A new approach for bone marrow-derived stem cells intrapancreatic autotransplantation in diabetic rats

Álvarez, Silvia; Jiménez, Luís Miguel; Murillo, Ana Zugasti; Gómez, Ignacio García; Ligero, José Manuel; Gomez-Pineda, Alfonso; Rollán-Landeras, Eduardo; Cuevas, Pedro L.; Jara-Albarrán, A.

doi:10.1002/micr.20283

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…Previous work suggested that mouse BMSCs spontaneously differentiate into endocrine pancreas cells in vivo [1]. In recent reports, BMSCs injected into the circulation of diabetic animals have been shown to partially/totally reverse the diabetic phenotypes and improve glucose control [2], [3], [4], [5], [6], [7], [8] [9] [10], [11] but with very poor direct β-cell differentiation, leading to other possible roles of BMSCs in pancreatic islet regeneration. Additionally, we previously reported that manipulation of culture conditions could induce β-cell differentiation in rat BMSCs expressing nestin [12].…”

Section: Introductionmentioning

confidence: 99%

β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

Milanesi

Lee

et al. 2012

PLoS ONE

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Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF) or pancreatic-duodenal homeobox 1 (PDX1) to reverse diabetes and whether these cells were differentiated into β-cells or mediated recovery through alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed hyperglycemia in more than half of the diabetic mice and induced overall improved survival and weight maintenance in all mice. Recovery was sustained only in the mice treated with hBMSCs-VEGF. However, de novo β-cell differentiation from human cells was observed in mice in both cases, treated with either hBMSCs-VEGF or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous β-cell regeneration and correlated with activation of the insulin/IGF receptor signaling pathway involved in maintaining β-cell mass and function. Our study demonstrated the possible benefit of hBMSCs for the treatment of insulin-dependent diabetes and gives new insight into the mechanism of β-cell recovery after injury mediated by hBMSC therapy.

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Section: Introductionmentioning

confidence: 99%

β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

Milanesi

Lee

et al. 2012

PLoS ONE

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“…The right femoral artery was punctured and a micro catheter was catheterized into the dorsal pancreatic artery. The ABMSCs according to their body weight (5×10 5 cells/kg) were directly injected into the dorsal pancreatic artery (11,34). …”

Section: Methodsmentioning

confidence: 99%

Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin-induced diabetes in miniature pigs: Real-time tracing with MRI in vivo

Tang

Xiao

Liu

et al. 2014

International Journal of Molecular Medicine

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Cellular replacement therapy for diabetes mellitus (DM) has received much attention. In this study, we investigated the effect of transplantation of autologous bone marrow-derived mesenchymal stem cells (ABMSCs) in streptozotocin (STZ)-induced diabetic miniature pigs. Miniature pig BMSCs were cultured, labeled with superparamagnetic iron oxide (SPIO) and transplanted into the pancreas of diabetic miniature pigs through targeted intervention. Blood glucose levels, intravenous and oral glucose tolerance test (OGTT), serum insulin, C-peptide and islets histology were analyzed. These transplanted cells were then identified by magnetic resonance imaging (MRI). The results showed that transplantation of ABMSCs reversed STZ-induced diabetes in miniature pigs. Blood glucose levels, intravenous, OGTT, serum insulin and C-peptide were significantly recovered in the diabetic minipigs with the autologous BMSC (DMAB) transplantation group. In addition, the number of islets was significantly increased in this group compared to the diabetic minipig control (DMC) group with conventional therapy. These data suggested the implantation of autologous BMSCs for type 1 diabetes treatment can partially restore the function of islet β cells and maintain blood glucose homeostasis. Transplanted autologous BMSCs may improve islet repairing by differentiating for new islets and change pancreatic microcirculation and be identified in a real-time manner using MRI in vivo.

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“…For the sake of uniformity, it was added on to all patients after six months as sitagliptin has been shown to improve survival of transplanted islet cells and causes neogenesis of pancreatic islets in animal models. [ 9 12 13 14 ] Self monitoring of blood glucose record was analyzed at each visit, HbA1c and lipid profile were estimated at three monthly intervals, while glucagon stimulated C-peptide, fasting plasma insulin and plasma glucose were assayed at the end of 12 months. Quality of life was assessed using World Health Organization Quality of Life WHOQOL-BREF (WHO, Dec 1996) and Treatment Related Impact Measure-Diabetes (TRIM-D) questionnaire, with permission from Novo Nordisk company at baseline and after 15 months of the follow-up.…”

Section: Aterials and M Ethodsmentioning

confidence: 99%

“…There is an evidence to suggest that stem cell transplantation can lead to improvement in pancreatic endocrine function and improvement in glycemic control through various mechanisms such as trans-differentiation or differentiation of ductal epithelial cells to islets cells and various growth factors along with stem cells may promote angiogenesis. [ 14 ] We describe the effect of autologous bone marrow derived stem cell transplantation (AMSCT) administered through targeted approach in patients with T2DM.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study

Bhansali

Upreti

Walia

et al. 2014

Indian J Endocr Metab

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Background:there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT) through targeted approach in Type 2 Diabetes Mellitus. This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM.Materials and Methods:Ten patients (8 men and 2 women) with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day), metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders), while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL) at the end of 15 months.Results:Six patients (60%) were ‘responders’ at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in ‘responders’ was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03), accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03), Homeostasis Model Assessment -β (P = 0.03) and QOL scores. However, ‘non-responders’ did not show any significant alterations in these parameters. No serious adverse events were noted.Conclusion:Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.

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A new approach for bone marrow-derived stem cells intrapancreatic autotransplantation in diabetic rats

Abstract: A technique is described for stem cell autotransplantation in rats. First we obtain autologous bone marrow-derived stem cells. Second, we inject the cells in the pancreas of the donor rat. This approach can be applied to experimental diabetes and other pancreatic processes.

Cited by 8 publications

References 26 publications

β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin-induced diabetes in miniature pigs: Real-time tracing with MRI in vivo

Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study

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