Using stem cells to produce insulin

Soria, Bernat; Gauthier, Benoit R.; Martı́n, Franz; Tejedo, Juan R.; Bedoya, Francisco J.; Rojas, Anabel; Hmadcha, Abdelkrim

doi:10.1517/14712598.2015.1066330

Cited by 23 publications

(18 citation statements)

References 186 publications

(149 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further evidence on PAX4 triggering β-cell commitment arises from transgenic mouse models where induction of PAX4 expression in early pancreatic epithelium, or in endocrine committed precursor cells induces the formation of insulin producing β-cells at the expense of all other islet cell phenotypes [25]. In agreement with this, ectopic expression of PAX4 potentiates the in vitro generation of insulin + β-like cells [26,27,28,29,30,31,32]. …”

Section: Pax4 In Islet Physiology: Key Player In β-Cell Generationmentioning

confidence: 98%

The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences

Lorenzo

Juárez-Vicente

Cobo-Vuilleumier

et al. 2017

Genes

View full text Add to dashboard Cite

Paired box 4 (PAX4) is a key factor in the generation of insulin producing β-cells during embryonic development. In adult islets, PAX4 expression is sequestered to a subset of β-cells that are prone to proliferation and more resistant to stress-induced apoptosis. The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations in PAX4 with the development of diabetes, independently of its etiology. Overexpression of this factor in adult islets stimulates β-cell proliferation and increases their resistance to apoptosis. Additionally, in an experimental model of autoimmune diabetes, a novel immunomodulatory function for this factor has been suggested. Altogether these data pinpoint at PAX4 as an important target for novel regenerative therapies for diabetes treatment, aiming at the preservation of the remaining β-cells in parallel to the stimulation of their proliferation to replenish the β-cell mass lost during the progression of the disease. However, the adequate development of such therapies requires the knowledge of the molecular mechanisms controlling the expression of PAX4 as well as the downstream effectors that could account for PAX4 action.

show abstract

Section: Pax4 In Islet Physiology: Key Player In β-Cell Generationmentioning

confidence: 98%

The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences

Lorenzo

Juárez-Vicente

Cobo-Vuilleumier

et al. 2017

Genes

View full text Add to dashboard Cite

show abstract

“…Although promising, cell functionality measured, as glucose-induced insulin secretion, tumorigenesis and remain major hurdles to overcome. Furthermore, PEC-Direct recipients still require an immunosuppressant regimen/therapy [24,25].…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Over the last five to ten years, there has been a number of advances on how to stimulate human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to differentiate into insulin-producing cells (for reviews see e.g. (12,13)). In fact, the field is now on the verge of bringing stem cell-derived insulin-producing cells into clinical trials.…”

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

View full text Add to dashboard Cite

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.

show abstract

Using stem cells to produce insulin

Cited by 23 publications

References 186 publications

The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences

The Diabetes-Linked Transcription Factor PAX4: From Gene to Functional Consequences

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

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

Contact Info

Product

Resources

About