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ISOLATION OF STEM CELLS FOR THE KIDNEY AND EXPERIMENTAL TRIAL FOR THE REGENERATIVE MEDICINE

Research Project

Project/Area Number 13470211
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

IMAI Enyu  OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE, LECTURER, 医学系研究科, 講師 (00223305)

Co-Investigator(Kenkyū-buntansha) TAKENAKA Masaru  OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学系研究科, 助手 (20222101)
ISAKA Yoshitaka  OSAKA UNIVERSITY HOSPITAL, MEDICAL STAFF, 医学部附属病院, 医員(臨床研究)
ITO Takahito  OSAKA UNIVERSITY HOSPITAL, MEDICAL STAFF, 医学部附属病院, 医員(臨床研究)
MORIYAMA Toshiki  OSAKA UNIVERSITY HEALTH CENTER, LECTURER, 健康体育部, 講師 (30283815)
猪坂 善隆  大阪大学, 医学部・附属病院, 医員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥12,900,000 (Direct Cost: ¥12,900,000)
KeywordsREGENERATION / STEM CELL / GFP / RENAL FAILURE / TUBULAR EPITHELIAL CELL / SP CELL / RETINOIC ACID / NEPHROTIC SYNDROME / 骨髄幹細胞 / 糸球体上皮細胞 / GFPラット / PDGF
Research Abstract

Using transgenic rats which express GFP (Green Fluorescent Protein) throughout the body, we established chimeric rats which carry GFP(+) cells in all progeny of bone marrow. This system allowed us to find that bone marrow-derived cells contributed to the regeneration of mesangial cell in a self limiting acute glomerulonephritis model. We also showed that bone mar row cells were able to differentiate into mesangial cells in vitro. Both in vivo and in vitro, Platelet-derived growth factor-B was critical for the generation of bone marrow-derived mesangial cells. We also established a method to purify precursor cells/stem cells for mesangial cells from crude bone marrow preparation by using an unwoven mesh filter system. We purified side population (SP) cells from adult rat kidneys, and characterized them. In short, we proved that SP cells were not the stem cells for mesangial cells or tubular epithelial cells even though they clearly existed in the kidney. In order to find genes which are critical for the nephrogenesis, we compared a set of RNA obtained from neonatal rat kidneys to another set of RNA obtained from adult rat kidneys. By the suppression subtractive hybridization method, we found that retinaldehyde dehydrogenase type 2 (RALDH2) was highly enriched in the comma-shaped body and S-shaped body, and that RALDH2 was upregulated during the differentiation of glomerular epithelial cells. We also developed a new method which allows us to purify RNA from the nephrogenic zone of neonatal rat kidneys. Our extensive analysis revealed that the local concentration of retinoic acid that is produced by RALDH2 plays a critical role to repair injured podocytes, and that retinoic acid directly regulates the transcription of nephrin. Our further analysis about RALDH2 and other newly identified genes are under way.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (61 results)

All Other

All Publications (61 results)

  • [Publications] Azuma H, Takahara S, Matsumoto K, Ichimaru N, et al.: "Hepatocyte growth factor prevents the development of chronic allograft nephropathy in rats"J Am Soc Nephrol. 12. 1280-1292 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horio M, Ito A, Matsuoka Y, Moriyama T, et al.: "Apoptosis induced by hypertonicity in Madin Darley canine kidney cells : protective effect of betaine"Nephrol Dial Transplant. 16. 483-490 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito T, Suzuki A, Imai E, Okabe M, et al.: "Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling"J Am Soc Nephrol. 12. 2625-2635 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moriyama T, Kawada N, Nagatoya K, Takeji M, et al.: "Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction"Kidney Int. 59. 2095-2103 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Muso E, Mune M, Fujii Y, Imai E, et al.: "Significantly rapid relief from steroid resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy"Nephron. 89. 408-415 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagasawa Y, Takenaka M, Kaimori J, Matsuoka Y, et al.: "Rapid and diverse changes of gene expression in the kidneys of protein overload proteinuria mice detected by microarray analysis"Nephrol Dial Transplant. 16. 923-931 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura H, Isaka Y, Tsujie M, Akagi Y, et al.: "Electroporation mediated PDGF receptor IgG chimera gene transfer ameliorates experimental glomerulonephritis"Kidney Int. 59. 2134-2145 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oka K, Moriyama T, Imai E, Kyo M, et al.: "A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient"Clin Transplant. 15(Suppl5). 30-34 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsujie M, Isaka Y, Nakamura H, Kaneda Y, et al.: "Prolonged transgene expression in glomeruli using an EBV replicon vector system combined with HVJ liposomes"Kidney Int. 59. 1390-1396 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsujie M, Isaka Y, Nakamura H, Imai E, et al.: "Electroporation mediated gene transfer that targets glomeruli"J Am Soc Nephrol. 12. 949-954 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsujie M, Isaka Y, Nakamura H, Imai E, et al.: "Electroporation mediated gene transfer that targets glomeruli"J Am Soc Nephrol. 12. 949-954 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai E.: "Gene therapy approach in renal disease in the 21st century"Nephrol Dial Transplant. 16(Suppl5). 26-34 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Isaka Y, Imai E.: "Future strategy : gene therapy for diabetic nephropathy"Contrib Nephrol. 127-132 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito T, Suzuki A, Okabe M, Imai E, et al.: "Application of bone marrow derived stem cells in experimental nephrology"Exp Nephrol. 9. 444-450 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaimori JY, Takenaka M, Nagasawa Y, Nakajima H, et al.: "Quantitative analyses of osteopontin mRNA expression in human proximal tubules isolated from renal biopsy tissue sections of minimal change nephrotic syndrome and IgA glomerulonephropathy patients"Am J Kidney Dis. 39. 948-957 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawada N, Imai E, Karber A, Welch WJ, et al.: "A mouse model of angiotensin II slow pressor response : Role of oxidative stress"J Am Soc Nephrol. 13. 2860-2868 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatoya K, Moriyama T, Kawada N, Takeji M, et al.: "Y27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral ureteral obstruction"Kidney Int. 61. 1684-1695 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakajima H, Takenaka M, Kaimori JY, Nagasawa Y, et al.: "Gene expression profile of renal proximal tubules regulated by proteinuria"Kidney Int. 61. 1577-1587 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura H, Isaka Y, Tsujie M, Rupprecht HD, et al.: "Introduction of DNA enzyme for Egr1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats"Gene Ther. 9. 495-502 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara S, Moriyama T, Kokado Y, Hanafusa T, et al.: "Randamized prospective study of effects of benazepril in renal transplantation ; an analysis of safety and efficacy"Clin Exp Nephrol. 6. 242-247 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai E, Isaka Y.: "Targeting growth factors to the kidney : myth or reality?"Curr Opin Nephrol Hypertens. 11. 49-57 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai E, Ito T.: "Can bone marrow differentiate into renal cells?"Pediatr Nephrol. 17. 790-794 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki A, Ito T, Imai E, Yamato M, Iwatani H, Kawachi H, Hori M.: "Retinoids Regulate the Repairing Process of the Podocytes in Puromycin Aminonucleoside induced Nephrotic Rats"J.Am.Soc.Nephrol.. 14. 981-991 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, T.: "Stem cells on the kidney where are you from?"Nephrol Dial Transplant. 18. 1-4 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azuma H, Takahara S, Matsumoto K, Ichimaru N, et al.: "Hepatocyte growth factor prevents the development of chronic allograft nephropathy in rats"J Am Soc Nephrol. 12. 1280-1292 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horio M, Ito A, Matsuoka Y, Moriyama T, et al.: "Apoptosis induced by hypertonicity in Madin Darley canine kidney cells: protective effect of betaine"Nephrol Dial Transplant. 16. 483-490 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito T, Suzuki A, Imai E, Okabe M, et al.: "Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling"J Am Soc Nephrol. 12. 2625-2635 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moriyama T. Kawada N, Nagatoya K, Takeji M, et al.: "Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction"Kidney Int. 59. 2095-2103 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Muso E, Mune M, Fujii Y, Imai E, et al.: "Significantly rapid relief from steroid resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy"Nephron. 89. 408-415 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagasawa Y, Takenaka M, Kaimori J, Matsuoka Y, et al.: "Rapid and diverse changes of gene expression in the kidneys of protein overload proteinuria mice detected by microarray analysis"Nephrol Dial Transplant. 16. 923-931 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura H. Isaka Y, Tsujie M, Akagi Y, et al.: "Electroporation mediated PDGF receptor IgG chimera gene transfer ameliorates experimental glomerulonephritis"Kidney Int. 59. 2134-2145 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oka K, Moriyama T, Imai E, Kyo M, et al.: "A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient"Clin Transplant. 15 Suppl 5. 30-34 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsujie M, Isaka Y, Nakamura H, Kaneda Y, et al.: "Prolonged transgene expression in glomeruli using an EBV replicon vector system combined with HVJ liposomes."Kidney Int. 59. 1390-1396 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsujie M, Isaka Y, Nakamura H, Imai E, et al.: "Electroporation mediated gene transfer that targets glomeruli"J Am Soc Nephrol. 12. 949-954 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsujie M, Isaka Y, Nakamura H, Imai E, et al.: "Electroporation mediated gene transfer that targets glomeruli"J Am Soc Nephrol. 12. 949-954 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai E.: "Gene therapy approach in renal disease in the 21st century"Nephrol Dial Transplant. 16 Suppl 5. 26-34 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Isaka Y, Imai E.: "Future strategy: gene therapy for diabetic nephropathy"Contrib Nephrol. 127-132 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito T, Suzuki A, Ukabe M, Imai E, et al.: "Application of bone marrow derived stem cells in experimental nephrology"Exp Nephrol. 9. 444-450 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaimori JY, Takenaka M, Nagasawa Y, Nakajima H, et al.: "Quantitative analyses of osteopontin mRNA expression in human proximal tubules isolated from renal biopsy tissue sections of minimal change nephrotic syndrome and IgA glomerulonephropathy patients"Am J Kidney Dis. 39. 948-957 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawada N, Imai E, Karber A, Welch WJ, et al.: "A mouse model of angiotensin II slow pressor response: Role of oxidative stress"J Am Soc Nephrol. 13. 2860-2868 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatoya K, Moriyama T, Kawada N, Takeji M, et al.: "Y27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral ureteral obstruction"Kidney Int. 61. 1684-1695 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakajima H, Takenaka M, Kaimori JY, Nagasawa Y, et al .: "Gene expression profile of renal proximal tubules regulated by proteinuria"Kidney Int. 61. 1577-1587 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura H, Isake Y, Tsujie M, Rupprecht HD, et al.: "Introduction of DNA enzyme for Egr1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats"Gene Ther. 9. 495-502 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahara S, Moriyama T, Kokado Y, Hanafusa T, et al.: "Randamized prospective study of effects of benazepril in renal transplantation: an analysis of safety and efficacy"Clin Exp Nephrol. 6. 242-247 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai E, Isaka Y.: "Targeting growth factors to the kidney: myth or reality?"Curr Opin Nephrol Hypertens. 11. 49-57 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imai E, Ito T.: "Can bone marrow differentiate into renal cells?"Pediatr Nephrol. 17. 790-794 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki A, Ito T, Imai E, Yamato M, Iwatani H, Kawachi H, Hori M.: "Retinoids Regulate the Repairing Process of the Podocytes in Puromycin Aminonucleoside induced Nephrotic Rats"J. Am. Soc. Nephrol.. 14. 981-991 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito, T.: "Stem cells on the kidney where are you from?"Nephrol Dial Transplant. 18. 1-4 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki A, Ito T, Imai E, et al.: "Retinoids Regulate the Repairing Process of the Podocytes in Puromycin Aminonucleoside-induced Nephrotic Rats"J. Am. Soc. Nephrol.. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito, T: "Stem cells on the kidney-where are you from?"Nephrol Dial Transplant. 18. 1-4 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Imai E, Takahito Ito T: "Can bone marrow differentiate into renal cells?"Pediatr Nephrol. 17. 790-794 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito T, Suzuki A, Imai E, et al.: "Tornado extraction : a method to enrich and purify RNA from the nephrogenic zone of the neonatal rat kidney"Kidney Int. 62. 763-769 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaimori JY, Takenaka M, et al.: "Quantitative analyses of osteopontin mRNA expression in human proximal tubules isolated from renal biopsy tissue sections of minimal change nephrotic syndrome and IgA glomerulonephropathy patients"Am J Kidney Dis. 39. 948-957 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagatoya K, Moriyama T, et al.: "Y-27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral ureteral obstruction"Kidney Int. 61. 1684-1695 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakajima H, Takenaka M, et al.: "Gene expression profile of renal proximal tubules regulated by proteinuria"Kidney Int. 61. 1577-1587 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura H, Isaka Y, et al.: "Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha-smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats"Gene Ther. 9. 495-502 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito, T., Suzuki, A., Imai, E., Okabe, M., Hori, M.: "Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling"J. Am. Soc. Nephrol.. 12. 2625-2635 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, T., Suzuki, A., Okabe, M., Imai, E., Hori, M.: "Application of bone marrow-derived stem cells in experimental nephrology"Exp. Nephrol.. 9. 444-450 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatani, H., Ito, T., Imai, E., Suzuki, A., Ueda, N., Hori, M.: "In vitro conversion of bone marrow cells into mesangium-like cells"J. Am. Soc. Nephrol.. 12. 520A (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki, A., Ito, T., Imai, E., Iwatani, H., Fujii, T., Hori, M.: "Retinoic acid-generating enzyme, retinaldehyde dehydrogenise type 2 (RALDH2) regulates the differentiation of renal epithelial cells"J. Am. Soc. Nephrol.. 12. 527A (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, T., Suzuki, A., Imai, E., Iwatani, H., Isaka, Y., Nakamura, H., Hori, M.: "Effect of PDGF-B overexpressed in normal rat kidneys on the recruitment and differentiation of bone marrow-derived cells"J. Am. Soc. Nephrol.. 12. 679A (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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