Mesenchymal Stromal Cells to Halt the Progression of Type 1 Diabetes?

Carlsson, Per‐Ola; Korsgren, Olle; Blanc, Katarina Le

doi:10.1007/s11892-015-0616-3

Cited by 13 publications

(12 citation statements)

References 100 publications

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“…In contrast, other two non-responding patients exhibited slowly increased dosages of daily insulin and rapidly reduced levels of fasting and post-prandial C-peptide during the follow-up period. To the best of our knowledge, this was the first study of the effect of MSC infusion on patients with severe diabetes and our novel data extended previous findings111213 and support the notion that infusion with MSCs benefits T1D patients by preserving β-cell function. Notably, preservation of β-cell function and control of hyperglycemia are crucial for reducing and preventing long-term hyperglycemia-related complication, which is a leading cause of morbidity and mortality of diabetic patients1718.…”

Section: Discussionsupporting

confidence: 86%

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Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes

Hui

Jia

et al. 2016

Sci Rep

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Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves β-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1–2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes. In comparison with severe diabetes controls, MSC infusion reduced insulitis, decreased pancreatic TNF-α, and increased IL-10 and TGF-β1 expression in NOD mice. MSC infusion increased the percentages of splenic Tregs and levels of plasma IL-4, IL-10 and TGF-β1, but reduced the percentages of splenic CD8+ T and levels of plasma IFN-γ, TNF-α and IL-17A in NOD mice. Finally, infused MSCs predominantly accumulated in pancreatic tissues at 28 days post infusion. The effects of MSCs on preserving β-cell function and modulating inflammation tended to be dose-dependent and multiple doses of MSCs held longer effects in NOD mice. Hence, MSC transplantation preserved β-cell function in T1D patients and NOD mice with severe diabetes by enhancing Treg responses.

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Section: Discussionsupporting

confidence: 86%

“…Furthermore, infusion with MSCs preserves β-cell function in human patients with newly diagnosed T1D111213. However, there is no information on whether infusion with bone marrow MSCs can benefit T1D patients with ketoacidosis.…”

mentioning

confidence: 99%

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes

Hui

Jia

et al. 2016

Sci Rep

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“…Finally, a recent study demonstrated in vivo the ability of MSCs to inhibit the apoptotic pathway triggered by endoplasmic reticulum stress in transplanted pancreatic islets [ 47 ]. Taken together, these papers confirmed the promising use of MSCs for the treatment of diabetes, with the best results achieved when transplanted with pancreatic islets, and the first phase I/II clinical trials have demonstrated the safety and the feasibility of the application of MSCs ( ), and now larger studies are necessary to validate their effectiveness for diabetes treatment [ 48 ].…”

Section: Mscs and Diabetesmentioning

confidence: 74%

Mesenchymal Stem Cells as New Therapeutic Approach for Diabetes and Pancreatic Disorders

Scuteri

Monfrini

2018

IJMS

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Diabetes is a worldwide disease which actually includes different disorders related to glucose metabolism. According to different epidemiological studies, patients affected by diabetes present a higher risk to develop both acute and chronic pancreatitis, clinical situations which, in turn, increase the risk to develop pancreatic cancer. Current therapies are able to adjust insulin levels according to blood glucose peak, but they only partly reach the goal to abrogate the consequent inflammatory milieu responsible for diabetes-related diseases. In recent years, many studies have investigated the possible use of adult mesenchymal stem cells (MSCs) as alternative therapeutic treatment for diabetes, with promising results due to the manifold properties of these cells. In this review we will critically analyze the many different uses of MSCs for both diabetes treatment and for the reduction of diabetes-related disease development, focusing on their putative molecular mechanisms.

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“…Mesenchymal stem (stromal) cells has, due to their modulatory effects on immunity, inflammation and tissue repair, been suggested to be used to either halt beta-cell loss during T1D development or be used to protect and support pancreatic islets when transplanted. For the discussion of the use of mesenchymal stem cells in T1D, we refer to a recent review (11). This review will instead focus on the use of pluripotent stem cells (embryonic or induced) to generate new beta-like cells, give an overview of the current knowledge of such stem cell therapy outcomes in animal models of T1D and a proposed road map towards the clinical setting with special focus on the potential risks and hurdles which need to be considered.…”

Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Towards the clinical translation of stem cell therapy for type 1 diabetes

Espes¹,

Lau²,

Carlsson

2017

European Journal of Endocrinology

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Insulin-producing cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) have for long been a promising, but elusive treatment far from clinical translation into type 1 diabetes therapy. However, the field is now on the verge of moving such insulin-producing cells into clinical trials. Although stem cell therapies provide great opportunities, there are also potential risks such as teratoma formation associated with the treatment. Many considerations are needed on how to proceed with clinical translation, including whether to use hESCs or iPSCs, and whether encapsulation of tissue will be needed. This review aims to give an overview of the current knowledge of stem cell therapy outcomes in animal models of type 1 diabetes and a proposed road map towards the clinical setting with special focus on the potential risks and hurdles which needs to be considered. From a clinical point of view, transplantation of insulin-producing cells derived from stem cells must be performed without immune suppression in order to be an attractive treatment option. Although costly and highly labour intensive, patient-derived iPSCs would be the only solution, if not clinically successful encapsulation or tolerance induction protocols are introduced.

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Mesenchymal Stromal Cells to Halt the Progression of Type 1 Diabetes?

Cited by 13 publications

References 100 publications

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes

Mesenchymal Stem Cells as New Therapeutic Approach for Diabetes and Pancreatic Disorders

MECHANISMS IN ENDOCRINOLOGY: Towards the clinical translation of stem cell therapy for type 1 diabetes

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