Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function

Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Formicola, Roberta; Doglioni, Claudio; Tiboni, Francesca; Ferrari, G.; Nano, Rita; Chwalek, Karolina; Lammert, Eckhard; Bonifacio, Ezio; Borg, Danielle J.; Piemonti, Lorenzo

doi:10.1002/stem.314

Cited by 50 publications

(38 citation statements)

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“…Several reports have indicated that MSCs have beneficial effects in different transplantation models, including islet grafts [12][13][14][15][16][17][18][19], and several different mechanisms have been thought to account for these effects, some of which are unlikely to account for our observations. Our results do not support the suggestion that transplantation of MSCs alone is sufficient to reverse hyperglycaemia in streptozotocin-treated rodents, either by enhancing regeneration of pancreatic beta cells [26] or through other paracrine effects [11].…”

Section: Discussionmentioning

confidence: 65%

“…These properties make MSCs excellent candidates for improving the survival of transplanted islets. Several recent studies in experimental animals have reported that co-transplantation of islets and MSCs produces superior outcomes to islet-alone grafts [12][13][14][15][16][17][18][19]. To date, these beneficial effects have been largely attributed to direct or indirect actions of MSCs in promoting islet survival and function by enhancing graft revascularisation [13,17,19] or by suppressing immune or inflammatory responses [12,[14][15][16]18].…”

Section: Introductionmentioning

confidence: 99%

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Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

et al. 2011

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Aims/hypothesis Recent studies have shown that mesenchymal stem cells (MSCs) secrete several factors that improve survival and function of transplanted islets. Implantation of islets beneath the kidney capsule results in morphological changes, due to interactions of the graft with the host, thus impairing islet function. We co-transplanted MSCs with islets to determine their effects on the remodelling process and studied graft function in a mouse model of minimal islet mass. Methods Islets were syngeneically transplanted, either alone or with kidney-derived MSCs, underneath the kidney capsule of streptozotocin-induced diabetic C57Bl/6 mice. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests carried out. Hormone contents of grafts and pancreas were assessed by radioimmunoassay. Graft morphology and vascularisation were evaluated by immunohistochemistry. Results MSCs improved the capacity of islet grafts to reverse hyperglycaemia, with 92% of mice co-transplanted with MSCs reverting to normoglycaemia, compared with 42% of those transplanted with islets alone. Average blood glucose concentrations were lower throughout the 1 month monitoring period in MSC co-transplanted mice. MSCs did not alter graft hormone content. Islets co-transplanted with MSCs maintained a morphology that more closely resembled that of islets in the endogenous pancreas, both in terms of size, and of endocrine and endothelial cell distribution. Vascular engraftment was superior in MSC co-transplanted mice, as shown by increased endothelial cell numbers within the endocrine tissue. Conclusions/interpretation Co-transplantation of islets with MSCs had a profound impact on the remodelling process, maintaining islet organisation and improving islet revascularisation. MSCs also improved the capacity of islets to reverse hyperglycaemia.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

et al. 2011

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“…However, this study lacks lineage tracing data and derives some of the conclusions from observations made in mice. The implied involvement of mesenchymal cells (CD45 + cells from marrow), as suggested by Sordi et al 18 cannot be co-related to human studies. In fact, a study involving analysis of 4,192 islets from 31 human patients (2 diabetic) who received a marrow transplant from donor of opposite sex, did not show any conversion of bone-marrow mesenchymal cells to insulin-producing cells.…”

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confidence: 91%

“…This thought was also supported by a similar study demonstrating presence of CD105 + / CD73 + /CD90 + mesenchymal stem cells in the freshly isolated islets. 9 Another article published this year by Sordi et al 18 suggests that mesenchymal cells in the cultures of human islets originate from non-beta cells and bone marrow may be the origin of these cells. However, this study lacks lineage tracing data and derives some of the conclusions from observations made in mice.…”

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confidence: 99%

Epithelial-to-mesenchymal transition in pancreatic islet β cells

Joglekar¹,

Hardikar²

2010

Cell Cycle

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“…Izumida et al reported that proliferative activity and differentiative response in the pancreatic ductal cells were significantly raised once rats were treated with HGF positive BMSCs [49]. Sordi et al found that BMSCs of bone marrow origin facilitated the restoration of normoglycemia and the neovascularization of the islet graft [50]. which was confirmed by a recently study by Rackham et al that islets co-transplanted with BMSCs maintained a morphology that more closely resembled that of islets in the endogenous pancreas both in terms of size, endocrine and endothelial cell distribution [51].…”

Section: Bmscs Support Islet Functionmentioning

confidence: 99%

Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

Wu¹

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revised all my manuscripts and gave me the courage and the skills to write and present as a non-native English speaker.I must acknowledge as well the many friends, colleagues, students, teachers, and other librarians who assisted, advised, and supported my research and writing efforts over the years. Especially, I need to express my gratitude and deep appreciation to my wife Chengcheng Liu whose understanding, wisdom, and sense of humor have supported, enlightened, and entertained me over many years. She has consistently helped me keep perspective on what is important in life and shown me how to deal with reality.

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Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function

Cited by 50 publications

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Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

Epithelial-to-mesenchymal transition in pancreatic islet β cells

Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

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