Rotator Cuff Tendon Healing Using Human Dermal Fibroblasts: Histological and Biomechanical Analyses in a Rabbit Model of Chronic Rotator Cuff Tears

2021 ◽  
pp. 036354652110411
Author(s):  
Ji-Hye Lee ◽  
Yun Hee Kim ◽  
Sung-Min Rhee ◽  
Jikhyon Han ◽  
Hyeon Jang Jeong ◽  
...  

Background: Tenocytes derived from tendons have been reported to be effective in the treatment of rotator cuff tears through the expression of extracellular matrix proteins. Human dermal fibroblasts, known to express collagen types I and III as tenocytes do, may likely be substitutes for tenocytes to enhance healing rotator cuff tears. Purpose: To demonstrate the capability of human dermal fibroblasts to enhance healing of rotator cuff tears. Study Design: Controlled laboratory study. Methods: The cellular properties and expression profiles of growth factors were compared between human dermal fibroblasts and tenocytes. In both cell types, a series of extracellular matrix proteins were analyzed along with matrix metalloproteinases and tissue inhibitors of metalloproteinases involved in the collagenolytic system. A total of 35 rabbits were divided into 5 groups: normal (n = 2), saline control (n = 9), fibrin control (n = 9), low dose of human fibroblasts (HF-LD; n = 9), and high dose of human fibroblasts (HF-HD; n = 6). Cells were injected into the sutured lesions at 6 weeks after creation of bilateral rotator cuff tears, followed by histological and biomechanical analyses at 12 weeks. Results: Human dermal fibroblasts exhibited a protein expression pattern similar to that of tenocytes. More specifically, the expression levels of collagen types I and III were comparable between fibroblasts and tenocytes. The histological analysis of 30 surviving rabbits showed that collagen fibers were more continuous and better oriented with a more mature interface between the tendon and bone in the sutured lesions in the HF-LD and HF-HD groups. Most importantly, biomechanical strength, measured using the load to failure at the injection site, was 58.8 ± 8.9 N/kg in the HF-HD group, increasing by approximately 2-fold ( P = .0003) over the saline control group. Conclusion: Human dermal fibroblasts, showing cellular properties comparable with tenocytes, effectively enhanced healing of chronic rotator cuff tears in rabbits. Clinical Relevance: Human dermal fibroblasts can be used in place of tenocytes to enhance healing of rotator cuff tears.

2015 ◽  
Vol 24 (12) ◽  
pp. 3884-3891 ◽  
Author(s):  
Birgit Lohberger ◽  
Heike Kaltenegger ◽  
Nicole Stuendl ◽  
Beate Rinner ◽  
Andreas Leithner ◽  
...  

1994 ◽  
Vol 214 (1) ◽  
pp. 381-388 ◽  
Author(s):  
Thilo Sascha Lange ◽  
Anja Katrin Bielinsky ◽  
Katja Kirchberg ◽  
Ilan Bank ◽  
Konrad Herrmann ◽  
...  

2000 ◽  
Vol 68 (9) ◽  
pp. 5210-5217 ◽  
Author(s):  
Sreedhar R. Nallapareddy ◽  
Kavindra V. Singh ◽  
Ruay-Wang Duh ◽  
George M. Weinstock ◽  
Barbara E. Murray

ABSTRACT Our previous work reported that most Enterococcus faecalis strains adhered to the extracellular matrix proteins collagen types I and IV and laminin after growth at 46°C, but not 37°C, and we subsequently identified an E. faecalissequence, ace, that encodes a bacterial adhesin similar to the collagen binding protein Cna of Staphylococcus aureus. In this study, we examined the diversity of E. faecalis-specific ace gene sequences among different isolates obtained from various geographic regions as well as from various clinical sources. A comparison of nucleotide and deduced amino acid sequences of Ace from nine E. faecalis strains identified a highly conserved N-terminal A domain, followed by a variable B domain which contains two to five repeats of 47 amino acids in tandem array, preceded by a 20-amino-acid partial repeat. Using 17 other strains collected worldwide, the 5′ region of acethat encodes the A domain was sequenced, and these sequences showed ≥97.5% identity. Among the previously reported five amino acids critical for collagen binding by Cna of S. aureus, four were found to be identical in Ace from all strains tested. Polyclonal immune rabbit serum prepared against recombinant Ace A derived fromE. faecalis strain OG1RF detected Ace in mutanolysin extracts of seven of nine E. faecalis strains after growth at 46°C; Ace was detected in four different molecular sizes that correspond to the variation in the B repeat region. To determine if there was any evidence to indicate that Ace might be produced under physiological conditions, we quantitatively assayed sera collected from patients with enterococcal infections for the presence of anti-Ace A antibodies. Ninety percent of sera (19 of 21) from patients withE. faecalis endocarditis showed reactivity with titers from 1:32 to >1:1,024; the only 2 sera which lacked antibodies to Ace A had considerably lower titers of antibodies to other E. faecalis antigens as well. Human-derived, anti-Ace A immunoglobulins G purified from an E. faecalis endocarditis patient serum inhibited adherence of 46°C-grown E. faecalis OG1RF to collagen types I and IV and laminin. In conclusion, these results show that ace is highly conserved among isolates of E. faecalis, with at least four variants related to the differences in the B domain, is expressed by different strains during infection in humans, and human-derived antibodies can block adherence to these extracellular matrix proteins.


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