Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (5): 668-672.doi: 10.3969/j.issn.2095-4344.1606

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Intra-articular injection of bone marrow mesenchymal stem cells combined with ligustrazine in a rabbit knee osteoarthritis model

Li Wei1, Xian Cheng2, Zhao Jinmin1, Lao Shan1   

  1. 1Department of Osteoarthrosis, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China; 2Langdong Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Revised:2018-11-15 Online:2019-02-18 Published:2019-02-18
  • Contact: Lao Shan, Chief physician, Department of Osteoarthrosis, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • About author:Li Wei, Master, Attending physician, Department of Osteoarthrosis, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Supported by:

    the Self-Financing Project of Traditional Chinese Medicine, No. GZZC15-33 (to LW); the Youth Foundation of Guangxi Medical University, No. GXMUYSF201618 (to LW)

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Abstract:

BACKGROUND: Mesenchymal stem cells or ligustrazine alone has limited efficacy in the treatment of osteoarthritis. Whether bone marrow mesenchymal stem cell transplantation combined with ligustrazine can achieve better results has yet to be reported.
OBJECTIVE: To define whether ligustrazine has the function to promote the chondrogenic differentiation and regeneration of bone marrow mesenchymal stem cells.
METHODS: Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits (1 week old, provided by the Animal Experimental Center of Guangxi Medical University in China) and cultured to the third generation. Forty healthy New Zealand white rabbits (5-6 months old, provided by the Animal Experimental Center of Guangxi Medical University) were randomly divided into four groups (n=10 per group). Except for the blank control group, models of knee osteoarthritis were made in the right hind limbs of rabbits in the extension position using the plaster fixation method in the other three groups. On the 2nd day after the successful modeling, the rabbits in the blank control group were injected with 0.3 mL of normal saline once a week for 4 weeks. In the pure ligustrazine group, the rabbit knee joint cavity was injected with 0.3 mL of ligustrazine once a week for 4 weeks. In the cell transplantation group, the rabbit knee joint cavity was injected with one-off bone marrow mesenchymal stem cells (0.3 mL, 3×108 cells/L), and the knee joint was injected with 0.3 mL of normal saline once a week for 4 weeks. In the combination group, one-off bone marrow mesenchymal stem cells (0.3 mL, 3×108 cells/L) were injected into the rabbit knee joint, while intra-articular injection of ligustrazine, 0.3 mL, once a week, for 4 weeks, were simultaneously performed. The knee joint fluid of each group was collected at 6 and 12 weeks after the intervention.
RESULTS AND CONCLUSION: (1) The knee joint cartilage of the blank control group had no obvious wear as well as no obvious hyperplasia and inflammatory changes in the surrounding synovial membrane. The knee joint of the ligustrazine group was seriously worn, and the cartilage damage was defined as grade 3, but the subchondral bone was not exposed, accompanied with obvious surrounding synovial hyperplasia. In the cell transplantation and combination groups, the knee joint was slightly worn, the cartilage damage was confirmed as grade 1 or 2, and the surrounding synovial hyperplasia and inflammatory changes were not obvious. We could not distinguish the severity of wear between the cell transplantation and combination groups under the general view. (2) Compared with the cell transplantation group, the levels of interleukin-1β and interleukin-6 in the knee joint fluid of rabbits were significantly lower in the ligustrazine group and combination group (P < 0.05). At the 6th week, when the cartilage destruction was not obvious in the early stage of rabbit knee osteoarthritis, the levels of inflammatory factors in the knee joint fluid were the lowest in the ligustrazine group. At the 12th week, the levels of inflammatory factors in the joint fluid were the lowest in the combination group. To conclude, ligustrazine cannot obviously promote the chondrogenic differentiation and regeneration of bone marrow mesenchymal stem cells, but it can significantly reduce the level of inflammatory factors and relieve clinical symptoms in patients with knee osteoarthritis.


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Osteoarthritis, Knee, Bone Marrow, Mesenchymal Stem Cells, Drugs, Chinese Herbal, Tissue Engineering

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