineering products for meniscus regeneration influence vascularization? Clin. Hemorheol. Microcirc. 2017. [Google Scholar] [CrossRef] [PubMed]
- Petersen, W.; Pufe, T.; Starke, C.; Fuchs, T.; Kopf, S.; Raschke, M.; Becker, R.; Tillmann, B. Locally applied angiogenic factors—A new therapeutic tool for meniscal repair. Ann. Anat. 2005, 187, 509–519. [Google Scholar] [CrossRef] [PubMed]
- Angele, P.; Kujat, R.; Koch, M.; Zellner, J. Role of mesenchymal stem cells in meniscal repair. J. Exp. Orthop. 2014, 1, 12. [Google Scholar] [CrossRef] [PubMed]
- Angele, P.; Johnstone, B.; Kujat, R.; Zellner, J.; Nerlich, M.; Goldberg, V. Stem cell based tissue engineering for meniscus repair. J. Biomed. Mater. Res. A 2008, 85. [Google Scholar] [CrossRef] [PubMed]
- Zellner, J.; Hierl, K.; Mueller, M.; Pfeifer, C.; Berner, A.; Dienstknecht, T.; Krutsch, W.; Geis, S.; Gehmert, S.; Kujat, R.; et al. Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone. J. Biomed. Materials Res. Part B Appl. Biomater. 2013, 101, 1133–1142. [Google Scholar] [CrossRef] [PubMed]
- Zellner, J.; Mueller, M.; Berner, A.; Dienstknecht, T.; Kujat, R.; Nerlich, M.; Hennemann, B.; Koller, M.; Prantl, L.; Angele, M.; et al. Role of mesenchymal stem cells in tissue engineering of meniscus. J. Biomed. Mater. Res. Part A 2010, 94, 1150–1161. [Google Scholar] [CrossRef] [PubMed]
- Zellner, J.; Taeger, C.D.; Schaffer, M.; Roldan, J.C.; Loibl, M.; Mueller, M.B.; Berner, A.; Krutsch, W.; Huber, M.K.; Kujat, R.; et al. Are applied growth factors able to mimic the positive effects of mesenchymal stem cells on the regeneration of meniscus in the avascular zone? BioMed Res. Int. 2014, 2014, 537686. [Google Scholar] [CrossRef] [PubMed]
- Korpershoek, J.V.; de Windt, T.S.; Hagmeijer, M.H.; Vonk, L.A.; Saris, D.B. Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation? A Systematic Review of Preclinical Studies. Orthop. J. Sports Med. 2017, 5. [Google Scholar] [CrossRef] [PubMed]
- Voss, A.; McCarthy, M.B.; Allen, D.; Cote, M.P.; Beitzel, K.; Imhoff, A.B.; Mazzocca, A.D. Fibrin Scaffold as a Carrier for Mesenchymal Stem Cells and Growth Factors in Shoulder Rotator Cuff Repair. Arthrosc. Tech. 2016, 5, e447–e451. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Kilpatrick, C.D.; Smith, S.; Glettig, D.L.; Glod, D.J.; Mallette, J.; Strunk, M.R.; Chang, J.; Angle, S.R.; Kaplan, D.L. Assessment of Multipotent Mesenchymal Stromal Cells in Bone Marrow Aspirate From Human Calcaneus. J. Foot Ankle Surg. 2017, 56, 42–46. [Google Scholar] [CrossRef] [PubMed]
- Dragoo, J.L.; DeBaun, M.R. Stem Cell Yield after Bone Marrow Concentration. Orthop. J. Sports Med. 2017, 5. [Google Scholar] [CrossRef]
- Holton, J.; Imam, M.; Ward, J.; Snow, M. The Basic Science of Bone Marrow Aspirate Concentrate in Chondral Injuries. Orthop. Rev. 2016, 8, 6659. [Google Scholar] [CrossRef] [PubMed]
- Moatshe, G.; Morris, E.R.; Cinque, M.E.; Pascual-Garrido, C.; Chahla, J.; Engebretsen, L.; Laprade, R.F. Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates. Acta Orthop. 2017, 88, 670–674. [Google Scholar] [CrossRef] [PubMed]
- Gobbi, A.; Chaurasia, S.; Karnatzikos, G.; Nakamura, N. Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial. Cartilage 2015, 6, 82–97. [Google Scholar] [CrossRef] [PubMed]
- Caplan, A.I.; Dennis, J.E. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 2006, 98, 1076–1084. [Google Scholar] [CrossRef] [PubMed]
- Baraniak, P.R.; McDevitt, T.C. Stem cell paracrine actions and tissue regeneration. Regen. Med. 2010, 5, 121–143. [Google Scholar] [CrossRef] [PubMed]
- Yu, H.; Adesida, A.B.; Jomha, N.M. Meniscus repair using mesenchymal stem cells—A comprehensive review. Stem Cell Res. Ther. 2015, 6, 86. [Google Scholar] [CrossRef] [PubMed]
- Pak, J.; Lee, J.H.; Park, K.S.; Jeon, J.H.; Lee, S.H. Potential use of mesenchymal stem cells in human meniscal repair: Current insights. Open Access J. Sports Med. 2017, 8, 33–38. [Google Scholar] [CrossRef] [PubMed]
- Zwaginga, J.J.; Doevendans, P. Stem cell-derived angiogenic/vasculogenic cells: Possible therapies for tissue repair and tissue engineering. Clin. Exp. Pharmacol. Physiol. 2003, 30, 900–908. [Google Scholar] [CrossRef] [PubMed]
- Tang, Y.L.; Qian, K.; Zhang, Y.C.; Shen, L.; Phillips, M.I. Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regul. Pept. 2005, 125, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Tang, Y.L.; Zhao, Q.; Zhang, Y.C.; Cheng, L.; Liu, M.; Shi, J.; Yang, Y.Z.; Pan, C.; Ge, J.; Phillips, M.I. Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul. Pept. 2004, 117, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Murphy, J.M.; Fink, D.J.; Hunziker, E.B.; Barry, F.P. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003, 48, 3464–3474. [Google Scholar] [CrossRef] [PubMed]
- Zellner, J.; Pattappa, G.; Koch, M.; Lang, S.; Weber, J.; Pfeifer, C.G.; Mueller, M.B.; Kujat, R.; Nerlich, M.; Angele, P. Autologous mesenchymal stem cells or meniscal cells: What is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation? Stem Cell Res. Ther. 2017, 8, 225. [Google Scholar] [CrossRef] [PubMed]
- Horie, M.; Choi, H.; Lee, R.H.; Reger, R.L.; Ylostalo, J.; Muneta, T.; Sekiya, I.; Prockop, D.J. Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthr. Cartil. 2012, 20, 1197–1207. [Google Scholar] [CrossRef] [PubMed]
- Kambic, H.E.; McDevitt, C.A. Spatial organization of types I and II collagen in the canine meniscus. J. Orthop. Res. 2005, 23, 142–149. [Google Scholar] [CrossRef] [PubMed]
- Makris, E.A.; Hadidi, P.; Athanasiou, K.A. The knee meniscus: Structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials 2011, 32, 7411–7431. [Google Scholar] [CrossRef] [PubMed]
- Whitehouse, M.R.; Howells, N.R.; Parry, M.C.; Austin, E.; Kafienah, W.; Brady, K.; Goodship, A.E.; Eldridge, J.D.; Blom, A.W.; Hollander, A.P. Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study. Stem Cells Transl. Med. 2017, 6, 1237–1248. [Google Scholar] [CrossRef] [PubMed]
- Chahla, J.; Dean, C.S.; Moatshe, G.; Pascual-Garrido, C.; Serra Cruz, R.; LaPrade, R.F. Concentrated Bone Marrow Aspirate for the Treatment of Chondral Injuries and Osteoarthritis of the Knee: A Systematic Review of Outcomes. Orthop. J. Sports Med. 2016, 4. [Google Scholar] [CrossRef] [PubMed]
- Ishida, K.; Kuroda, R.; Miwa, M.; Tabata, Y.; Hokugo, A.; Kawamoto, T.; Sasaki, K.; Doita, M.; Kurosaka, M. The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. Tissue Eng. 2007, 13, 1103–1112. [Google Scholar] [CrossRef] [PubMed]
- Sanchez, M.; Delgado, D.; Sanchez, P.; Fiz, N.; Azofra, J.; Orive, G.; Anitua, E.; Padilla, S. Platelet rich plasma and knee surgery. BioMed Res. Int. 2014, 2014, 890630. [Google Scholar] [CrossRef] [PubMed]
- Kaminski, R.; Kulinski, K.; Kozar-Kaminska, K.; Wielgus, M.; Langner, M.; Wasko, M.K.; Kowalczewski, J.; Pomianowski, S. A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating Meniscal Healing, Clinical Outcomes, and Safety in Patients Undergoing Meniscal Repair of Unstable, Complete Vertical Meniscal Tears (Bucket Handle) Augmented with Platelet-Rich Plasma. BioMed Res. Int. 2018, 2018, 9315815. [Google Scholar] [CrossRef] [PubMed]
- Pujol, N.; Salle De Chou, E.; Boisrenoult, P.; Beaufils, P. Platelet-rich plasma for open meniscal repair in young patients: Any benefit? Knee Surg. Sports Traumatol. Arthrosc. 2015, 23, 51–58. [Google Scholar] [CrossRef] [PubMed]
- Shin, K.H.; Lee, H.; Kang, S.; Ko, Y.J.; Lee, S.Y.; Park, J.H.; Bae, J.H. Effect of Leukocyte-Rich and Platelet-Rich Plasma on Healing of a Horizontal Medial Meniscus Tear in a Rabbit Model. BioMed Res. Int. 2015, 2015, 179756. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.R.; Shon, O.J.; Park, S.I.; Kim, H.J.; Kim, S.; Ahn, M.W.; Do, S.H. Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model. Int. J. Mol. Sci. 2016, 17, 120. [Google Scholar] [CrossRef] [PubMed]
- Griffin, J.W.; Hadeed, M.M.; Werner, B.C.; Diduch, D.R.; Carson, E.W.; Miller, M.D. Platelet-rich plasma in meniscal repair: Does augmentation improve surgical outcomes? Clin. Orthop. Relat. Res. 2015, 473, 1665–1672. [Google Scholar] [CrossRef] [PubMed]
- Mishra, A.; Tummala, P.; King, A.; Lee, B.; Kraus, M.; Tse, V.; Jacobs, C.R. Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng. Part C Methods 2009, 15, 431–435. [Google Scholar] [CrossRef] [PubMed]
- Lucarelli, E.; Beccheroni, A.; Donati, D.; Sangiorgi, L.; Cenacchi, A.; Del Vento, A.M.; Meotti, C.; Bertoja, A.Z.; Giardino, R.; Fornasari, P.M.; et al. Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials 2003, 24, 3095–3100. [Google Scholar] [CrossRef]
- Muraglia, A.; Todeschi, M.R.; Papait, A.; Poggi, A.; Spano, R.; Strada, P.; Cancedda, R.; Mastrogiacomo, M. Combined platelet and plasma derivatives enhance proliferation of stem/progenitor cells maintaining their differentiation potential. Cytotherapy 2015, 17, 1793–1806. [Google Scholar] [CrossRef] [PubMed]
- Liao, H.T.; James, I.B.; Marra, K.G.; Rubin, J.P. The Effects of Platelet-Rich Plasma on Cell Proliferation and Adipogenic Potential of Adipose-Derived Stem Cells. Tissue Eng. Part A 2015, 21, 2714–2722. [Google Scholar] [CrossRef] [PubMed]
- Kakudo, N.; Minakata, T.; Mitsui, T.; Kushida, S.; Notodihardjo, F.Z.; Kusumoto, K. Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts. Plast. Reconstr. Surg. 2008, 122, 1352–1360. [Google Scholar] [CrossRef] [PubMed]
- Muhammad, H.; Schminke, B.; Bode, C.; Roth, M.; Albert, J.; von der Heyde, S.; Rosen, V.; Miosge, N. Human migratory meniscus progenitor cells are controlled via the TGF-beta pathway. Stem Cell Rep. 2014, 3, 789–803. [Google Scholar] [CrossRef] [PubMed]
- Lee, K.; Hasei, J.; Olmer, M.; Baek, J.; Alvarez-Garcia, O.; Asahara, H.; D’Lima, D.; Lotz, M. Induction of Mesenchymal Stem Cell Differentiation to a Meniscus Cell Phenotype by a Combination of Mohawk Transcription Factor and TGF-ß For Meniscus Repair and Regeneration. Osteoarthr. Cartil. 2017, 25, S283. [Google Scholar] [CrossRef]
- Vadala, G.; Di Martino, A.; Russo, F.; Tirindelli, M.C.; De Felice, L.; Agostini, F.; Papalia, R.; Denaro, V. Autologous bone marrow concentrate combined with platelet-rich plasma enhance bone allograft potential to induce spinal fusion. J. Biol. Regul. Homeost. Agents 2016, 30, 165–172. [Google Scholar] [PubMed]
- Lee, D.H.; Ryu, K.J.; Kim, J.W.; Kang, K.C.; Choi, Y.R. Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin. Orthop. Relat. Res. 2014, 472, 3789–3797. [Google Scholar] [CrossRef] [PubMed]
Group | Treatment | 6 Weeks | 12 Weeks | ||
---|---|---|---|---|---|
PRP | meniscus suture | + | clotted PRP | 6 animals, right knee | 6 animals, right knee |
BMAC | clotted BMAC | 6 animals, right knee | 6 animals, right knee | ||
control | − | each contralateral knee | each contralateral knee |
Scoring Subgroup | 0 | 1 | 2 | 3 |
---|---|---|---|---|
Defect filling | No fill | <25% | 25–75% | >75% |
Surface | No surface | Ruptured | Fissured/fibrillated | Meniscus-like |
Integration | No integration | Partial, unilateral integration | Bilateral partial or unilateral complete integration | Bilateral complete integration |
Cellularity | No cells | >10 Cell clusters/slide | No cell clusters/slide, Cell/ECM ratio >0.5 | Meniscus-like cell/ECM ratio |
Cell morphology | No cells | <25% Meniscus-like cells | 25–75% Meniscus-like cells | >75% Meniscus-like cells |
Content of proteoglycan | No staining for proteoglycan | <25% | 25–75% | >75% |
Content of collagen II | No staining for collagen II | <25% | 25–75% | >75% |
Stability | No stability | Weak | Stable in shape | Stable to pressure and pulling stress |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Koch, M.; Hammer, S.; Fuellerer, J.; Lang, S.; Pfeifer, C.G.; Pattappa, G.; Weber, J.; Loibl, M.; Nerlich, M.; Angele, P.; et al. Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure—Evaluation of an In Vivo Model. Int. J. Mol. Sci. 2019, 20, 1120. https://doi.org/10.3390/ijms20051120
Koch M, Hammer S, Fuellerer J, Lang S, Pfeifer CG, Pattappa G, Weber J, Loibl M, Nerlich M, Angele P, et al. Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure—Evaluation of an In Vivo Model. International Journal of Molecular Sciences. 2019; 20(5):1120. https://doi.org/10.3390/ijms20051120
Chicago/Turabian StyleKoch, Matthias, Selma Hammer, Julian Fuellerer, Siegmund Lang, Christian G. Pfeifer, Girish Pattappa, Johannes Weber, Markus Loibl, Michael Nerlich, Peter Angele, and et al. 2019. "Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure—Evaluation of an In Vivo Model" International Journal of Molecular Sciences 20, no. 5: 1120. https://doi.org/10.3390/ijms20051120