2005 Fiscal Year Final Research Report Summary
THE STUDY OF RECONSTITUTION OF RENAL CELLS BY BONE MARROW STEM CELLS AND THE POTENTIAL FOR REGENERATIVE MEDICINE IN THE THERAPY OF RENAL DISEASE.
| Project/Area Number |
14571040
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
UTSUNOMIYA Yasunori THE JIKEI UNIVERSITY SCHOOL OF MEDICINE, THE MEDICAL DEPARTMENT, LECTURER, 医学部, 講師 (70231181)
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| Project Period (FY) |
2002 – 2005
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| Keywords | bone marrow cells / mesangial cells / bone marrow trasnplantation / diabetic nephropathy / progenitor cells / tissue repair / renal injury / メサンギウム細胞 |
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| Research Abstract |
1.The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells.
To investigate whether bone marrow cells (BMC) may have the potential of differentiation to glomerular cells, we transplanted BMC from mice transgenic for green fluorescence protein (GFP) into syngeneic C57BL/6j (B6) mice. In this study, GFP^+ cells were clearly visible in the glomeruli, the periglomerular space, and the interstitium of [GFP→B6]mice 4 week after bone marrow transplantation (BMT). However, [B6→B6]mice exhibited no GFP^+cells in glomeruli at any observation time. In immunohistochemical analysis, F4/80^+macrophages and Thy-1^+ cells were barely observed in glomeruli of [GFP→B6]mice at 24 wk after BMT. In addition, only 5% of GFP^+ cells were positive for macrophage scavenger receptors. Then, we isolated glomeruli from [GFP→B6]mice at 24 wk after BMT. In immunofluorescence assays, the majority of cultured cells stained for desmin and about 60% of desmin-positive cells expressed GFP
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in their nuclei. Furthermore, the GFP^+ cells from isolated glomeruli of [GFP→B6]mice exhibited structural alterations against AngII stimulation. These findings suggest that bone marrow-derived cells may have the potential to differentiate into glomemlar mesangial cells.
2.Mechanism that mediates the progression of diabetic nephropathy (DN) and role of renal progenitor cells in renal tissue repair.
We established obstructive nephropathy by unilateral ureteral obstruction (UUO) in obese diabetic mice (db/db) mice. At day 8,p27 expression on tubular epithelial cells (TEC) in UUO kidneys from +m/+m mice decreased to the same range as that in contralateral kidneys, while p27 expression on TEC in UUO kidneys from db/db mice was still up-regulated and prolonged. At day 8,the degree of macrophage infiltration and the intensity of α-smooth muscle expression in the interstitium of UUO kidney from db/db mice was markedly decreased compared to +m/+m mice. These data demonstrate that the expression of p27 in TEC is enhanced by UUO, and up-regulation of p27 may induce tubular hypertrophy and modulate tubulointerstitial inflammation in DN.
Next, we examined role of renal progenitor CD133^+ cells on tissue repair in the progression of renal damage. Of note, CD133^+ cells were observed in peritubular cell space of non-UUO kidney, whereas these cells were rare in the interstitium of UUO-kidney.
These findings suggest that renal progenitor CD133^+cells exist in the interstitium of adult kidney and may contribute to the repair of renal injury. Less
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