Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II

• Project/Area Number: 25860884
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Yokoi Kentaro 東京慈恵会医科大学, 医学部, 助教 (20459655)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: MPS II / 骨髄移植 / キメリズム / ムコ多糖症ＩＩ型 / 移植後キメラ / ハンター症候群 / キメラ / 先天性代謝異常症 / ムコ多糖症II型

Outline of Final Research Achievements

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficient activity of the iduronate-2-sulfatase. This leads to accumulation of glycosaminoglycans (GAGs) in the lysosomes of various cells. Although it has been proposed that bone marrow transplantation (BMT) may have a beneficial effect for patients with MPS II, the requirement for donor cell chimerism to reduce GAG levels is unknown. We transplanted various ratios of normal and MPS II bone marrow cells in a mouse model of MPS II and analyzed GAG accumulation in various tissues. Chimerism of whole leukocytes and each lineage of BMT recipients’ peripheral blood were similar to the infusion ratios. GAGs were significantly reduced in the liver, spleen and heart of recipients. The level of reduction of GAGs in these tissues depends on the percentage of normal cell chimerism. In contrast to these tissues, a reduction in GAGs was not observed in the kidney and brain even if 100% donor chimerism was achieved.

Research Products

• [Journal Article] Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II (2015)
  • Author(s): Yokoi K, Akiyama K, Kaneshiro E, Higuchi T, Shimada Y, Kobayashi H, Akiyama M, Otsu M, Nakauchi H, Ohashi T, Ida H
  • Journal Title: Journal of inherited metabolic disease Volume: 38 Issue: 2 Pages: 333-40
  • DOI: 10.1007/s10545-014-9800-x
  • Peer Reviewed
• [Presentation] Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II (2014)
  • Author(s): 横井健太郎、秋山和政、金城栄子、樋口孝、嶋田洋太、小林博司、秋山政晴、大津真、中内啓光、大橋十也、井田博幸
  • Organizer: 第56回日本小児血液・がん学会学術集会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II (2014)
  • Author(s): 横井健太郎、秋山和政、金城栄子、樋口孝、嶋田洋太、小林博司、秋山政晴、大津真、中内啓光、大橋十也、井田博幸
  • Organizer: 第56回日本先天代謝異常学会総会
  • Place of Presentation: 江陽グランドホテル（仙台）
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] MPSⅡ型マウスの骨髄移植における、必要最低骨髄細胞生着率の検討 (2014)
  • Author(s): 横井健太郎、秋山和政、金城栄子、樋口孝、嶋田洋太、小林博司、秋山政晴、大津真、中内啓光、大橋十也、井田博幸
  • Organizer: 第117回日本小児科学会学術集会
  • Place of Presentation: （名古屋）
  • Year and Date: 2014-04-11 – 2014-04-13
• [Presentation] MPSII型の骨髄移植における必要最低骨髄細胞生着率の検討 (2014)
  • Author(s): 横井健太郎
  • Organizer: 第117回日本小児科学会学術集会
  • Place of Presentation: 名古屋国際会議場