臨床整形外科57巻11号

2022年11月発行

特集 腰椎椎間板ヘルニアのCutting Edge

椎間板再生医療の実用化に向けた超高純度な生体吸収性バイオマテリアルと同種骨髄由来間葉系幹細胞の開発

著者： 須藤英毅¹

所属機関： ¹北海道大学大学院医学研究院整形外科学教室脊椎・脊髄先端医学分野

ページ範囲：P.1313 - P.1318

椎間板は無血管野であり栄養供給に乏しく細胞分裂能が低いため，変性あるいは欠損した椎間板は自然再生しない．組織再生を目指して幹細胞を単純移植しても周囲組織との相互作用がなく十分な生着が期待できないため，超高純度な硬化性ゲルを開発し腰椎椎間板ヘルニアに対する探索的医師主導治験を実施してきた．一方，中高年期の自己修復能の乏しい患者へのバイオマテリアル単独治療には限界があり，混合性腰部脊柱管狭窄症に対しては，硬化性ゲルに他家骨髄由来間葉系幹細胞を組み合わせた細胞治療法による医師主導治験を行っている．

参考文献

1) Sudo H, Oda I, Abumi K, et al. In vitro biomechanical effects of reconstruction on adjacent motion segment:comparison of aligned/kyphotic posterolateral fusion with aligned posterior lumbar interbody fusion/posterolateral fusion. J Neurosurg 2003;99(2 Suppl):221-8.

2) Sudo H, Oda I, Abumi K, et al. Biomechanical study on the effect of five different lumbar reconstruction techniques on adjacent level intradiscal pressure and lamina strain. J Neurosurg Spine 2006;5(2):150-5.

3) Yamada K, Sudo H, Iwasaki K, et al. Caspase 3 silencing inhibits biomechanical overload-induced intervertebral disc degeneration. Am J Pathol 2014;184(3):753-64.

4) Sudo H, Minami A. Regulation of apoptosis in nucleus pulposus cells by optimized exogenous Bcl-2 overexpression. J Orthop Res 2010;28(12):1608-13.

5) Sudo H, Minami A. Caspase 3 as a therapeutic target for regulation of intervertebral disc degeneration in rabbits. Arthritis Rheum 2011;63(6):1648-57.

6) Sudo H, Yamada K, Iwasaki K, et al. Global identification of genes related to nutrient deficiency in intervertebral disc cells in an experimental nutrient deprivation model. PLoS One 2013;8(3):e58806. doi:10.1371/journal.

7) Arnoldi CC, Brodsky AE, Cauchoix J, et al. Lumbar spinal stenosis and nerve root entrapment syndromes. Definition and classification. Clin Orthop Relat Res 1976;(115):4-5.

8) Tsujimoto T, Sudo H, Todoh M, et al. An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair:A preclinical proof-of-concept study. EBioMedicine 2018;37:521-34.

9) Ura K, Yamada K, Tsujimoto T, et al. Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy. Sci Rep 2021;11(1):638. doi:10.1038/s41598-020-79958-9.

10) Yamada K, Maeda K, Ito YM, et al. Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation:Study protocol for a first-in-human pilot study. Contemp Clin Trials Commun 2021;23:100805. doi:10.1016/j.conctc.2021.100805.

11) Ukeba D, Sudo H, Tsujimoto T, et al. Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs. EBioMedicine 2020;53:102698. doi:10.1016/j.ebiom.2020.102698.

12) Ukeba D, Yamada K, Tsujimoto T, et al. Bone marrow aspirate concentrate combined with in situ forming bioresorbable gel enhances intervertebral disc regeneration in rabbits. J Bone Joint Surg Am 2021;103(8):e31. doi:10.2016/JBJS.20.00606.

13) Mabuchi Y, Morikawa S, Harada S, et al. LNGFR(+)THY-1(+)VCAM-1(hi+) cells reveal functionally distinct subpopulations in mesenchymal stem cells. Stem Cell Reports 2013;1(2):152-65.

14) Houlihan DD, Mabuchi Y, Morikawa S, et al. Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-α. Nat Protoc 2012;7(12):2103-11.

15) Ukeba D, Yamada K, Suyama T, et al. Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration. EBioMedicine 2022;76:103845. doi:10.1016/j.ebiom.2022.103845.