| 1.Research Institution | Kyoto University | |
| 2.Research Area | Integrated Fields | |
| 3.Research Field | Tissue Engineering | |
| 4.Term of Project | FY1996〜FY2000 | |
| 5.Project Number | 96I00204 | |
| 6.Title of Project | Tissue Engineering for Organ Regeneration |
| Name | Institution,Department | Title of Position |
| Yoshio Yamaoka | Kyoto University Graduate School of Medicine | Professor |
8.Core Members
| Names | Institution,Department | Title of Position |
| Kazutomo Inoue | Kyoto University Institute of Frontier Medical Science | Professor |
| Hiroo Iwata | Kyoto University Institute of Frontier Medical Science | Professor |
| Iwao Ikai | Kyoto University Graduate School of Medicine | Lecturer |
9.Cooperating Researchers
| Names | Institution,Department | Title of Position |
| Yoshihito Honda | Kyoto University Graduate School of Medicine | Professor |
| Kazuwa Nakao | Kyoto University Graduate School of Medicine | Professor |
| Masasi Komeda | Kyoto University Graduate School of Medicine | Professor |
10.Summary of Research Results
|
The "Tissue Engineering for Organ Regeneration" project has progressed through cooperative studies in medicine and engineering. In the artificial liver study, we've developed a liver support system using ex-vivo perfused porcine liver. We confirmed the beneficial effects of the system using the hDAF transgenic porcine liver in a liver assist device in vivo. In 1997, however, it was reported that multiple proviruses of porcine endogenous retrovirus (PERV) are integrated into the genome of all pigs, and virus particles, some of which are able to infect human cells, are released from normal pig cells. To evaluate the potential risk posed by the transmission of PERVs from porcine liver in the liver support system, baboons cross-circulated with this system were examined. A transient increase of PERV in blood samples of the baboons was detected, so we stopped clinical use of the device using porcine liver. In addition, we have developed the hybrid bioartificial liver using porcine hepatocytes, but it also poses a risk for PERV transmission. Therefore, we altered the source of hepatocytes for our bioartificial liver from porcine hepatocytes to human liver stem cells. We are now studying isolation techniques and characterization of these cells. For the bioartificial pancreas, we also have studied isolation of xenogeneic islet cells, development of membranes as immunological barriers, convenience, safety issues, and suitable portions for transplantation. However, since it is difficult to use xenogeneic islets in a bioartificial pancreas, clinically, we are studying alternative sources of islet cells. In addition, we have advanced basic scientific knowledge in the use of organ stem cells in the regeneration of retina, heart, vessels, fatty tissues of breast, kidneys and the urinary bladder. We are now making an effort to develop human cells as a resource for clinical use instead of xenogeneic biomaterial. |
11.Key Words
(1)Bioartificial Liver、(2)Bioartificial Pancreas、(3)Xenogeneic cells
(4)Human Stem Cell、(5)Immunoisolation、(6)Organ Regeneration
12.References
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| Cell Transplantation | in press | |||
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| Proc. Natl. Acad. Sci. USA | 95･ | 1998 | 2337-2342, | |
| Author | Title of Article | |||
| H. Itoh, | Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma | |||
| Journal | Volume | Year | Pages Concerned | |
| Clin-Exp-Pharmacol-Physiol | 26･(7) | 1999 | 558-560 | |
| Author | Title of Article | |||
| H. Itoh | Vascular stress response and endothelial vasoactive factors for vascular remodeling. | |||
| Journal | Volume | Year | Pages Concerned | |
| Diabetes Res. Clin. Pr. | 45･ | 1999 | 83-88 | |
| Author | Title of Article | |||
| M. Ishikawa | A Heart-specific increase in cardiotrophin-1 gene Expression precedes establishment of ventricular hypertension in genetically hypertensive rats. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Hypertens | 17･(6) | 1999 | 807-816 | |
| Author | Title of Article | |||
| K. Kuwahara | The effects of the selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic response in neonatal rat cardiac myocytes--possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy | |||
| Journal | Volume | Year | Pages Concerned | |
| FEBS-Lett | 452･(3) | 1999 | 314-318 | |
| Author | Title of Article | |||
| K. Kuwahara | Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro | |||
| Journal | Volume | Year | Pages Concerned | |
| Circulation | 100･ | 1999 | 1116-1124 | |
| Author | Title of Article | |||
| N. Sawada | Inhibition of Rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries | |||
| Journal | Volume | Year | Pages Concerned | |
| Circulation | 101･ | 2000 | 2030-2033 | |
| Author | Title of Article | |||
| Y. Fukunaga | Altered gene expression of uncoupling protein-2 and -3 in stroke-prone spontaneously hypertensive rats | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Hypertens | 18･ | 2000 | 1233-1238 | |
| Author | Title of Article | |||
| I. Hamanaka | Effects of Cardiotrophin-1 on Hemodynamics and Endocrine Function of the Heart. | |||
| Journal | Volume | Year | Pages Concerned | |
| Am. J. Physiol. | 279･(1) | 2000 | H388-396 | |
| Author | Title of Article | |||
| N. Tamura | Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc. | |||
| Journal | Volume | Year | Pages Concerned | |
| Natl. Acad. Sci. USA. | 97･(8) | 2000 | 4239-4244 | |
| Author | Title of Article | |||
| E. Ogawa | Outside-in Signaling of Fibronectin Stimulates Cardiomyocyte Hypertrophy in Cultured Neonatal Rat Ventricular Myocytes | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Mol. Cell. Cardiaol. | 32･(5) | 2000 | 765-776 | |
| Author | Title of Article | |||
| Y. Miyamoto | Replication protein Al reduces transcription of the endothelial nitric oxide synthase gene containing a T-786→C mutation associated with coronary spastic angina. | |||
| Journal | Volume | Year | Pages Concerned | |
| Human Molecular Genetics | 9･(18) | 2000 | 2629-2637 | |
| Author | Title of Article | |||
| S. Yura | Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Clin. Invest. | 105･ | 2000 | 749-755 | |
| Author | Title of Article | |||
| M. Aizawa-Abe | Pathophysiological role of leptin in obesity-related hypertension. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Clin. Invest. | 105･ | 2000 | 1243-1252 | |
| Author | Title of Article | |||
| H. Chusho | Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways. | |||
| Journal | Volume | Year | Pages Concerned | |
| Endocrinology | 141･ | 2000 | 3807-3813 | |
| Author | Title of Article | |||
| N. Sawada | cGMP-dependent protein kinase phosphorylated and inactivates RhoA. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 280･ | 2001 | 798-805 | |
| Author | Title of Article | |||
| K. Kuwahara | Neuron-Restrictive Silencer Element/Neuron-Restrictive Silencer Factor System Regulates Basal-and Endothelin-1-Inducible Atrial Natriuretic Peptide Gene Expression in Ventricular Myocytes | |||
| Journal | Volume | Year | Pages Concerned | |
| Mol Cell Biol. | 21･ | 2001 | 2085-2097 | |
| Author | Title of Article | |||
| M. Inoue | Oxidized low density lipoprotein regulates VEGF expression in human macrophages and endothelial cells through activation of PPAR g. | |||
| Journal | Volume | Year | Pages Concerned | |
| Arterioscler. Thromb. Vasc. Biol | in press | |||
| Author | Title of Article | |||
| K. Doi | C-type natriuretic peptide induces re-differentiation of vascular smooth muscle cells with accelerated re-endothelialization | |||
| Journal | Volume | Year | Pages Concerned | |
| Arterioscler. Thromb. Vasc. Biol | in press | |||
| Author | Title of Article | |||
| I. Hamanaka | Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS3/SSI-3 Is Involved in gp130 Resistance in Cardiovascular System in Rat Treated with Cardiotrophin-1 (CT-1) in vivo. | |||
| Journal | Volume | Year | Pages Concerned | |
| Circ. Res | in press | |||
| Author | Title of Article | |||
| H. Chusho | Dwarfism and early death in mice lacking C-type natriuretic peptide. | |||
| Journal | Volume | Year | Pages Concerned | |
| Proc. Natl. Acad. USA | in press | |||
| Author | Title of Article | |||
| Y. Tabata | De novo formation of adipose tissue by controlled release of basic fibroblast growth factor. | |||
| Journal | Volume | Year | Pages Concerned | |
| Tissue Engineering | 6･(3) | 2000 | 279-289 | |
| Author | Title of Book | ||
| Y. Ikada, editors Y. Yamaoka, Co-editor | Tissue Engineering for Therapeutic Use 1 | ||
| Publisher | Year | Pages | |
| Elsevier Science | 1998 | 159 | |
| Author | Title of Book | ||
| Y. Ikada, editors S. Enomoto, Co-editor | Tissue Engineering for Therapeutic Use 2 | ||
| Publisher | Year | Pages | |
| Elsevier Science | 1998 | 137 | |
| Author | Title of Book | ||
| Y. Ikada, editors T. Okano, Co-editor | Tissue Engineering for Therapeutic Use 3 | ||
| Publisher | Year | Pages | |
| Elsevier Science | 1999 | 161 | |
| Author | Title of Book | ||
| Y. Ikada, editors Y. Shimizu, Co-editor | Tissue Engineering for Therapeutic Use 4 | ||
| Publisher | Year | Pages | |
| Elsevier Science | 2000 | 192 | |
| Author | Title of Book | ||
| Y. Ikada, editors N. Ohshima, Co-editor | Tissue Engineering for Therapeutic Use 5 | ||
| Publisher | Year | Pages | |
| Elsevier Science | 2001 | 226 | |