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

2016 Fiscal Year Final Research Report

• 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
• Keywords: MPS II / 骨髄移植 / キメリズム

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.

Free Research Field

小児科学