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

Ikebukuro, Kazuya; Adachi, Yasushi; Suzuki, Yasuhiro; Iwasaki, Masanori; Nakano, K.; Kawakami, Yasushi; Matsubara, Hiromi; Yamada, Yoshio; Fujimoto, Shimpei; Seino, Yutaka; Oyaizu, Haruki; Shigematsu, Akio; Kiriyama, Naoko; Hamada, Y.; Kamiyama, Yasuo; Ikehara, Susumu

doi:10.1038/sj.bmt.1705500

Cited by 16 publications

(8 citation statements)

References 41 publications

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“…Ikebukuro et al (19) showed that islets and bone marrow cells, when injected into the liver using irradiation as immunosuppression, can increase the functionality of the cells for more than 365 days. In addition, Kawakami et al (22) discovered that basic fibroblast growth factor could increase vascularization and thus achieve islets viability for 112 days, when islets were injected in the subcutaneous tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Nonencapsulated islets may be injected into the liver (4,16,18,19,35,44,50,52) , kidney (5,14,15,16,17,24,27,28,32,34,35,42,46,47) , peritoneal cavity (11,35) , bone marrow (41) and subcutaneous tissue (22,48) . Ikebukuro et al (19) showed that islets and bone marrow cells, when injected into the liver using irradiation as immunosuppression, can increase the functionality of the cells for more than 365 days.…”

Section: Discussionmentioning

confidence: 99%

“…14 Subcutaneous tissue Sorenby et al (48) 200 to 1000 ± 6 Sorenby et al (49) 125 to 375 28 Liver Schneider S. et al (44) (19) …”

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confidence: 99%

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Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

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-Context -Diabetes mellitus type I affects around 240 million people in the world and only in the USA 7.8% of the population.It has been estimated that the costs of its complications account for 5% to 10% of the total healthcare spending around the world. According to World Health Organization, 300 million people are expected to develop diabetes mellitus by the year 2025. The pancreatic islet transplantation is expected to be less invasive than a pancreas transplant, which is currently the most commonly used approach. Objectives -To compare the encapsulated and free islet transplantation in rodents looking at sites of islet implantation, number of injected islets, viability and immunosuppression. Methods -A literature search was conducted using MEDLINE/PUBMED and SCIELO with terms about islet transplantation in the rodent from 2000 to 2010. We found 2,636 articles but only 56 articles from 2000 to 2010 were selected. Results -In these 56 articles used, 34% were encapsulated and 66% were nonencapsulated islets. Analyzing both types of islets transplantation, the majority of the encapsulated islets were implanted into the peritoneal cavity and the nonencapsulated islets into the liver, through the portal vein. In addition, the great advantage of the peritoneal cavity as the site of islet transplantation is its blood supply. Both vascular endothelial cells and vascular endothelial growth factor were used to stimulate angiogenesis of the islet grafts, increasing the vascularization rapidly after implantation. It also has been proven that there is influence of the capsules, since the larger the capsule more chances there are of central necrosis. In some articles, the use of immunosuppression demonstrated to increase the life expectancy of the graft. Conclusion -While significant progress has been made in the islets transplantation field, many obstacles remain to be overcome. Microencapsulation provides a means to transplant islets without immunosuppressive agents and may enable the performance of xenotransplantation. The use of alternative donor sources, fewer islets per capsule and the appropriate deployment location, such as the peritoneal cavity, may give a future perspective to the application of immunoprotective capsules and viability in clinical practice. A variety of strategies, such as genetic engineering, co-encapsulation, improvement in oxygen supply or the establishment of hypoxia resistance will also improve the islet transplantation performance. It remains to be determined which combination of strategies with encapsulation can fulfill the promise of establishing a simple and safe transplantation as a cure for diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

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“…IBM-BMT has various benefits compared with conventional BMT. For instance, IBM-BMT can facilitate donor hematopoiesis and reduce the severity of graft-versus-host disease [20,[26][27][28], based on which it has recently been attempted in humans [29]. The interaction of HSCs and stromal cells is crucial for the maintenance and proliferation of hematopoiesis [30,31].…”

Section: Discussionmentioning

confidence: 99%

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Shigematsu

Shi²,

Okigaki³

et al. 2010

Stem Cells and Development

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Fibroblast growth factor (FGF) and FGF receptor (FGFR) are expressed in various cells including endothelial progenitor cells and hematopoietic cells. The interaction between FGF and FGFR is associated with the proliferation, migration, and survival of these cells. In this report, we examined the effects of FGFR2 signaling on hematopoiesis in immature hematopoietic cells, using mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed by the Tie2 promoter (FGFR2 Tg mice). Under normal conditions, hematopoiesis of FGFR2 Tg mice and wild type (Wt) mice do not differ significantly, except for the weight and cell numbers of the thymus. However, the c-kit + Sca-1 + lineage À bone marrow cells (BMCs) of FGFR2 Tg mice facilitate the formation of colony-forming units of culture. When these BMCs were transplanted into the recipient bone marrow (intra-bone marrow-bone marrow transplantation), there was better reconstitution of donor hematopoietic cells. In the in vitro experiment, the c-kit + Sca-1 + lineage À BMCs from FGFR2 Tg mice showed fewer apoptotic cells than those from Wt mice. These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice.

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“…In addition, we have found that IBM-BMT is applicable to allografts of other organs and tissues in rats and mice, such as pancreas islets, legs, lungs, heart and ovary [78][79][80][81][82][83] .…”

Section: Intra Bone Marrow-bmt (Ibm-bmt) For Metabolic Disorders and mentioning

confidence: 99%

Immunomodulatory Properties and Therapeutic Application of Bone Marrow Derived-Mesenchymal Stem Cells

Ikehara²

2013

J Bone Marrow Res

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Mesenchymal stem cells (MSCs) are prototypical adult stem cells, identified as an adherent, fibroblast-like population positive for CD105, CD90 and CD73, and lacking hematopietic markers. MSCs can be isolated from different adult tissues including bone marrow (BM), umbilical cord, skeletal muscle and adipose tissue. MSCs have a potent immunomodulatory function via soluble factors, including PGE2, TGF-β, indoleamine 2,3-dioxygenase (IDO), IL-10, and HGF. Treatment with MSCs can improve type 1 diabetes, liver fibrosis and arthritis via their immunomodulatory function. Intra-bone marrowbone marrow transplantation (IBM-BMT) can replace not only hemopoietic stem cells (HSCs) but also MSCs. IBM-BMT seems to be the best strategy for allogeneic BMT, and may improve aging-related diseases, including type 2 diabetes and osteoporosis. IBM-BMT has also been shown to be the most effective strategy to prevent the rejection of organ allografts. This review summarizes the immunomodulatory properties and therapeutic application of bone marrow derived-MSCs.

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

Cited by 16 publications

References 41 publications

Islet transplantation in rodents: do encapsulated islets really work?

Islet transplantation in rodents: do encapsulated islets really work?

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Immunomodulatory Properties and Therapeutic Application of Bone Marrow Derived-Mesenchymal Stem Cells

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