Muscle‐secreted factors improve anterior cruciate ligament graft healing: an in vitro and in vivo analysis
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Officially Accepted for Publication


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AbstractOne of the ligaments most often damaged during sports – the anterior cruciate ligament (ACL) – has poor healing capacity. Upon damage, reconstructive surgery is performed to restore the mechanical stability of the knee and to reduce the inflammatory milieu otherwise present in the joint. A return to normal activities, however, takes between 9 and 12 months. Thus, strategies capable of improving ACL graft healing are needed.
Embryonic development of tendon and ligament (T/L) is regulated by a crosstalk between different cell types. We hypothesised that terminally-differentiated skeletal derived cells such as osteoblasts, chondrocytes and myoblasts modulate T/L healing. Using an indirect co-culture system, we discovered that myoblast-secreted signals – but not osteoblasts, chondrocytes, or stromal-secreted signals - are capable of upregulating classical T/L markers such as Scleraxis and Tenomodulin on human hamstring tendon-derived cells (hTC), which contribute to ACL graft healing. Whole transcriptome analysis showed that co-culturing hTC with myoblasts led to an upregulation of extracellular matrix (ECM) genes and resulted in enhanced ECM deposition. In vivo, using a rat model of ACL reconstruction, showed that conditioned media derived from human muscle tissue accelerated femoral tunnel closure, a key step for autograft integration. Collectively, these results indicate that muscle-secreted signals can be employed to improve ACL graft healing in a clinical setting where muscle remnants are often discarded.
Acceptance Date18/05/2017
All Author(s) ListGhebes CA, Groen N, Cheuk YC, Fu SC, Fernandes H, Saris DB
Journal nameTissue Engineering: Parts A, B, and C
Year2017
PublisherMary Ann Liebert, Inc.
ISSN1937-3368
eISSN1937-335X
LanguagesEnglish-United States

Last updated on 2020-18-10 at 00:45