Tissue Eng Regen Med.  2020 Jun;17(3):313-322. 10.1007/s13770-020-00256-6.

A Combinational Therapy of Articular Cartilage Defects: Rapid and Effective Regeneration by Using Low-Intensity Focused Ultrasound After Adipose Tissue-Derived Stem Cell Transplantation

Affiliations
  • 1Department of Medical Sciences, College of Medicine, Catholic Kwandong University, 24, Beomil-ro 579beon-gil, Gangneung-si, Gangwon-do 25601, Republic of Korea
  • 2International St. Mary’s Hospital, Catholic Kwandong University, 25, Simgok-ro 100beon-gil, Seo-gu, Incheon 22711, Republic of Korea
  • 3Institute for Biomedical Convergence, College of Medicine, Catholic Kwandong University, 24, Beomil-ro 579beon-gil, Gangneung-si, Gangwon-do 25601, Republic of Korea
  • 4Department of Orthopedic Surgery, International St. Mary’s Hospital, College of Medicine, Catholic Kwandong University, 25, Simgok-ro 100beon-gil, Seo-gu, Incheon 22711, Republic of Korea

Abstract

BACKGROUND
Although low-intensity pulsed ultrasound has been reported to be potential cartilage regeneration, there still unresolved treatment due to cartilage fibrosis and degeneration by a lack of rapid and high-efficiency treatment. The purpose of this study was to investigate the effect of a combination therapy of focused acoustic force and stem cells at site for fast and efficient healing on cartilage regeneration.
METHODS
Using a rat articular cartilage defects model, one million adipose tissue-derived stem cells (ASCs) were injected into the defect site, and low-intensity focused ultrasound (LOFUS) in the range of 100–600 mV was used for 20 min/day for 2 weeks. All experimental groups were sacrificed after 4 weeks in total. The gross appearance score and hematoxylin and eosin (H&E), Alcian blue, and Safranin O staining were used for measuring the chondrogenic potential. The cartilage characteristics were observed, and type II collagen, Sox 9, aggrecan, and type X collagen were stained with immunofluorescence. The results of the comprehensive analysis were calculated using the Mankin scoring method.
RESULTS
The gross appearance scores of regenerated cartilage and chondrocyte-like cells in H&E images were higher in LOFUS-treated groups compared to those in negative control or ASC-treated groups. Safranin O and Alcian blue staining demonstrated that the 100 and 300 mV LOFUS groups showed greater synthesis of glycosaminoglycan and proteoglycan. The ASC ? LOFUS 300 mV group showed positive regulation of type II collagen, Sox 9 and aggrecan and negative regulation of type X collagen, which indicated the occurrence of cartilage regeneration based on the Mankin score result.
CONCLUSION
The combination therapy, which involved treatment with ASC and 300 mV LOFUS, quickly and effectively reduced articular cartilage defects.

Keyword

Low-intensity focused ultrasound; Adipose tissue-derived stem cell; Articular cartilage defect; Regeneration
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