Migrating Myofibroblastic Iliotibial Band-Derived Fibroblasts Represent a Promising Cell Source for Ligament Reconstruction.

Schwarz Schwarz,Hammer Hammer,Ondruschka Ondruschka,Schulze-Tanzil Schulze-Tanzil,Gögele Gögele,Kohl Kohl

doi:10.3390/ijms20081972

Abstract

The iliotibial band (ITB) is a suitable scaffold for anterior cruciate ligament (ACL) reconstruction, providing a sufficient mechanical resistance to loading. Hence, ITB-derived fibroblasts attract interest for ligament tissue engineering but have so far not been characterized. This present study aimed at characterizing ITB fibroblasts before, during, and after emigration from cadaveric ITB explants to decipher the emigration behavior and to utilize their migratory capacity for seeding biomaterials. ITB and, for comparison, ACL tissues were assessed for the content of alpha smooth muscle actin (αSMA) expressing fibroblasts and degeneration. The cell survival and αSMA expression were monitored in explants used for cell isolation, monolayer, self-assembled ITB spheroids, and spheroids seeded in polyglycolic acid (PGA) scaffolds. The protein expression profile of targets typically expressed by ligamentocytes (collagen types I–III, elastin, lubricin, decorin, aggrecan, fibronectin, tenascin C, CD44, β1-integrins, vimentin, F-actin, αSMA, and vascular endothelial growth factor A [VEGFA]) was compared between ITB and ACL fibroblasts. A donor- and age-dependent differing percentage of αSMA positive cells could be detected, which was similar in ITB and ACL tissues despite the grade of degeneration being significantly higher in the ACL due to harvesting them from OA knees. ITB fibroblasts survived for several months in an explant culture, continuously forming monolayers with VEGFA and an increased αSMA expression. They shared their expression profile with ACL fibroblasts. αSMA decreased during the monolayer to spheroid/scaffold transition. Using self-assembled spheroids, the migratory capacity of reversible myofibroblastic ITB cells can be utilized for colonizing biomaterials for ACL tissue engineering and to support ligament healing.

Highlights

The iliotibial band (ITB) or iliotibialis tract is a lateral thickening and reinforcement of the fascia of the thigh, starting at the superior iliac spine and passing over the lateral femoral epicondyle to attach to Gerdy’s tubercle on the anterolateral side of the tibial bone [1]
The fibroblasts resident in the extracellular matrix (ECM) of the ITB are responsible for the ECM synthesis but, due to their small overall number, represent only a low percentage of the total volume
It is known that anterior cruciate ligament (ACL) contain myofibroblasts expressing alpha smooth muscle actin [13]. αSMA-positive cells have been shown in the fascia lata [12]; the presence of myofibroblasts in ITB tissue is mainly unknown

Summary

Introduction

The iliotibial band (ITB) or iliotibialis tract is a lateral thickening and reinforcement of the fascia of the thigh (fascia lata), starting at the superior iliac spine and passing over the lateral femoral epicondyle to attach to Gerdy’s tubercle on the anterolateral side of the tibial bone [1]. Other typical ligament constituents have to be confirmed for the ITB Along this major longitudinal axis of the dense collagenous tissue, the fiber bundles show a slight undulating appearance in the ITB based on the biomechanical requirements of the fibrous tissue [2,3,5]. This robust ITB tissue is known to be a useful and easy-to-harvest autograft for ligament, tendon, and labrum reconstruction [5,8,9,10,11] and attracts increasing interest for various tissue engineering purposes. To gain more information on the myofibroblastic behaviour of ITB cells, we followed the αSMA expression in situ as well as during two-dimensional (2-D) and three-dimensional (3-D) cultures

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Discussion

Conclusion