Bone marrow as an alternative site for islet transplantation

Cantarelli, Elisa; Melzi, Raffaella; Mercalli, Alessia; Sordi, Valeria; Ferrari, G.; Lederer, Carsten W.; Mrak, Emanuela; Rubinacci, Alessandro; Ponzoni, Maurilio; Sitia, Giovanni; Guidotti, Luca G.; Bonifacio, Ezio; Piemonti, Lorenzo

doi:10.1182/blood-2009-03-209973

Cited by 72 publications

(59 citation statements)

References 53 publications

(99 reference statements)

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“…Several recent studies have suggested that adult bone marrow cells can influence beta-cell regeneration in diabetic animals [26][27][28][29][30][31][32]. Other reports, however, have contradicted these findings [33,34].…”

Section: Discussionmentioning

confidence: 49%

“…Pluripotent mesenchymal stem cells in adult bone marrow have the capacity to differentiate into a number of neuroectodermal [38], endothelial [39], epithelial [40], and muscle [41] cells. Bone marrow is capable of maintaining pancreatic islets in the absence of immunosuppression, and can constitute an immunoprivileged environment for engraftment [31,42]. Transplantation of bone marrow derived cells into diabetic mice can reducehyperglycemia through proliferation of β-cells, differentiation of pancreatic stem cells to contribute to the rege- neration of β-cells [28,29,43,44], and improve islet graft function by promoting graft vascularization [31,45].…”

Section: Discussionmentioning

confidence: 99%

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Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Wang¹,

Xiong²,

Hassani³

et al. 2011

JDM

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We have previously demonstrated that allogeneic human bone marrow (BM) supports human islet function and longevity in vitro. We hypothesize that BM supporting human islets may include to increase β-cell in cultured islets. In this study, we developed a method to quantify insulin-producing β cells from cultured islets by using immunofluorescent staining and flow cytometry analysis to explore this possibility. The results show that human islets cocultured with BM for 39 days contained a significantly higher number of insulin-positive β cells (42.3% ± 4.5%) compared to the islet-only cultures (1.15% ± 0.78%), and increased insulin release levels evaluated by ELISA is consistent with increased β cells in same culture condition. Human islet culture with BM significantly increase β-cells while islet only culture lost β-cells in same culture period supports the possibility of BM increasing β-cells in cultured islets.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Wang¹,

Xiong²,

Hassani³

et al. 2011

JDM

View full text Add to dashboard Cite

show abstract

“…It consists of islet graft implantation directly into the recipient's bone marrow [52]. This approach has proven effective in a murine model of syngeneic islet transplantation.…”

Section: Potential Of Bone Marrow-derived Stem Cells To Improve Isletmentioning

confidence: 99%

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Fotino

Ricordi²,

Lauriola

et al. 2010

Rev Diabet Stud

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■ AbstractThe bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMSC) transplantation (BMT) may assist in achieving tissue repair and regeneration, and in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMSC to preserve functional beta-cell mass in subjects with type 1 and type 2 diabetes, and to favor engraftment and survival of transplanted islets. Additional trials are evaluating the impact of BMT (i.e., mesenchymal stem cells) on the progression of diabetes complications. This article reviews the progress in the field of BMSC for the treatment of subjects with insulindependent diabetes, by combining allogeneic islet transplantation with donor-specific BMSC. Clinical data is summarized from pilot studies performed at our research center over the last two decades.

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“…In fact, islets engrafted efficiently in the BM of diabetic mice. These animals showed a near-normal glucose metabolism for more than a year [79].…”

Section: Sites For Co-localization Of Islets and Stem Cellsmentioning

confidence: 99%

Mesenchymal Stem Cells as Feeder Cells for Pancreatic Islet Transplants

Sordi¹,

Piemonti²

2010

Rev Diabet Stud

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■ AbstractAllogeneic islet transplant serves as a source for insulinsecreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients.

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Bone marrow as an alternative site for islet transplantation

Cited by 72 publications

References 53 publications

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Mesenchymal Stem Cells as Feeder Cells for Pancreatic Islet Transplants

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