臨床整形外科53巻1号

2018年01月発行

誌上シンポジウム 脂肪幹細胞と運動器再生

脂肪組織由来間葉系幹細胞の三次元構造体による骨軟骨再生

著者： 村田大紀¹² 中山功一²

所属機関： ¹鹿児島大学共同獣医学部臨床獣医学講座外科学分野 ²佐賀大学医学部臓器再生医工学研究室

ページ範囲：P.35 - P.41

　ブタの頚部から採取した脂肪組織から，間葉系幹細胞(AT-MSCs)を分離培養した．その後，AT-MSCsのみで細胞凝集塊を作製した後に，細胞の足場材料を用いることなく鋳型を使用して三次元構造体(プラグ)を作製した．大腿骨滑車溝に円柱状の骨軟骨欠損孔を2つ作製し，一方にはプラグを移植し(移植孔)，もう一方は非移植とした(対照孔)．組織学的評価は手術後6カ月および12カ月に行った．その結果，対照孔では，骨軟骨組織の修復が部分的に認められたものの不完全であった．それに対して，手術後6カ月の移植孔では，欠損部の表層には軟骨組織が再生されており，深層には軟骨下骨が形成されていた．さらに，手術後12カ月の移植孔では，軟骨組織が正常軟骨とほぼ同様の厚さで再生されていた．

参考文献

1) Muraki S, Oka H, Akune T, et al. Prevalence of radiographic knee osteoarthritis and its association with knee pain in the elderly of Japanese population-based cohorts:The ROAD study. Osteoarthritis Cartilage 2009;17:1137-43.

2) Mankin HJ. The response of articular cartilage to mechanical injury. J Bone Joint Surg Am 1982;64:460-6.

3) Lane JG, Massie JB, Ball ST. Follow-up of osteochondral plug transfers in a goat model:a 6-month study. Am J Sports Med 2004;32:1440-50.

4) Tatebe M, Nakamura R, Kagami H, et al. Differentiation of transplanted mesenchymal stem cells in a large osteochondral defect in rabbit. Cytotherapy 2005;7:520-30.

5) Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.

6) Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Bio Cell 2002;13:4279-95.

7) Nimura A, Muneta T, Koga H, et al. Increased proliferation of human synovial mesenchymal stem cells with autologous human serum:Comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis Rheum 2008;58:501-10.

8) Jones EA, Crawford A, English A, et al. Synovial fluid mesenchymal stem cells in health and early osteoarthritis:detection and functional evaluation at the single-cell level. Arthritis Rheum 2008;58:1731-40.

9) Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells:candidate MSC-like cells from umbilical cord. Stem Cells 2003;21:105-10.

10) Erices AA, Allers CI, Conget PA, et al. Human cord blood-derived mesenchymal stem cells home and survive in the marrow of immunodeficient mice after systemic infusion. Cell Transplant 2003;12:555-61.

11) Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue:implications for cell-based therapies. Tissue Eng 2001;7:211-28.

12) De Ugarte DA, Morizono K, Elbarbary A. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 2003;174:101-9.

13) Cukierman E, Pankov R, Stevens DR, et al. Taking cell-matrix adhesions to the third dimension. Science 2001;294:1708-12.

14) Baraniak PR, McDevitt TC. Scaffold-free culture of mesenchymal stem cell spheroids in suspension preserves multilineage potential. Cell Tissue Res 2012;347:701-11.

15) Rettinger CL, Fourcaudot AB, Hong SJ, et al. In vitro characterization of scaffold-free three-dimensional mesenchymal stem cell aggregates. Cell Tissue Res 2014;358:395-405.

16) Ishihara K, Nakayama K, Akieda S, et al. Simultaneous regeneration of full-thickness cartilage and subchondral bone defects in vivo using a three-dimensional scaffold-free autologous construct derived from high-density bone marrow-derived mesenchymal stem cells. J Orthop Surg Res 2014;9:98.

17) Murata D, Tokunaga S, Tamura T, et al. A preliminary study of osteochondral regeneration using a scaffold-free three-dimensional construct of porcine adipose tissue-derived mesenchymal stem cells. J Orthop Surg Res 2015;10:35.

18) Nakayama K. In vitro biofabrication of tissues and organs. In:Forgacs G, Sun W (ed). Biofabrication:Micro- and Nano-Fabrication, Printing, Patterning and Assemblies. Oxford:William Andrew;2013:p1-21.

19) Fraser JK, Fraser JK, Hicok KC, et al. The Celution®System:Automated processing of adipose-derived regenerative cells in a functionally closed system. Adv Wound Care (New Rochelle) 2014;3:38-45.

20) Wang YX, Griffith JF, Ahuja AT. Non-invasive MRI assessment of the articular cartilage in clinical studies and experimental settings. World J Radiol 2010;2:44-54.

21) Hani AF, Kumar D, Malik AS, et al. Non-invasive and in vivo assessment of osteoarthritic articular cartilage:a review on MRI investigations. Rheumatol Int 2015;35:1-16.