α‐Smooth muscle actin is expressed by fibroblastic cells of the ovine anterior cruciate ligament and its free tendon graft during remodeling

Abstract

Contractile fibroblastic cells expressing the a-smooth muscle actin isoform, so-called myofibroblasts, have been identified to play a possible role during the healing of the medial collateral ligament by means of restoring the tissues in situ strain via extracellular matrix contraction. Recently, these cells have also been identified to be a normal part of the human anterior cruciate ligament. It has been hypothesized that myofibroblasts play a role in the wrinkling of the extracellular matrix. The goal of the present study was to identify myofibroblasts in the intact ovine anterior cruciate ligament and a free autologous tendon graft during remodeling after anterior cruciate ligament reconstruction. In 36 mature merino sheep the anterior cruciate ligament was replaced with an ipsilateral Achilles tendon split graft. Midsubstance tissue samples were immunostained for a-smooth muscle actin at 6,9, 12,24, 52, and 104 weeks. Myofibroblasts were identified in the intact ovine anterior cruciate ligament as well as in the Achilles tendon graft prior to implantation. During remodeling the first myofibroblasts were found at six weeks within newly formed fiber bundles. At 24, 52, and 104 weeks myofibroblast distribution and cell density were similar to those of the intact ovine anterior cruciate ligament. These findings indicate that a-smooth muscle actin containing fibroblastic cells are a regular part of the intact as well as the remodeled anterior cruciate ligament. There is evidence that myofibroblasts may be involved in maintaining tissue homeostasis in the mature ligament e.g., by means of crimp formation. The presence of these cells during the early remodeling may further indicate that asmooth muscle actin containing fibroblastic cells are involved in the earliest stages of fiber bundle formation. The role and function of this special cell type for the anterior cruciate ligament needs to be further clarified.

Modulating microfibrillar alignment and growth factor stimulation to regulate mesenchymal stem cell differentiation

“…ACTA2 was also more strongly expressed in the CTGF-stimulated cells. Previous studies have shown that fibroblasts expressing ACTA2 are involved in the earliest stages of fiber bundle formation in the intact as well as the remodelled human ACL [46,47].…”

Integración tendinosa de plastias autólogas en túneles de diferente calibre. Estudio experimental en ovejas

“…Estos fibroblastos contráctiles se expresan progresivamente en la plastia durante los tres primeros meses después de la cirugía [161][209] [246], por lo que se les considera los responsables de restaurar la tensión que se requiere para el proceso de "ligamentización".…”

“…Otros autores relacionan el aumento de vasos [246] y la infiltracion extracelular [228] con la disminución de las propiedades mecánicas de la plastia. Estos hallazgos avalan otros muchos trabajos que encuentran que las propiedades mecánicas son mínimas en la fase de proliferación del injerto, aproximadamente entre la 6ª y 8ª Es un proceso de debilitamiento de la plastia hasta la 6ª semana que por otra parte mejora la integración del injerto en la plastia.…”

“…Los miofibroblastos se activan después de una lesión y tienen una función en la contracción de la herida y en la remodelación de la matriz pericelular [175][232] [246].…”

Autologous transplantation of culture-born myofibroblasts into intact and injured rabbit ligaments

“…Myofibroblasts, identified as α-smooth muscle actin (α-SMA)-positive fibroblasts [15,16], have been observed in normal and healing tendons [17,18] [19] and in the intact and injured human ACL [20][21][22]. They contribute substantially to the contractile phase of MCL healing, allowing recovery of its original length [23].…”