Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Knee Surgery, Sports Traumatology, Arthroscopy
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 5/2014

01-05-2014 | Experimental Study

Anterior cruciate ligament regeneration using mesenchymal stem cells and collagen type I scaffold in a rabbit model

Authors: David Figueroa, Maximiliano Espinosa, Rafael Calvo, Maximiliano Scheu, Alex Vaisman, Marcela Gallegos, Paulette Conget

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 5/2014

Login to get access

Abstract

Purpose

The objective of this study was to determine whether using mesenchymal stem cells (MSC) seeded in a collagen type I scaffold would be sufficient to regenerate the torn anterior cruciate ligament (ACL).

Methods

Anterior cruciate ligament transection was performed on both knees in 10 New Zealand rabbits and then repaired with as follows: suture alone (suture-treated group, n = 6), suture associated with collagen type I scaffold (collagen type I scaffold-treated group, n = 8) or suture associated with autologous MSC seeded on collagen type I scaffold (MSC/collagen type I scaffold-treated group, n = 6). At 12-week post-intervention, the animals were killed and the ACLs were characterised macroscopically and histologically. Data of the 3 groups were against normal ACL (normal group, n = 10).

Results

Macroscopic observation found that in MSC/collagen type I scaffold group, 33 % of specimens showed a complete ACL regeneration, with a tissue similar to the normal ACL. Regeneration was not observed in the group treated with suture alone or associated with collagen type I scaffold without cells. In the latter, only a reparative attempt at the ends was observed. Histological analysis of the regenerated ACL showed a tissue with organised collagen and peripheric vessels.

Conclusions

These results provide evidence that the use of MSC seeded in a collagen type I scaffold in the treatment of ACL injuries is associated with an enhancement of ligament regeneration. This MSC-based technique is a potentially attractive tool for improving the treatment of ACL ruptures.
Literature
1.
Amiel D, Nagineni CN, Choi SH, Lee J (1995) Intrinsic properties of ACL and MCL cells and their responses to growth factors. Med Sci Sports Exerc 27:844–851PubMedCrossRef
2.
Bellincampi LD, Closkey RF, Prasad R, Zawadsky JP, Dunn MG (1998) Viability of fibroblast-seeded ligament analogs after autogenous implantation. J Orthop Res 16:414–420PubMedCrossRef
3.
Breyner NM, Hell RCR, Carvalho LRP, Machado CB, Peixoto Filho IN, Valério P, Pereira MM, Goes AM (2010) Effect of a three-dimensional chitosan porous scaffold on the differentiation of mesenchymal stem cells into chondrocytes. Cells Tissues Organs 191:119–128PubMedCrossRef
4.
Chamberlain G, Fox J, Ashton B, Middleton J (2007) Concise review: mesenchymal stem cells—their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25:2739–2749PubMedCrossRef
5.
Conget PA, Minguell JJ (1999) Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181:67–73PubMedCrossRef
6.
Crawford C, Kainer M, Jernigan D, Banerjee S, Friedman C, Ahmed F, Archibald LK (2005) Investigation of postoperative allograft-associated infections in patients who underwent musculoskeletal allograft implantation. Clin Infect Dis 41:195–200PubMedCrossRef
7.
Darabos N, Hundric-Haspl Z, Haspl M, Markotic A, Darabos A, Moser C (2009) Correlation between synovial fluid and serum IL-1β levels after ACL surgery-preliminary report. Int Orthop 33:413–418PubMedCentralPubMedCrossRef
8.
Darabos N, Haspl M, Moser C, Darabos A, Bartolek D, Groenemeyer D (2011) Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc 19(Suppl 1):S36–S46PubMedCrossRef
9.
Dunn MG, Liesch JB, Tiku ML, Zawadsky JP (1995) Development of fibroblast-seeded ligament analogs for ACL reconstruction. J Biomed Mater Res 29:1363–1371PubMedCrossRef
10.
Fan H, Liu H, Toh SL, Goh JCH (2009) Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model. Biomaterials 30:4967–4977PubMedCrossRef
11.
Fisher MB, Liang R, Jung H-J, Kim KE, Zamarra G, Almarza AJ, McMahon PJ, Woo SL-Y (2012) Potential of healing a transected anterior cruciate ligament with genetically modified extracellular matrix bioscaffolds in a goat model. Knee Surg Sports Traumatol Arthrosc 20:1357–1365PubMedCrossRef
12.
Fleming BC, Spindler KP, Palmer MP, Magarian EM, Murray MM (2009) Collagen-platelet composites improve the biomechanical properties of healing anterior cruciate ligament grafts in a porcine model. Am J Sports Med 37:1554–1563PubMedCentralPubMedCrossRef
13.
Frobell RB, Lohmander LS, Roos HP (2007) Acute rotational trauma to the knee: poor agreement between clinical assessment and magnetic resonance imaging findings. Scand J Med Sci Sports 17:109–114PubMed
14.
Ge Z, Goh JCH, Lee EH (2005) Selection of cell source for ligament tissue engineering. Cell Transpl 14:573–583CrossRef
15.
Hoffelner T, Resch R, Moroder P et al (2012) No increased occurrence of osteoarthritis after anterior cruciate ligament reconstruction after isolated anterior cruciate ligament injury in athletes. Arthroscopy 28:517–525PubMedCrossRef
16.
Joshi SM, Mastrangelo AN, Magarian EM, Fleming BC, Murray MM (2009) Collagen-platelet composite enhances biomechanical and histologic healing of the porcine anterior cruciate ligament. Am J Sports Med 37:2401–2410PubMedCentralPubMedCrossRef
17.
Kobayashi K, Healey RM, Sah RL, Clark JJ, Tu BP, Goomer RS, Akeson WH, Moriya H, Amiel D (2000) Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells. Tissue Eng 6:29–38PubMedCrossRef
18.
Liu H, Fan H, Toh SL, Goh JCH (2008) A comparison of rabbit mesenchymal stem cells and anterior cruciate ligament fibroblasts responses on combined silk scaffolds. Biomaterials 29:1443–1453PubMedCrossRef
19.
Mastrokalos DS, Springer J, Siebold R, Paessler HH (2005) Donor site morbidity and return to the preinjury activity level after anterior cruciate ligament reconstruction using ipsilateral and contralateral patellar tendon autograft: a retrospective, nonrandomized study. Am J Sports Med 33:85–93PubMedCrossRef
20.
Minguell JJ, Erices A, Conget P (2001) Mesenchymal stem cells. Exp Biol Med (Maywood) 226:507–520
21.
Murray MM, Martin SD, Martin TL, Spector M (2000) Histological changes in the human anterior cruciate ligament after rupture. J Bone Joint Surg Am 82-A:1387–1397PubMed
22.
Murray MM, Spindler KP, Devin C, Snyder BS, Muller J, Takahashi M, Ballard P, Nanney LB, Zurakowski D (2006) Use of a collagen-platelet rich plasma scaffold to stimulate healing of a central defect in the canine ACL. J Orthop Res 24:820–830PubMedCrossRef
23.
Murray MM, Palmer M, Abreu E, Spindler KP, Zurakowski D, Fleming BC (2009) Platelet-rich plasma alone is not sufficient to enhance suture repair of the ACL in skeletally immature animals: an in vivo study. J Orthop Res 27:639–645PubMedCentralPubMedCrossRef
24.
25.
Nagineni CN, Amiel D, Green MH, Berchuck M, Akeson WH (1992) Characterization of the intrinsic properties of the anterior cruciate and medial collateral ligament cells: an in vitro cell culture study. J Orthop Res 10:465–475PubMedCrossRef
26.
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74PubMedCrossRef
27.
Rość D, Powierza W, Zastawna E, Drewniak W, Michalski A, Kotschy M (2002) Post-traumatic plasminogenesis in intraarticular exudate in the knee joint. Med Sci Monit 8:371–378
28.
Spindler KP, Clark SW, Nanney LB, Davidson JM (1996) Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study. J Orthop Res 14:857–861PubMedCrossRef
29.
Vavken P, Fleming BC, Mastrangelo AN, Machan JT, Murray MM (2012) Biomechanical outcomes after bioenhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction are equal in a porcine model. Arthroscopy 28:672–680PubMedCentralPubMedCrossRef
30.
von Porat A, Roos EM, Roos H (2004) High prevalence of osteoarthritis 14 years after an anterior cruciate ligament tear in male soccer players: a study of radiographic and patient relevant outcomes. Ann Rheum Dis 63:269–273CrossRef
31.
Wang Y, Kim U-J, Blasioli DJ, Kim H-J, Kaplan DL (2005) In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells. Biomaterials 26:7082–7094PubMedCrossRef
32.
Metadata
Title
Anterior cruciate ligament regeneration using mesenchymal stem cells and collagen type I scaffold in a rabbit model
Authors
David Figueroa
Maximiliano Espinosa
Rafael Calvo
Maximiliano Scheu
Alex Vaisman
Marcela Gallegos
Paulette Conget
Publication date
01-05-2014
Publisher
Springer Berlin Heidelberg
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 5/2014
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-013-2471-6

Other articles of this Issue 5/2014

Knee Surgery, Sports Traumatology, Arthroscopy 5/2014 Go to the issue

Knee

ACL reconstruction with physiological graft tension by intraoperative adjustment of the anteroposterior translation to the uninjured contralateral knee

Knee

Graft size after anterior cruciate ligament reconstruction

Knee

Effects of Wii balance board exercises on balance after posterior cruciate ligament reconstruction

Knee

Revision of anterior cruciate ligament reconstruction with allografts in patients younger than 40 years old: a 2 to 4 year results

Knee

Long-term follow-up of ACL reconstruction with hamstring autograft

Knee

Use of the short form health surveys as an outcome measure for anterior cruciate ligament reconstruction