Bone Marrow–Derived Mesenchymal Stem Cells Improve Islet Graft Function in Diabetic Rats

Figliuzzi, Marina; Cornolti, Roberta; Perico, Norberto; Rota, Cinzia; Morigi, Marina; Remuzzi, Giuseppe; Remuzzi, Andrea; Benigni, Ariela

doi:10.1016/j.transproceed.2008.11.015

Cited by 127 publications

(129 citation statements)

References 12 publications

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“…Besides osteogenic differentiation of seeded cells, an important precondition for bone formation is vascularisation of the implanted carriers. In this respect, it is interesting that bone marrow-derived mesenchymal stem cells have also shown increased production of vascular endothelial growth factor (VEGF) after transplantation facilitating vascularisation and survival of co-transplanted cells (Egana et al, 2009;Figliuzzi et al, 2009). This suggests that an ideal environment for seeding and culturing of MSCs in carriers for bone tissue engineering would promote not only osteogenic differentiation but also angiogenic activity of the transplanted MSCs for successful application of the seeded constructs in vivo.…”

Section: Introductionmentioning

confidence: 99%

Effect of fibrin on osteogenic differentiation and VEGF expression of bone marrow stromal cells in mineralised scaffolds: a three-dimensional analysis

Lohse

Schulz²,

Schliephake³

2012

eCM

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The aim of the present study was to test the hypothesis that a fibrin matrix enhances the osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) by human bone marrow stromal cells (hBMSCs) seeded into mineralised scaffolds. Porous calcium carbonate scaffolds were droplet seeded with hBMSCs using a matrix containing 3 % fibrinogen and cultured for 3 weeks. Seeded scaffolds without the fibrin matrix served as controls. The scaffolds were evaluated, using undecalcified thick sections, for fluorescence staining for nuclei, osteocalcin (OC) and VEGF. The sections were systematically scanned using optical sectioning and three dimensional distributions of cells and positive staining indicating expression of OC and VEGF were reconstructed from the z-stacks. The fibrin matrix maintained a significantly higher level of cell numbers after 2 d and 1 week and delayed the onset of osteogenic differentiation while sustaining a significantly higher level of OC and VEGF expression after 2 and 3 weeks, starting from the periphery of the scaffolds. There was a decrease in cell density from the periphery to the centre of the scaffolds in both groups The percentage of cells expressing OC and VEGF was significantly different between the centre and the periphery of the scaffolds in the fibrin(+) group but not in the controls. It is concluded that the fibrin matrix used appears to be a useful adjunct for supporting and sustaining osteogenic and angiogenic activity of hBMSCs in tissue engineered constructs. This could help to improve their performance in a clinical setting.

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Section: Introductionmentioning

confidence: 99%

Effect of fibrin on osteogenic differentiation and VEGF expression of bone marrow stromal cells in mineralised scaffolds: a three-dimensional analysis

Lohse

Schulz²,

Schliephake³

2012

eCM

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“…Filiuzzi et al demonstrated that the injection of 1 × 10 6 MSCs (obtained from the bone marrow) and 2 × 10 3 islets in the renal cortex of the Lewis rats, in which diabetes mellitus was induced by 65 mg/kg STZ, effectively reduced blood glucose level to under 200 mg/dl after 15 days, this levels remained stable until day 39 (Figliuzzi et al, 2009). Lin et al provided evidence of in vivo trans-differentiation of MSCs into IPCs in mice when 1 × 10 7 MSCs were injected into the tail vein of Wistar rats in which diabetes mellitus was induced by injection with 60 mg/kg STZ (Lin et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Preliminary evaluation of intravenous infusion and intrapancreatic injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of diabetic mice

et al. 2014

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Abstract-Type 1 diabetes mellitus is characterized by the destruction of pancreatic islet beta cells, which leads to insulin insufficiency, hyperglycemia, and reduced metabolic glucose level. Insulin replacement is the current standard therapy for type 1 diabetes mellitus but has several limitations. Pancreatic islet transplantation can result in the production of exogenous insulin, but its use is limited by immune-rejection and donor availability. Recent studies have shown that mesenchymal stem cells (MSCs) can transdifferentiate into insulin-producing cells (IPCs), which could be utilized for diabetes mellitus treatment. Previously published reports have demonstrated that MSC or IPC transplantation could produce significant improvement in mouse models of diabetes mellitus. This study was aimed at determining the effects of two different methods of MSC transplantation on the efficacy of diabetes mellitus treatment in mouse models. The MSCs were isolated from umbilical cord blood and were proliferated following a previously published procedure. Diabetes mellitus was induced in mice by streptozotocin (STZ) injection. Thirty days after transplantation, the weight of the mice treated by intra-venous infusion and intra-pancreatic injection was found to be 22% and 14% higher than that of the un-treated mice. The blood glucose concentrations in both intra-venous infusion and intra-pancreatic injection groups decreased and remained more stable than those in the control group. Moreover, insulin was detected in the serum of the treated mice, and the pancreas also showed gradual recovery. Based on the results of this preliminary investigation, intra-venous infusion seems more suitable than intra-pancreatic injection for MSC transplantation for diabetes mellitus treatment.

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“…Moreover, autologous [75], syngeneic [76][77][78] or allogeneic [78][79][80] MSCs have demonstrated immunomodu latory properties in animal models of islet transplantation. Complex mechanisms are involved including secretion of soluble factors (such as matrix metalloproteinase-2 and -9 [76] and IL 10 [81]), improvement of graft revascularization [77], and effects on immune cells (including the inhibition of maturation and function of DCs [82], downregulation of memory T cells [80], and induction of regulatory T cells [83]). Moreover, in non human primates, co-transplantation of allogeneic donor MSCs and islet cells led to significantly enhanced islet engraftment and function at 1 month posttransplant, and additional infusions of donor or third-party MSCs successfully treated rejection [84].…”

Section: Pancreas and Islet Transplantationmentioning

confidence: 99%

The use of mesenchymal stromal cells in solid organ transplantation

Delens

Jouret

Detry

et al. 2016

The Biology and Therapeutic Application of Mesenchymal Cells

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Bone Marrow–Derived Mesenchymal Stem Cells Improve Islet Graft Function in Diabetic Rats

Cited by 127 publications

References 12 publications

Effect of fibrin on osteogenic differentiation and VEGF expression of bone marrow stromal cells in mineralised scaffolds: a three-dimensional analysis

Effect of fibrin on osteogenic differentiation and VEGF expression of bone marrow stromal cells in mineralised scaffolds: a three-dimensional analysis

Preliminary evaluation of intravenous infusion and intrapancreatic injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of diabetic mice

The use of mesenchymal stromal cells in solid organ transplantation

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