Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (19): 2969-2975.doi: 10.3969/j.issn.2095-4344.3526

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Knee injury repair using human adipose-derived mesenchymal stem cells-based scaffold-free three-dimensional gel-like construct in pigs

Zhang Jianhui1, Ma Heran1, Tan Yi1, Wang Zhihui1, 2    

  1. 1Qilu Cell Therapy Technology Co., Ltd., Jinan 250000, Shandong Province, China; 2University Creative Research Initiatives Center of Shandong First Medical University, Jinan 250000, Shandong Province, China
  • Received:2020-04-23 Revised:2020-04-29 Accepted:2020-06-29 Online:2021-07-09 Published:2021-01-13
  • Contact: Wang Zhihui, PhD, Senior engineering, Qilu Cell Therapy Technology Co., Ltd., Jinan 250000, Shandong, China; University Creative Research Initiatives Center of Shandong First Medical University, Jinan 250000, Shandong Province, China
  • About author:Zhang Jianhui, Master, Qilu Cell Therapy Technology Co., Ltd., Jinan 250000, Shandong Province, China
  • Supported by:
    Shandong Taishan Industry Leading Talent Project, No. [2017]199 (to WZH)

Abstract: BACKGROUND: Compared with the traditional treatment methods, mesenchymal stem cells can fundamentally repair the damaged cartilage tissue, showing advantages in the repair of chondral defect. At present, there is no relevant research report on the ability of adipose-derived mesenchymal stem cells (ADMSCs)-based scaffold-free three-dimensional gel-like construct (ADMSCs-3D-GC) repairing chondral defect.
OBJECTIVE: To explore the feasibility of treating porcine chondral defect with ADMSCs-3D-GC.
METHODS:  Passage 3-5 of ADMSCs were cultured in the petri dish at a concentration of 4×105/cm2, with the MSCBM medium containing 5% serum substitute UltroGRO and 0.2 mmol/L ascorbic acid-2-phosphate. After stationary culture for 14 days, gently blow up the cells and cell matrix to form a three-dimensional adipose-derived mesenchymal stem cell gel. Osteogenesis, lipogenesis, and chondrogenesis were performed to identify the dryness of adipose mesenchymal stem cells in the gel. A cartilage lesion of 5 mm in diameter and 2 mm in depth was observed on the cartilage of the medial condyle of the femur in each knee of ten 4-month-old female Bama miniature pigs. The ADMSCs-3D-GC transplantation was performed at the damaged site of cartilage of the right knee joint to completely fill the defect and serve as the treatment group. The left side was not treated and served as the control group. After treatment for 4, 6 and 8 months, the cartilage and bone tissues were sampled and stained with hematoxyline and eosin, and Safranine O-Fast Green staining.
RESULTS AND CONCLUSION: The ADMSCs-3D-GC had dryness of mesenchymal stem cells, and could promote osteogenesis, lipogenesis and chondrogenesis. Cartilage tissue staining showed that the control group was significantly damaged. In the cell gel treatment group, a group of mature chondrocytes could be seen at the bottom of injury, and gradually transformed into immature chondrocytes, and residual granulation tissues were still visible at the superficial level. The effective rate was 62.5% (5/8) after 6-8 months of treatment. The results showed that ADMSCs-3D-GC could promote the repair of cartilage damage in pig knee joints.

Key words: stem cells, adipose-derived mesenchymal stem cells, adipose-derived mesenchymal stem cells-based scaffold-free three-dimensional gel-like construct, transplantation, knee, cartilage injury, Bama miniature pig

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