Int J Stem Cells.  2019 Mar;12(1):162-169. 10.15283/ijsc18022.

Mesenchymal Stem Cells Decrease Tunnel Widening of Anterior Cruciate Ligament Reconstruction in Rabbit Model

• Hur CI
• Ahn HW
• Seon JK
• Song EK
• Kim GE

• KMID: 2447234
• DOI: http://doi.org/10.15283/ijsc18022

Abstract

BACKGROUND AND OBJECTIVES
The study investigated the effect of mesenchymal stem cells (MSCs) or fibrin glue on tunnel widening after anterior cruciate ligament (ACL) reconstruction compared with biologic free control without any biologic agents in the rabbit model.
METHODS AND RESULTS
ACL reconstructions were performed in 18 New Zealand white rabbits. All animals were divided into 3 groups according to the following reconstruction conditions and euthanized 12 weeks postoperatively for radiologic and histologic analyses. Thirty-two knees (control group=10; fibrin group=11; MSCs group=11) were finally evaluated. On micro-CT scan, mean femoral tunnel widening on oblique-sagittal image was 0.7±0.4 mm in the control group, 0.22±0.1 mm in the fibrin group and 0.25±0.1 mm in the MSCs group (p=0.001). Fibrin group and MSCs group showed significant differences compared with control group (p=0.002, 0.002). Mean tibial tunnel widening on oblique-sagittal image was 0.76±0.5 mm, 0.27±0.1 mm and 0.29±0.2 mm in the control, fibrin and MSCs group. Fibrin and MSCs group showed significant differences compared with control group (p=0.017, 0.014). Hounsfield Units (HU) were not significantly different between 3 groups (p>0.05). Histological analysis revealed that the architecture of graft in the MSCs group featured hypercellularity and compact collagen deposit.
CONCLUSION
ACL reconstruction using MSCs seemed decrease tunnel widening in rabbit model. Further study with large animals is required to confirm efficacy on decreasing tunnel widening.

Keyword

Anterior cruciate ligament; Mesenchymal stem cell; Tunnel widening; Rabbit model

MeSH Terms

Animals
Anterior Cruciate Ligament Reconstruction*
Anterior Cruciate Ligament*
Biological Factors
Collagen
Fibrin
Fibrin Tissue Adhesive
Knee
Mesenchymal Stromal Cells*
Rabbits
Transplants
Biological Factors
Collagen
Fibrin
Fibrin Tissue Adhesive

Figure

• 

  Fig. 1 Surgical process of ACL reconstruction in rabbit model. (A) The native ACL and extensor digitorum longus were identified after medial para-patellar arthrotomy. (B) The EDL tendon with 2 mm diameter and 25 mm length was harvested. (C, D) Femoral and Tibial tunnel were made using 2 mm drill at footprints of native ACL. (E) The harvested tendon was passed through the femoral and tibial tunnel and (F) was tethered with suture to the screw inserted into the bone.

• 

  Fig. 2 CT image measuring tunnel widening and Hounsfield units (HUs). The tunnel diameter (white arrow) were calculated on the oblique-coronal (A) and oblique-sagittal image (B) 2 mm distal from the femoral and tibial articular surface. On the same distance from articular surface, HUs were measured in regions of interest (1.5 mm×1.5 mm squared) in the tunnel (white square) and the cancellous bone around the tunnel (black square).

• 

  Fig. 3 (A) Gross photo and (B) oblique-sagittal section appearance showing reconstruced ACL on knee joint of rabbit.

• 

  Fig. 4 Photomicrographs of H & E staining in 12-week ACL reconstruction. In the control group (A, D), the smooth tendon-bone integration (firm attachment fo the graft to the bone) were observed. However, hypocellularity and less compacted collagen fiber was observed. In fibrin group (B, E), although partial tear of the graft has been shown, there are good cellularity and more compact collagen fiber. In the MSCs groups (C, F), the good architecture with hypercellularity and compacted collagen deposit was shown in compared with other groups.

Reference

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