Advances in β-cell replacement therapy for the treatment of type 1 diabetes

Vantyghem, M. C.; Koning, Eelco J.P. de; Pattou, François; Rickels, Michael R.

doi:10.1016/s0140-6736(19)31334-0

Cited by 148 publications

(106 citation statements)

References 93 publications

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“…Replenishment of the beta-cell mass eradicated by the autoimmune attack has been the focus of intense research for the past 25 years exploring various cell types as a source of beta-cell replacement. One such approach has been pancreatic islet transplantation, which has emerged as a promising cellular therapy for T1DM [21]. Indeed, 877 individuals have received allogeneic isolated islets between 1999 and 2015 [22].…”

Section: Immune Blocking and Beta-cell Replacement Therapiesmentioning

confidence: 99%

“…Indeed, 877 individuals have received allogeneic isolated islets between 1999 and 2015 [22]. Unfortunately, the limited number of donors and low viability of islets after isolation combined with the progressive declined overtime in islet function as well as the detrimental effect of immunosuppressive agents posttransplantation has impinged the wide application of this approach [21]. Current efforts are focused on the encapsulation of islets to minimize the immune attack and increase islet viability and function [23].…”

Section: Immune Blocking and Beta-cell Replacement Therapiesmentioning

confidence: 99%

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Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Cobo-Vuilleumier

Gauthier

2020

Metabolism

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Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets the destruction of islet beta-cells resulting in insulin deficiency, hyperglycemia and death if untreated. Despite advances in medical devices and longer-acting insulin, there is still no robust therapy to substitute and protect beta-cells that are lost in T1DM. Attempts to refrain from the autoimmune attack have failed to achieve glycemic control in patients highlighting the necessity for a paradigm shift in T1DM treatment. Paradoxically, beta-cells are present in T1DM patients indicating a disturbed equilibrium between the immune attack and beta-cell regeneration reminiscent of unresolved wound healing that under normal circumstances progression towards an anti-inflammatory milieu promotes regeneration. Thus, the ultimate T1DM therapy should concomitantly restore immune self-tolerance and replenish the beta-cell mass similar to wound healing. Recently the agonistic activation of the nuclear receptor LRH-1/ NR5A2 was shown to induce immune self-tolerance, increase beta-cell survival and promote regeneration through a mechanism of alpha-to-beta cell phenotypic switch. This trans-regeneration process appears to be facilitated by a pancreatic anti-inflammatory environment induced by LRH-1/NR5A2 activation. Herein, we review the literature on the role of LRH1/NR5A2 in immunity and islet physiology and propose that a cross-talk between these cellular compartments is mandatory to achieve therapeutic benefits.

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Section: Immune Blocking and Beta-cell Replacement Therapiesmentioning

confidence: 99%

Section: Immune Blocking and Beta-cell Replacement Therapiesmentioning

confidence: 99%

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Cobo-Vuilleumier

Gauthier

2020

Metabolism

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“…Anatomical separation between mother and fetus by the placenta. Anatomic separation of allograft is under study in the field of islet transplantation using incapsulated islets to physically block host immunity from interacting with transplanted islets [127]. Hypothetically, islets could also be placed in areas of "immune privilege", such as in the cerebral spinal fluid, testis, or uterus.…”

Section: Lessons Learned From Fetomaternal Tolerance For Transplantationmentioning

confidence: 99%

Medawar's Paradox and Immune Mechanisms of Fetomaternal Tolerance

Rendell¹,

Bath²,

Brennan³

2020

OBM Transplantation

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Brazilian-born British biologist Dr. Peter Medawar played an integral role in developing the concepts of immunologic rejection and tolerance, which led to him receiving the Nobel Prize "for the discovery of acquired immunologic tolerance" and eventually made organ transplantation a reality. However, at the time of his early work in tolerance, a paradox to his theories was brought to his attention; how was pregnancy possible? Pregnancy resembles organ transplantation in that the fetus, possessing paternal antigens, is a semiallogeneic graft that can survive without immunosuppression for 9 months. To answer this question, Medawar proposed three hypotheses of how a mother supports her fetus in utero, now known as "Medawar's Paradox." The mechanisms that govern fetomaternal tolerance are still incompletely understood but may provide critical insight into how to achieve immune tolerance in organ transplantation. Here, we review current understanding of the

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“…T1D is an autoimmune disease caused by inflammatory β‐cell destruction, leading to the insufficient secretion of insulin . Patients with T1D are varied and quite heterogeneous in β‐cell function and its speed of progression .…”

Section: Introductionmentioning

confidence: 99%

Complicated curve association of body weight at diagnosis with C‐peptide in children and adults with new‐onset type 1 diabetes

Gong

Zhong

et al. 2020

Diabetes Metabolism Res

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Aim: To investigate the association of body mass index (BMI) or BMI z-score (BMIz) at diagnosis with β-cell function in new-onset type 1 diabetes (T1D) patients in children and adults.Methods: This was a retrospective cohort study; 256 children (<18 years) and 245 adults (≥18 years) with less than 1-year duration were recruited and followed for 4 years with an interval of 12 months. Smooth curve fitting, a two-piecewise linear model, and Cox proportional hazards models were utilized to investigate the influence of BMI/BMIz on C-peptide levels.Results: Heavier patients (BMIz ≥ −1 in children and BMI in adults ≥20.2 kg/m 2 ) had greater C-peptide with a complicated J curve in all age groups after adjustment for age of onset, sex, and disease duration. Moreover, after 4 years of follow-up, patients with higher BMI/BMIz had a lower risk of β-cell failure (HR = 0.7; 95% CI, 0.6-1.0; P = .026). However, no association was found between baseline BMI/BMIz at diagnosis and C-peptide rate of decline during 1 year follow-up.Conclusion: Association between BMI/BMIz and C-peptide in T1D followed a complicated J curve pattern, and heavier patients had greater C-peptide at diagnosis and a lower risk of β-cell failure at 4 years, suggesting that baseline BMI is a useful predictor for β-cell function in patients with T1D.

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Advances in β-cell replacement therapy for the treatment of type 1 diabetes

Cited by 148 publications

References 93 publications

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Time for a paradigm shift in treating type 1 diabetes mellitus: coupling inflammation to islet regeneration

Medawar's Paradox and Immune Mechanisms of Fetomaternal Tolerance

Complicated curve association of body weight at diagnosis with C‐peptide in children and adults with new‐onset type 1 diabetes

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