Identification of endogenous stem cells of the intervertebral disc in degeneration and treatment applications

• Project/Area Number: 20791056
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Tokai University
• Principal Investigator: SAKAI Daisuke Tokai University, 医学部, 講師 (10408007)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 整形外科学 / 脊椎脊髄病学 / 椎間板 / 再生医療 / 幹細胞 / 脊椎 / 髄核細胞 / ニッチ / 椎間板変性 / 脊椎外科 / 前駆細胞 / 再生医学

Research Abstract

Heterogeneity of nucleus pulposus cells was revealed in various animal species including human. Endogenous stem/progenitor cells were identified in the intervertebral disc tissue. Its immaturity correlated negatively with age in humans showing that number of endogenous stem cell populations in the inetervertebral disc decrease with aging. Exogenous stem cells did not supply cells to the degenerated intervertebral disc showing that in the inetervertebral disc, exogenous mobilization of cells is extremely difficult. These facts rationalize the idea of supplying cells through external access.

Research Products

• [Journal Article] Variations in gene and protein expression in human nucleus pulposus in comparisonwith annulus fibrosus and cartilage cells: potential associations with aging and degeneration. (2010)
  • Author(s): Rutges J, Creemers LB, Dhert W, Milz S, Sakai D, Mochida J, Alini M, Grad S
  • Journal Title: Osteoarthritis Cartilage. 18(3) Pages: 416-423
  • Peer Reviewed
• [Journal Article] Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation. (2010)
  • Author(s): Murai K, Sakai D, Nakamura Y, Nakai T, Igarashi T, Seo N, Murakami T, Kobayashi E, Mochida J
  • Journal Title: Eur Cell Mater. 19 Pages: 13-21
  • Peer Reviewed
• [Journal Article] Variations in gene and protein expression in human nucleus pulposus in comparison with annulus fibrosus and cartilage cells : potential associations with (2010)
  • Author(s): Rutges, Jun
  • Journal Title: Osteoarthritis Cartilage 18 Pages: 416-23
  • Peer Reviewed
• [Journal Article] Differential phenotype of intervertebral disc cells: microarray and immunohistochemical analysis of canine nucleus pulposus and anulus fibrosus. (2009)
  • Author(s): Sakai D, Nakai T, Mochida J, Alini M, Grad S
  • Journal Title: Spine 34(14) Pages: 1448-1456
  • NAID: 10027244193
  • Peer Reviewed
• [Journal Article] Activation of TonEBP by calcium controls {beta}1, 3-glucuronosyltransferase-I expression, a key regulator of glycosaminoglycan synthesis in cells of the intervertebral disc. (2009)
  • Author(s): Hiyama A, Gajghate S, Sakai D, Mochida J, Shapiro IM, Risbud MV
  • Journal Title: J Biol Chem. 284(15) Pages: 9824-9834
  • Peer Reviewed
• [Journal Article] Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor-related genes in human nucleus pulposus cell line. (2009)
  • Author(s): Kobayashi Y, Sakai D, Iwashina T, Iwabuchi S, Mochida J
  • Journal Title: Eur Cell Mater. 17 Pages: 15-22
  • Peer Reviewed
• [Journal Article] Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus pulposus cells of the intervertebral disc. (2009)
  • Author(s): Gajghate S, Hiyama A, Shah M, Sakai D, Anderson DG, Shapiro IM, Risbud MV
  • Journal Title: Bone Miner Res. 24(6) Pages: 992-1001
  • Peer Reviewed
• [Journal Article] Differential phenotype of intervertebral disc cells : microarray and immunohistochemical analysis of canine nucleus pulposus and anulus fibrosus (2009)
  • Author(s): Sakai, Daisuke
  • Journal Title: Spine 34 Pages: 1448-56
  • NAID: 10027244193
  • Peer Reviewed
• [Journal Article] Activation of TonEBP by calcium controls {beta}1,3-glucuronosyltransferase-I expression, a key regulator of glycosaminoglycan synthesis in cells of the intervertebral disc (2009)
  • Author(s): Hiyama, Akihiko
  • Journal Title: Journal of Biological Chemistry 284 Pages: 9824-34
  • Peer Reviewed
• [Journal Article] Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus nuluosus cells of the intervertebral disc (2009)
  • Author(s): Gajghate, Sachin
  • Journal Title: Journal of Bone and Mineral Research 24 Pages: 992-1001
  • Peer Reviewed
• [Journal Article] Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor-related genes in human nucleus pulposus cell line (2009)
  • Author(s): Kobayashi, Yuka
  • Journal Title: European Cells and Materials 17 Pages: 15-22
  • Peer Reviewed
• [Journal Article] Primary immune system responders to nucleus pulposus cells : evidence for immune response in disc herniation (2009)
  • Author(s): Murai, Kunihiko
  • Journal Title: European Cells and Materials 19 Pages: 13-21
  • Peer Reviewed
• [Journal Article] Future perspectives of cell-based therapy for intervertebral disc disease (2008)
  • Author(s): Sakai, Daisuke
  • Journal Title: European Spine Journal 17 Pages: 452-8
  • Peer Reviewed
• [Journal Article] Synergistic role of c-Myc and ERK1/2 in the mitogenic response to TGFbeta-1 in cultured rat nucleus nulnosus cells (2008)
  • Author(s): Nakai, Tomoko
  • Journal Title: Arthritis Research and Therapy 10
  • Peer Reviewed
• [Journal Article] Stem cell annlications in intervertebral disc renair (2008)
  • Author(s): Hiyama, Akihiko
  • Journal Title: Cellular and Molecular Biology 54 Pages: 24-32
  • Peer Reviewed
• [Journal Article] Age-related effects of cocultured rat nucleus pulposus cells a nd macrophages on nitric oxide production and cytokine imbalance (2008)
  • Author(s): Katsuno, Raijiro
  • Journal Title: Snine 33 Pages: 845-9
  • Peer Reviewed
• [Journal Article] Cross talk between Smad transcription factors and TNF-alpha in intervertebral disc degeneration (2008)
  • Author(s): Hiyama, Akihiko
  • Journal Title: Biochemical Biophysical Research Communications 369 Pages: 679-85
  • Peer Reviewed
• [Journal Article] Low-intensity pulsed ultrasound stimulation enhances TIMP-1 in nucleus pulposus cells and MCP-1 in macrophages in the rat (2008)
  • Author(s): Omi, Hiroko
  • Journal Title: Journal of Orthopaedic Research 6 Pages: 865-71
  • Peer Reviewed
• [Journal Article] Transplantation of mesenchymal stem cells in a canine disc degeneration model (2008)
  • Author(s): Hiyama, Akihiko
  • Journal Title: Journal of Orthopaedic Research 5 Pages: 589-600
  • Peer Reviewed
• [Presentation] 細胞レベルからの椎間板再生-細胞移植療法のその先に- (2008)
  • Author(s): 酒井大輔
  • Organizer: 第19回日本腰痛学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-01
• [Patent(Industrial Property Rights)] 椎間板髄核幹/前駆細胞、その作成方法および用途 (2010)
  • Inventor(s): 酒井大輔、持田讓治、安藤潔、中村嘉彦
  • Industrial Property Rights Holder: 学校法人東海大学
  • Filing Date: 2010-03-30