A comparative study of the epiligament of the medial collateral and anterior cruciate ligaments in the human knee: Immunohistochemical analysis of CD 34, α-smooth muscle actin and vascular endothelial growth factor in relation to epiligament theory

Георгиев, Г.; Tubbs, R. Shane; Olewnik, Łukasz; Zielinska, Nicol; Telang, Manasi; Ananiev, Julian; Dimitrova, Iva N.; Slavchev, Svetoslav A.; Yordanov, Yordan; LaPrade, Robert F.; Ruzik, Kacper; Landzhov, Boycho

doi:10.1016/j.knee.2022.07.013

Cited by 4 publications

(12 citation statements)

References 54 publications

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“…The EL in the MCL midpart is involved in fostering enhanced healing potential. The MCL proximal and distal parts have worse healing capacity regarding CD34 expression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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Are There Any Differences in the Healing Capacity between the Medial Collateral Ligament’s (MCL) Proximal and Distal Parts in the Human Knee? Quantitative and Immunohistochemical Analysis of CD34, α-Smooth Muscle Actin (α-SMA), and Vascular Endothelial Growth Factor (VEGF) Expression Regarding the Epiligament (EL) Theory

Georgiev,

Yordanov,

Gaydarski

et al. 2024

Biomedicines

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The human knee is a complex joint that comprises several ligaments, including the medial collateral ligament (MCL). The MCL provides stability to the knee and helps prevent its excessive inward movement. The MCL also has a thin layer of connective tissue known as the epiligament (EL), which adheres to the ligament. This unique feature has drawn attention in the field of ligament healing research, as it may have implications for the recovery process of MCL injuries. According to the EL theory, ligament regeneration relies heavily on the provision of cells, blood vessels, and molecules. The present study sought to compare the expression of vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in healthy knees’ proximal and distal MCL segments to better understand how these proteins affect ligament healing. By improving the EL theory, the current results could lead to more effective treatments for ligament injury. To conduct the present analysis, monoclonal antibodies were used against CD34, α-SMA, and VEGF to examine samples from 12 fresh knee joints’ midsubstance MCLs. We identified a higher cell density in the EL than in the ligament connective tissue, with higher cell counts in the distal than in the proximal EL part. CD34 immunostaining was weak or absent in blood vessels and the EL, while α-SMA immunostaining was strongest in smooth muscle cells and the EL superficial layer. VEGF expression was mainly in the blood vessels’ tunica media. The distal part showed more SMA-positive microscopy fields and higher cell density than the proximal part (4735 vs. 2680 cells/mm2). Our study identified CD34, α-SMA, and VEGF expression in the MCL EL, highlighting their critical role in ligament healing. Differences in α-SMA expression and cell numbers between the ligament’s proximal and distal parts may explain different healing capacities, supporting the validity of the EL theory in ligament recovery.

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“…The EL in the MCL midpart is involved in fostering enhanced healing potential. The MCL proximal and distal parts have worse healing capacity regarding CD34 expression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…The collected samples were then subjected to further analysis. Samples were taken from the ligament’s proximal and distal thirds and underwent a standard fixation procedure [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Are There Any Differences in the Healing Capacity between the Medial Collateral Ligament’s (MCL) Proximal and Distal Parts in the Human Knee? Quantitative and Immunohistochemical Analysis of CD34, α-Smooth Muscle Actin (α-SMA), and Vascular Endothelial Growth Factor (VEGF) Expression Regarding the Epiligament (EL) Theory

Georgiev,

Yordanov,

Gaydarski

et al. 2024

Biomedicines

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“…Samples were acquired from the proximal and distal parts of the ACL and fixed according to the established protocol for routine histological and immunohistochemical examination, described in detail in our previous study [12].…”

Section: Tissue Preparationmentioning

confidence: 99%

“…For light microscopy, 5 µm thick sections were cut on a microtome (Leica, Wetzlar, Germany). The paraffin sections were mounted on microscope slides and routinely stained with Mallory's trichrome stain and hematoxylin and eosin according to the standard methods described in our previous studies [11,12].…”

Section: Light Microscopymentioning

confidence: 99%

“…While noting similar morphological characteristics of the EL in both ligaments, they identified a significant difference in cell quantity, with the MCL exhibiting a higher cell count, potentially explaining its superior healing capacity [11]. Exploring the morphological features of the EL and recognizing significant differences in cell and molecule numbers responsible for healing (including major collagen types, matrix metalloproteinases, fibronectin, CD34, VEGF, α-SMA), the EL theory was further refined, providing insights into the challenges of ACL healing in the midsubstance [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Do the Differences in the Epiligament of the Proximal and Distal Parts of the Anterior Cruciate Ligament Explain Their Different Healing Capacities? Quantitative and Immunohistochemical Analysis of CD34 and α-SMA Expression in Relation to the Epiligament Theory

Georgiev,

Yordanov,

Olewnik

et al. 2024

Biomedicines

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The aim of this study was to assess the epiligament theory by determining the normal epiligament morphology of the proximal and distal parts of the anterior cruciate ligament in humans and analyzing the differences between them and the midportion of the ligament in terms of cell numbers and expression of CD34 and α-SMA. Samples were obtained from the anterior cruciate ligaments of 12 fresh knee joints. Monoclonal antibodies against CD34 and α-SMA were used for immunohistochemistry. Photomicrographs were analyzed using ImageJ software, version 1.53f. The cell density was higher in the epiligament than in the ligament connective tissue. Cell counts were higher in the proximal and distal thirds than in the midsubstance of the epiligament. CD34 was expressed similarly in the proximal and distal thirds, although it seemed slightly more pronounced in the distal third. α-SMA expression was more robust in the proximal than the distal part. The results revealed that CD34 and α-SMA are expressed in the human epiligament. The differences between the numbers of cells in the proximal and distal parts of the epiligament and the expression of CD34 and α-SMA enhance epiligament theory. Future investigations into improving the quality of ligament healing should not overlook the epiligament theory.

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New insight into the morphological characteristics of patella cubiti

et al. 2023

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A comparative study of the epiligament of the medial collateral and anterior cruciate ligaments in the human knee: Immunohistochemical analysis of CD 34, α-smooth muscle actin and vascular endothelial growth factor in relation to epiligament theory

Cited by 4 publications

References 54 publications

Do the Differences in the Epiligament of the Proximal and Distal Parts of the Anterior Cruciate Ligament Explain Their Different Healing Capacities? Quantitative and Immunohistochemical Analysis of CD34 and α-SMA Expression in Relation to the Epiligament Theory

New insight into the morphological characteristics of patella cubiti

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