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Stem Cell Usage

Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets

Bone Marrow Transplantation volume 38, pages 657–664 (2006)Cite this article

Abstract

We have established a new method for allogeneic pancreatic islet (PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1Al, RT1Bl), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1An, RT1Bn) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of ‘9 Gy+IBM’(10/10 accepted), ‘9 Gy+PV’(7/10 accepted), ‘9 Gy+IV’(0/7 accepted), ‘9 Gy+PV+IBM’(8/8 accepted), ‘8.5 Gy+IBM’(4/9 accepted), ‘8.5 Gy+PV’(0/7 accepted), ‘8.5 Gy+IV’(0/7 accepted), ‘8.5 Gy+PV+IBM’(9/12 accepted), ‘8 Gy+IBM’(2/10 accepted) and ‘8 Gy+PV+IBM’(2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable strategy.

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Acknowledgements

We thank Ms Y Tokuyama, Ms M Murakami-Shinkawa, Ms S Miura, Ms K Hayashi and Ms A Kitajima for their expert technical assistance, and also Mr Hilary Eastwick-Field and Ms K Ando for the preparation of this manuscript. Grant support: ‘Gakunai Zyosei’ in Kansai Medical University, a grant from the ‘Haiteku Research Center’ of the Ministry of Education, a grant from ‘Millennium’ of the Ministry of Education, Culture, Sports, Science and Technology, grant-in-aid for scientific research (B) 11470062, grants-in-aid for scientific research on priority areas (A) 10181225 and (A) 1162221, and Health and Labor Science research grants (Research on Human Genome, Tissue Engineering Food Biotechnology), a grant from the ‘Science Frontier’ program of the Ministry of Education, Culture, Sports, Science and Technology, a grant from the ‘The 21st Century COE Program’ of the Ministry of Education, Culture, Sports, Science and Technology, and also a grant from the Department of Transplantation for Regeneration Therapy (sponsored by Otsuka Pharmaceutical Company Ltd.), a grant from Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd., as well as a grant from Japan Immunoresearch Laboratories Co., Ltd (JIMRO).

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Authors and Affiliations

  1. First Department of Pathology, Kansai Medical University, Osaka, Japan

    K Ikebukuro, Y Adachi, Y Suzuki, M Iwasaki, K Nakano, Y Koike, H Mukaide, H Oyaizu, A Shigematsu, N Kiriyama & S Ikehara

  2. Department of Surgery, Kansai Medical University, Osaka, Japan

    K Ikebukuro, Y Koike, H Mukaide, Y Hamada & Y Kamiyama

  3. Department of Anatomical Pathology, Kansai Medical University, Osaka, Japan

    Y Adachi

  4. Regeneration Research Center for Intractable Disease, Kansai Medical University, Osaka, Japan

    Y Adachi, Y Kamiyama & S Ikehara

  5. Transplantation Center, Kansai Medical University, Osaka, Japan

    Y Adachi, Y Kamiyama & S Ikehara

  6. Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Y Yamada, S Fujimoto & Y Seino

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Correspondence to S Ikehara.

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Ikebukuro, K., Adachi, Y., Suzuki, Y. et al. Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets. Bone Marrow Transplant 38, 657–664 (2006). https://doi.org/10.1038/sj.bmt.1705500

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