Induction of immunotolerance using non-myeloablating stem cell transtplantation in swine model of small intestinal transplantation

• Project/Area Number: 17390352
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: TAGUCHI Tomoaki Kyushu University, Graduate School of Medical Sciences, Professor (20197247)
• Co-Investigator(Kenkyū-buntansha): SUITA Sachiyo Kyushu University, Hospital, Professor (30038856) ; NISHIMOTO Yuko Kyushu University, Hospital, Assistant Professor (00419574) ; MATSUZAKI Akinobu Kyushu University, Graduate School of Medical Sciences, Professor (90238999) ; SUMINOE Aiko Kyushu University, Hospital, Assistant Professor (80335968) ; TAJIRI Tatsuro Kyushu University, Graduate School of Medical Sciences, Associate Professor (80304806) ; 荻田 桂子 九州大学, 大学院・医学研究院, 助手 (40346771)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥16,620,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,020,000); Fiscal Year 2007: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2005: ¥9,000,000 (Direct Cost: ¥9,000,000)
• Keywords: small intestinal transplantation / non-myeloablating stem cell transplantation / chimerism / immunotolerance / MHC / large animal / miniature swine / living-related transplantation

Research Abstract

Survival rate after Small intestinal transplantation has been improved gradually in recent 10 years. However, incidence of acute as well as chronic rejection is still high, and late graft loss is sometimes happen. In order to overcome immunological obstacles, induction of tolerance is called for.
Non-myeloablating stem cell transplantation has been introduced as treatment tool for leukemia. In living-related organ transplantation, donor specific tolerance can be induced by this method. After tolerance induction by stem cell transplantation, small intestinal graft from the same donor can be accepted without immunosuppression. We have starting to establish this method using mini-swine model of small intestinal transplantation.
In the first year, operion technique of small intestinal transplantation, using miniature swine was established. Ileal graft was harvested with pedicle. Cutting site of each superior mesenteric vessel was radix of celiac trunks and portal vein. Then graft was anastosed to Aorta and graft vein was anastomosed to IVC by end-to-side fashion.
In the second year, non-myeloablating stem cell transplantation was started. Bone marrow cells were harvested from iliac bone. However the number of cells were not enough for tstem cell transplantation. Then we started irrigation of bone marrow, using two needle. After that the number of cells were increased. The numbers were identified by CD34 immunostaining.
In the third year, miniature swine, SLA established syngenic chrone, cannot be supplied by animal farm. Especially, combination of SLA 1 mismatch is impossible now. We have proposed the protochol of chemotherapy which can establish the non-myelloablating protochol.

Research Products

• [Journal Article] Morphological and physiological changes of interstitial cells of Cajal, after small bowel transplantation in rats (2007)
  • Author(s): Matsuura T, Masumoto K, leiri S, Nakatsuji T, Akiyoshi J, Nish imoto Y, Takahashi Y, Hayashid a M, Taguchi T, et. al.
  • Journal Title: Transpl Int 20(7) Pages: 616-624
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The influence of rejection on graft motility after intestinal transplantati on in swine:the possibility of using this method for the real-time moni toring of acute cellular rejection (2007)
  • Author(s): Matsuura T, Taguchi T, Hayashi da M, Ogita K, Takada N, Nish imoto Y, Taguchi S, Uesugi T, K ondo T, Hirose R, Suita S, et. al.
  • Journal Title: J Pediatr Surg 42(8) Pages: 1377-1385
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Successful prolonged Rituximab treatment for post-transplant lymphopro liferative disorder following living donor liver transplantation in a child (2007)
  • Author(s): Hayashida M, Ogita K, Matsuur a T, Takahashi Y, Nishimoto Y, Ohga S, Hara T, Soejima Y, Tak etomi A, Maehara Y, Kohashi K, Tsuneyoshi M, Taguchi T, et. al.
  • Journal Title: Pediatr Transplant 11(6) Pages: 671-675
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Morphological and physiological changes of interstitial cells of Cajal after small bowel transplantation in rats (2007)
  • Author(s): Matsuura, T., Masumoto, K., Ieiri S., Nakatsuji, T., Akiyoshi, J., Nishimoto, Y., Hayashida, M., Taguchi, T., et. al.
  • Journal Title: Transpl Int 20(7) Pages: 616-624
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The influence of rejection on graft motility after intestinal transplantation in swine : the possibility of using this method for the real-time monitoring of acute cellular rejection (2007)
  • Author(s): Matsuura, T., Taguchi, T., Hayashida, M., Ogita, K., Takada, N., Nishimoto, Y., Taguchi, S., Uesugi, T., Kondo, T., Hirose, R., Suita, S., et. al.
  • Journal Title: J Pediatr Surg 42(8) Pages: 1377-1385
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Successful prolonged Rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child (2007)
  • Author(s): Hayashida, M., Ogita, K., Matsuura, T., Takahashi, Y., Nishimoto, Y., Ohga, S., Hara, T., Soejima, Y., Taketomi, A., Maehara, Y., Kohashi, K., Tsuneyoshi, M., Taguchi, T., et. al.
  • Journal Title: Pediatr Transplant 11(6) Pages: 671-675
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] (2007)
  • Author(s): Shono T, Taguchi T, Suita S, Nakanami N, Nakano H, et. al.
  • Journal Title: J Pediatr Surg 42(4) Pages: 681-684
  • Peer Reviewed
• [Journal Article] The evidence of maternal microchimerism in biliary atresia using fluore scent in situ hybridization. (2007)
  • Author(s): Hayashida M, Nishimoto Y, Matsuura T, Takahashi Y, Kohashi K, Souzaki R, Taguchi T, et. al.
  • Journal Title: J Pediatri Surg 42(12) Pages: 2097-2101
  • Peer Reviewed
• [Journal Article] Successful prolonged Rituximab treatment for post-transplant lymphopro liferative disorder following living donor liver transplantation in a child. (2007)
  • Author(s): Hayshida M, Ogita K, Matsuura T, Takahashi Y, Nishimoto Y, Ohga S, Hata T, Soejima Y, Taketomi A, Maehara Y, Kohashi K, Tsuneyoshi M, Taguchi T, et. al.
  • Journal Title: Pediatr Transplant 11(6) Pages: 671-675
  • Peer Reviewed
• [Journal Article] Clinical features of selenium deficiency in infants receiving long-term nutritional support. (2007)
  • Author(s): Masumoto K, Nagata K, Higashi M, Nakatsuji T, Uesugi T, Takahashi Y, Nishimoto Y, Kitajima J, Hikino S, Hara T, N akashima K, Nakashima K, Oishi R, Taguchi, et. al.
  • Journal Title: Nutrition 23(11-12) Pages: 782-787
  • Peer Reviewed
• [Journal Article] Improvement in the QOL using both Bianchi's procedure and the elosure of a jejunostomy in a case with short bowel syndrome. (2007)
  • Author(s): Masumato K, Souzaki R, Nagata K, Uesugi T, Nishimoto Y, Taguchi T, et. al.
  • Journal Title: Pediatr Surg Int 23(3) Pages: 285-288
  • Peer Reviewed
• [Journal Article] Intracellular calcium mobilization of the aganglionic intestine in the endothelin B reseptor gene deficiet rat. (2007)
  • Author(s): Nakatsuji T,Ieiri S,Masumoto K,Akiyoshi J,Taguchi T,Suita S, et. al.
  • Journal Title: J Pediatr Surg 42(10) Pages: 1663-1370
  • Peer Reviewed
• [Journal Article] Increased expression of c-fos and c-jun in the rat small intestinal epithelium after ischemia-reperfusion injury : a possible correlation with the proliferation or apoptosis of intestinal epithelial cells (2006)
  • Author(s): Shima.Y, Tajiri.T, Taguchi.T, Suita.S
  • Journal Title: Journal of Pediatric Surgery 41 Pages: 830-836
• [Journal Article] Experimental Study Concerning Safety Dosage of OK-432 for Intrauterine Treatment (2006)
  • Author(s): Ogita.K, Taguchi.T, Suita.S
  • Journal Title: Asian Journal of Surgery 29(3) Pages: 202-206
• [Journal Article] Relationship Between Real-Time Monitoring of the Graft Motility and Mucosal Histology in Swine Intestinal Transplantation (2006)
  • Author(s): Matsuura.T, Taguchi.T, Hayashida.M, Ogita.K, Takada.N, Nishimoto.Y, Taguchi.S, Uesugi.T, Kondo.T, Hirose.R, Suita.S
  • Journal Title: Transplantation Proceedings 38 Pages: 1851-1852
• [Journal Article] Safe Techniques For Inserting The Hickman Catheter In Pediatric Patients (2006)
  • Author(s): Masumoto.K, Uesugi.T, Nagata.K, Takada.N, Taguchi.S, Ogita.K, Yamanouchi.T, Taguchi.T, Suita.S
  • Journal Title: Pediatric Hematology and Oncology 23 Pages: 531-540
• [Journal Article] New classification of hypoganglionosis : congenital and acquired hypoganglionosis (2006)
  • Author(s): Taguchi.T, Masumoto.K, Ieiri.S, Nakatsuji.T, Akiyoshi.J
  • Journal Title: Journal of Pediatric Surgery 41 Pages: 2046-2051
• [Journal Article] Auxiliary Partial Orthotopic Living Donor Liver Transplantation for a Child with Congenital Absence of the Portal Vein (2006)
  • Author(s): Soejima.Y, Taguchi.T, Ogita.K, Taketomi.A, Yoshizumi.T, Uchiyama.H, Ohno.T, Shimada.M, Maehara.Y
  • Journal Title: Liver Transplantation 12 Pages: 845-849
• [Journal Article] An abnormal distribution of c-kit positive cells in the normoganglionic segment can predict a poor clinical outcome in patients with Hirschsprung's disease (2005)
  • Author(s): Taguchi T, Suite S, Masumoto K, Nagasaki A
  • Journal Title: Eur J Pediatr Surg 15 Pages: 153-158
• [Journal Article] Efficacy of OK-432 local injection for the treatment of a neonatal branchial cleft cyst (2005)
  • Author(s): Taguchi S, Tatsuta K, Ieiri S, Taguchi T, Suita S
  • Journal Title: Pediatr Surg Int 21 Pages: 1004-1006
• [Journal Article] Hirschsprung's disease in Japan : analysis of 3852 patients based on a nationwide survey in 30 years (2005)
  • Author(s): Suita S, Taguchi T, Ieiri S, Nakatsuji T
  • Journal Title: J Pediatr Surg 40 Pages: 197-202
• [Journal Article] Endoscopic diverticulotomy for symptomatic pediatric esophageal diverticula (2005)
  • Author(s): Nishimoto Y, Taguchi T, Ogita K, Hashizume M, Suita S
  • Journal Title: Pediatr Surg Int 21 Pages: 50-53
• [Journal Article] Effect of a valine-rich diet on a rat model of short bowel syndrome (2005)
  • Author(s): Takada N, Ogita K, Taguchi T, Masumoto K, Suita S
  • Journal Title: Pediatr Surg Int 21 Pages: 899-906
  • NAID: 10028185034
• [Journal Article] Colonic stricture secondary to hemolytic uremic syndrome caused by Escherichia coli O-157 (2005)
  • Author(s): Masumoto K, Nishimoto Y, Taguchi T, Tsutsumi Y, Kanemitsu S, Hara T, Suita S
  • Journal Title: Pediatr Nephrol 20 Pages: 1496-1499
• [Journal Article] Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia (2005)
  • Author(s): Katsura S, Ogita K, Taguchi T, Suita S, Yoshizumi T, Soejima Y, Shimada M, Maehara Y
  • Journal Title: Pediatr Surg Int 21 Pages: 47-49
• [Presentation] New classification of hypoganglionosis-Congenital and acquired hypoga nglionosis (2006)
  • Author(s): Taguchi T, Masumoto K, leiri S, Nakatsuji T, Akiyoshi J
  • Organizer: 39th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Taipei
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] New classification of hypoganglionosis-Congenital and acquired Hypoganglionosis (2006)
  • Author(s): Taguchi, T., Masumoto, K., Ieiri, S., Nakatsuji, T., Akiyoshi, J
  • Organizer: 39th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Taipei
  • Description: 「研究成果報告書概要(欧文)」より