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Cited by 30Tendon Structure and TreatmentKnee injuries and reconstruction techniquesPeriodontal Regeneration and Treatments

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Stem Cell Treatment for Ligament Repair and Reconstruction

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Hevesi, Mario, LaPrade, Matthew, Saris, Daniel B. F., Krych, Aaron J.·2019·Current Reviews in Musculoskeletal Medicine
DOI 10.1007/s12178-019-09580-4PMC PMC6942090
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Abstract

Purpose of review With the rapid and ongoing evolution of regenerative and sports medicine, the use of stem/stromal cells in ligament repair and reconstruction continues to be investigated and grow. The purpose of this review was to assess available methods and formulations for stem/stromal cell augmentation as well as review early pre-clinical and clinical outcomes for these recently emerging techniques. Recent findings Recent literature demonstrates promising outcomes of stem/stromal cell augmentation for ligament repair and reconstruction. Multiple groups have published animal models suggesting improved healing for partially transected ligaments as well as histologic re-approximation of native bone-tendon interfaces with the use of mesenchymal stem/stromal cells in reconstructive models. Human studies also suggest improved outcomes spanning from higher patient-reported outcome scores to magnetic resonance imaging evidence of ligament healing in the setting of anterior cruciate ligament tears. However, clinical studies are only recently available, relatively few in number, and not necessarily accompanied by standard-of-care controls. There is increasing availability and growing animal and clinical evidence demonstrating potential benefit of stem/stromal cell augmentation for tendon healing. However, to date, there is a relative paucity of high-level human evidence for the routine use of stem/stromal cells for ligament repair and reconstruction in the clinical practice. This field contains substantial promise and merits further, ongoing investigation.

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Research works printed but not linked: 45

  1. Petersen W, Tillmann B. Structure and vascularization of the cruciate ligaments of the human knee joint. Anat Embryol (Berl). 1999;200(3):325–34. · DOI
  2. Uchida R, Horibe S, Nakamura N. Stem cell-based therapy in anterior cruciate ligament repair. Ann Jt. 2017;2(11):1–9. · DOI
  3. Robson AW. VI. Ruptured crucial ligaments and their repair by operation. Ann Surg. 1903;37(5):716–8.
  4. Weaver JK, Derkash RS, Freeman JR, Kirk RE, Oden RR, Matyas J. Primary knee ligament repair--revisited. Clin Orthop Relat Res. 1985;199:185–91. · DOI
  5. Sherman MF, Lieber L, Bonamo JR, Podesta L, Reiter I. The long-term follow-up of primary anterior cruciate ligament repair. Defining a rationale for augmentation. Am J Sports Med. 1991;19(3):243–55. · DOI
  6. van der List JP, DiFelice GS. Primary repair of the anterior cruciate ligament: a paradigm shift. Surgeon. 2017;15(3):161–8. · DOI
  7. van der List JP, DiFelice GS. Range of motion and complications following primary repair versus reconstruction of the anterior cruciate ligament. Knee. 2017;24(4):798–807. · DOI
  8. • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–95 Classic and landmark paper describing adipose tissue as a source of multipotent stem cells, leading the establishment and subsequent growth of AMSC literature. · DOI
  9. Lo B, Parham L. Ethical issues in stem cell research. Endocr Rev. 2009;30(3):204–13. · DOI
  10. Sullivan MO, Gordon-Evans WJ, Fredericks LP, Kiefer K, Conzemius MG, Griffon DJ. Comparison of mesenchymal stem cell surface markers from bone marrow aspirates and adipose stromal vascular fraction sites. Front Vet Sci. 2016;2:82. · DOI
  11. Smith J, Hurdle MF, Weingarten TN. Accuracy of sonographically guided intra-articular injections in the native adult hip. J Ultrasound Med. 2009;28(3):329–35. · DOI
  12. Nguyen C, Rannou F. The safety of intra-articular injections for the treatment of knee osteoarthritis: a critical narrative review. Expert Opin Drug Saf. 2017;16(8):897–902. · DOI
  13. Gaujoux-Viala C, Dougados M, Gossec L. Efficacy and safety of steroid injections for shoulder and elbow tendonitis: a meta-analysis of randomised controlled trials. Ann Rheum Dis. 2009;68(12):1843–9. · DOI
  14. Peterson C, Hodler J. Adverse events from diagnostic and therapeutic joint injections: a literature review. Skelet Radiol. 2011;40(1):5–12. · DOI
  15. Murray MM, Flutie BM, Kalish LA, Ecklund K, Fleming BC, Proffen BL, et al. The bridge-enhanced anterior cruciate ligament repair (BEAR) procedure: an early feasibility cohort study. Orthop J Sports Med. 2016;4(11):2325967116672176. · DOI
  16. Kiapour AM, Ecklund K, Murray MM, Flutie B, Freiberger C, Henderson R, et al. Changes in cross-sectional area and signal intensity of healing anterior cruciate ligaments and grafts in the first 2 years after surgery. Am J Sports Med. 2019;47(8):1831–43. · DOI
  17. Murray MM, Kalish LA, Fleming BC, Flutie B, Freiberger C, Henderson RN, et al. Bridge-enhanced anterior cruciate ligament repair: two-year results of a first-in-human study. Orthop J Sports Med. 2019;7(3):2325967118824356. · DOI
  18. Crispim JF, Fu SC, Lee YW, Fernandes HAM, Jonkheijm P, Yung PSH, et al. Bioactive tape with BMP-2 binding peptides captures endogenous growth factors and accelerates healing after anterior cruciate ligament reconstruction. Am J Sports Med. 2018;46(12):2905–14. · DOI
  19. Hevesi M, Paradise CR, Paggi CA, Galeano-Garces C, Dudakovic A, Karperien M, et al. Defining the baseline transcriptional fingerprint of rabbit hamstring autograft. Gene Rep. 2019;15:100363. · DOI
  20. Hevesi M, Crispim JF, Paggi CA, Dudakovic A, van Genechten W, Hewett T, et al. A versatile protocol for studying anterior cruciate ligament reconstruction in a rabbit model. Tissue Eng Part C Methods. 2019;25(4):191–6. · DOI
  21. Heilmann HH, Lindenhayn K, Walther HU. Synovial volume of healthy and arthrotic human knee joints. Z Orthop Ihre Grenzgeb. 1996;134(2):144–8. · DOI
  22. Bianco P. “Mesenchymal” stem cells. Annu Rev Cell Dev Biol. 2014;30:677–704. · DOI
  23. Ekwueme EC, Shah JV, Mohiuddin M, Ghebes CA, Crispim JF, Saris DB, et al. Cross-talk between human tenocytes and bone marrow stromal cells potentiates extracellular matrix remodeling in vitro. J Cell Biochem. 2016;117(3):684–93. · DOI
  24. Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M, Helder MN, Klein-Nulend J, Schouten TE, et al. Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy. 2006;8(2):166–77. · DOI
  25. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 2006;24(4):150–4. · DOI
  26. Tremolada C, Colombo V, Ventura C. Adipose tissue and mesenchymal stem cells: state of the art and Lipogems® technology development. Curr Stem Cell Rep. 2016;2(3):304–12. · DOI
  27. Norelli JB, Plaza DP, Stal DN, Varghese AM, Liang H, Grande DA. Tenogenically differentiated adipose-derived stem cells are effective in Achilles tendon repair in vivo. J Tissue Eng. 2018;9:2041731418811183. · DOI
  28. Torres-Torrillas M, Rubio M, Damia E, Cuervo B, Del Romero A, Peláez P, et al. Adipose-derived mesenchymal stem cells: a promising tool in the treatment of musculoskeletal diseases. Int J Mol Sci. 2019;20(12):3105. · DOI
  29. • Zhou W, Lin J, Zhao K, Jin K, He Q, Hu Y, et al. Single-cell profiles and clinically useful properties of human mesenchymal stem cells of adipose and bone marrow origin. Am J Sports Med. 2019;47(7):1722–33 Direct comparison of same patient BMSCs and AMSCs employing modern RNA sequencing methodology to compare the transcriptional fingerprint of the two stem/stromal cell types. AMSCs demonstrate lower HLA I expression and higher immunosuppression capacity compared with AMSCs. · DOI
  30. de Windt TS, Vonk LA, Slaper-Cortenbach IC, van den Broek MP, Nizak R, van Rijen MH, et al. Allogeneic mesenchymal stem cells stimulate cartilage regeneration and are safe for single-stage cartilage repair in humans upon mixture with recycled autologous chondrons. Stem Cells. 2017;35(1):256–64. · DOI
  31. Dalle JH, Balduzzi A, Bader P, Lankester A, Yaniv I, Wachowiak J, et al. Allogeneic stem cell transplantation from HLA-mismatched donors for pediatric patients with acute lymphoblastic leukemia treated according to the 2003 BFM and 2007 international BFM studies: impact of disease risk on outcomes. Biol Blood Marrow Transplant. 2018;24(9):1848–55. · DOI
  32. Hays PL, Kawamura S, Deng XH, Dagher E, Mithoefer K, Ying L, et al. The role of macrophages in early healing of a tendon graft in a bone tunnel. J Bone Joint Surg Am. 2008;90(3):565–79. · DOI
  33. Hu J, Yao B, Yang X, Ma F. The immunosuppressive effect of Siglecs on tendon-bone healing after ACL reconstruction. Med Hypotheses. 2015;84(1):38–9. · DOI
  34. Kawamura S, Ying L, Kim HJ, Dynybil C, Rodeo SA. Macrophages accumulate in the early phase of tendon-bone healing. J Orthop Res. 2005;23(6):1425–32. · DOI · Paper page
  35. Samitier G, Marcano AI, Alentorn-Geli E, Cugat R, Farmer KW, Moser MW. Failure of anterior cruciate ligament reconstruction. Arch Bone Jt Surg. 2015;3(4):220–40.
  36. Zaffagnini S, Grassi A, Serra M, Marcacci M. Return to sport after ACL reconstruction: how, when and why? A narrative review of current evidence. Joints. 2015;3(1):25–30.
  37. McArdle S. Psychological rehabilitation from anterior cruciate ligament-medial collateral ligament reconstructive surgery: a case study. Sports Health. 2010;2(1):73–7. · DOI
  38. Kanaya A, Deie M, Adachi N, Nishimori M, Yanada S, Ochi M. Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. Arthroscopy. 2007;23(6):610–7. · DOI
  39. Oe K, Kushida T, Okamoto N, Umeda M, Nakamura T, Ikehara S, et al. New strategies for anterior cruciate ligament partial rupture using bone marrow transplantation in rats. Stem Cells Dev. 2011;20(4):671–9. · DOI
  40. Ju YJ, Muneta T, Yoshimura H, Koga H, Sekiya I. Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing. Cell Tissue Res. 2008;332(3):469–78. · DOI
  41. Lim JK, Hui J, Li L, Thambyah A, Goh J, Lee EH. Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy. 2004;20(9):899–910. · DOI · Paper page
  42. • Wang Y, Shimmin A, Ghosh P, Marks P, Linklater J, Connell D, et al. Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial. Arthritis Res Ther. 2017;19(1):180 Human double-blinded randomized control trial demonstrating safety of allogeneic mesenchymal precursor cell injection in the setting of ACL reconstruction, improved patient-reported outcomes, and reduced tibiofemoral joint space narrowing. · DOI
  43. Centeno C, Markle J, Dodson E, Stemper I, Williams C, Hyzy M, et al. 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(1):246. · DOI
  44. • Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, et al. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014;38(9):1811–8 Classic early report of MSCs used in tendon healing, important given the predominance of tendon tissues for ACL reconstruction. Demonstrated improved healing rates and decreased subsequent rotator cuff tears in the MSC group as compared with controls. · DOI
  45. Kim YS, Sung CH, Chung SH, Kwak SJ, Koh YG. Does an injection of adipose-derived mesenchymal stem cells loaded in fibrin glue influence rotator cuff repair outcomes? A clinical and magnetic resonance imaging study. Am J Sports Med. 2017;45(9):2010–8. · DOI

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Metadata

Authors
Hevesi, M., LaPrade, M., Saris, D. B. F., & Krych, A. J.
Affiliations
Mayo Clinic (US)
Corresponding author
Krych, Aaron J.
ORCID
Venue
Current Reviews in Musculoskeletal Medicine
Publisher
Springer Science and Business Media LLC
Published
2019-10-17
Volume
12
Issue
4
Pages
446-450
ISSN
  • 1935-973X (ISSN-L)
  • 1935-9748
DOI
10.1007/s12178-019-09580-4
PMC
PMC6942090
OpenAlex
W2980317017
Cited by
30
References
0
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 5 · 2020: 3
FWCI
0.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Reviews in Musculoskeletal Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
  • Health Sciences › Medicine › Surgery › Knee injuries and reconstruction techniques
  • Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
Keywords
stem cell therapy, ligament repair, ligament reconstruction, mesenchymal stem cells, stromal cells, anterior cruciate ligament rupture, tendon healing, tendon-bone interface, patient-reported outcomes

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