關節內注射間葉幹細胞於治療動物創傷性及退化性關節病之實證醫學研究與犬隻臨床應用之效用評估

蔡聲揚

doi:10.6342/NTU.2011.02536

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關節內注射間葉幹細胞於治療動物創傷性及退化性關節病之實證醫學研究與犬隻臨床應用之效用評估

Evidence-based study of intra-articular mesenchymal stem cell injection in animals with traumatic and degenerative arthropathies and evaluation of clinical therapeutic effects in dogs

蔡聲揚 , Masters　　Advisor：葉力森　　

繁體中文 DOI： 10.6342/NTU.2011.02536

間葉幹細胞；成體幹細胞；關節注射；骨關節炎；退化性關節病；實證醫學； mesenchymal stem cell ； adult stem cell ； intraarticular injection ； osteoarthritis ； degenerative joint disease ； evidence-based medicine

Abstract │ Reference (111) │ Altmetrics

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Osteoarthritis, also referred as degenerative joint disease(DJD), is a disease process associated with non-inflammatory, degenerative changes in the tissues of synovial joints and loss of articular cartilage, it is a common diagnosis in the clinic of aged population in both human and veterinary medicine. The poor regenerative capacity of cartilage and no available curative treatment options complicate satisfactory management of osteoarthritis.

Recently, stem cell therapy plays an important role in regenerative medicine due to its capacity to differentiate into new tissue to achieve proper tissue repair. Intra-articular injection of suspended stem cells, as a minimal invasive surgical option, could provide as an alternative therapy to osteoarthritis due to its effect of cartilage regeneration and immunomodulation mechanism, and therefore, stop or reverse the disease progression of osteoarthritis.

In chapter three, we systematically review the articles related to intra-articular mesenchymal stem cell injection in animals and consider them in the light of evidence-based (veterinary) medicine. A total of 11 studies from various animal species including rat、rabbit、porcine、goat、horse and dog were included. The study materials, evaluation methods and primary outcome of each study were analysed along with the evaluation of the study design and grading of the study quality by use of the FDA’s EBM scoring system. Evaluation of efficacy in published trials was hampered by the low number of studies and their heterogeneity nature, but most of individual study shows intra-articular stem cell injection could have positive therapeutic effect to a certain degree.

In chapter four, we use porcine adipose-derived mesenchymal stem cells as a stem cell source to treat canine osteoarthritis and evaluate its therapeutic effects. A total of 3 client-owned dogs with nature course of stifle degenerative joint disease were included in our study. We delivered approximately 5x106 stem cells per joint suspended in phosphate buffered saline via direct intra-articular injection. The outcome revealed that the score of doctor assessment, owner assessment, peak vertical force and vertical impulse of affect limb were functionally improved after intra-articular injection of mesenchymal stem cells.

Although some studies, whether in experimental animal models or in clinical trial, have provided promising results of intra-articular stem cell therapy in osteoarthritis, the information is still limited. The actual mechanism of stem cells participating in tissue repair, optimal number of cells needed to be injected, proper therapeutic protocols or the appropriate time point of intervention still remains to be discovered in the future.

Reference ( 111 ) 〈TOP〉

1. Abdel-Hamid M, and Hussein MR. Enhancement of the repair of meniscal wounds in the red-white zone (middle third) by the injection of bone marrow cells in canine animal model. Int J Exp Pathol 86: 117-123, 2005.
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2. Aigner T, Soder S, Gebhard PM, McAlinden A, and Haag J. Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis-structure, chaos and senescence. Nat Clin Pract Rheumatol 3: 391-399, 2007.
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3. Aoki KR. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 43: 9-15, 2003.
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4. Aragon CL, Hofmeister EH, and Budsberg SC. Systematic review of clinical trials of treatments for osteoarthritis in dogs. J Am Vet Med Assoc 230: 514-521, 2007.
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5. Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, Smith A, and Kadiyala S. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg 85: 1927, 2003.
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