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1.
Int J Mol Sci ; 25(17)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39273600

ABSTRACT

Diabetes mellitus, a chronic and non-transmissible disease, triggers a wide range of micro- and macrovascular complications. The differentiation of pancreatic ß-like cells (PßLCs) from induced pluripotent stem cells (iPSCs) offers a promising avenue for regenerative medicine aimed at treating diabetes. Current differentiation protocols strive to emulate pancreatic embryonic development by utilizing cytokines and small molecules at specific doses to activate and inhibit distinct molecular signaling pathways, directing the differentiation of iPSCs into pancreatic ß cells. Despite significant progress and improved protocols, the full spectrum of molecular signaling pathways governing pancreatic development and the physiological characteristics of the differentiated cells are not yet fully understood. Here, we report a specific combination of cofactors and small molecules that successfully differentiate iPSCs into PßLCs. Our protocol has shown to be effective, with the resulting cells exhibiting key functional properties of pancreatic ß cells, including the expression of crucial molecular markers (pdx1, nkx6.1, ngn3) and the capability to secrete insulin in response to glucose. Furthermore, the addition of vitamin C and retinoic acid in the final stages of differentiation led to the overexpression of specific ß cell genes.


Subject(s)
Ascorbic Acid , Cell Differentiation , Diabetes Mellitus , Induced Pluripotent Stem Cells , Insulin-Secreting Cells , Tretinoin , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/cytology , Ascorbic Acid/pharmacology , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Tretinoin/pharmacology , Cell Differentiation/drug effects , Humans , Diabetes Mellitus/metabolism , Homeodomain Proteins/metabolism , Homeodomain Proteins/genetics , Signal Transduction/drug effects , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Trans-Activators/metabolism , Trans-Activators/genetics , Insulin/metabolism , Nerve Tissue Proteins
2.
Int J Mol Sci ; 21(22)2020 Nov 18.
Article in English | MEDLINE | ID: mdl-33217903

ABSTRACT

Diabetes mellitus (DM) is one of the main causes of morbidity and mortality, with an increasing incidence worldwide. The impact of DM on public health in developing countries has triggered alarm due to the exaggerated costs of the treatment and monitoring of patients with this disease. Considerable efforts have been made to try to prevent the onset and reduce the complications of DM. However, because insulin-producing pancreatic ß-cells progressively deteriorate, many people must receive insulin through subcutaneous injection. Additionally, current therapies do not have consistent results regarding the prevention of chronic complications. Leveraging the approval of real-time continuous glucose monitors and sophisticated algorithms that partially automate insulin infusion pumps has improved glycemic control, decreasing the burden of diabetes management. However, these advances are facing physiologic barriers. New findings in molecular and cellular biology have produced an extraordinary advancement in tissue development for the treatment of DM. Obtaining pancreatic ß-cells from somatic cells is a great resource that currently exists for patients with DM. Although this therapeutic option has great prospects for patients, some challenges remain for this therapeutic plan to be used clinically. The purpose of this review is to describe the new techniques in cell biology and regenerative medicine as possible treatments for DM. In particular, this review highlights the origin of induced pluripotent cells (iPSCs) and how they have begun to emerge as a regenerative treatment that may mitigate the pathology of this disease.


Subject(s)
Algorithms , Diabetes Mellitus/therapy , Induced Pluripotent Stem Cells/transplantation , Stem Cell Transplantation , Chronic Disease , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/pathology
3.
Metabolites ; 10(11)2020 Nov 19.
Article in English | MEDLINE | ID: mdl-33227979

ABSTRACT

Adipose tissue is the largest endocrine organ in humans and has an important influence on many physiological processes throughout life. An increasing number of studies have described the different phenotypic characteristics of fat cells in adults. Perhaps one of the most important properties of fat cells is their ability to adapt to different environmental and nutritional conditions. Hypothalamic neural circuits receive peripheral signals from temperature, physical activity or nutrients and stimulate the metabolism of white fat cells. During this process, changes in lipid inclusion occur, and the number of mitochondria increases, giving these cells functional properties similar to those of brown fat cells. Recently, beige fat cells have been studied for their potential role in the regulation of obesity and insulin resistance. In this context, it is important to understand the embryonic origin of beige adipocytes, the response of adipocyte to environmental changes or modifications within the body and their ability to transdifferentiate to elucidate the roles of these cells for their potential use in therapeutic strategies for obesity and metabolic diseases. In this review, we discuss the origins of the different fat cells and the possible therapeutic properties of beige fat cells.

4.
Rev. colomb. cardiol ; 27(3): 160-165, May-June 2020. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1289206

ABSTRACT

Resumen La pandemia por COVID-19 ha desencadenado un impacto tremendo en la humanidad debido a las implicaciones culturales, económicas y sociales que este tipo de infecciones ha ocasionado. Quizá preguntas iniciales, mirando en retrospectiva corta, acerca de los hechos que comenzaron esta infección, darían una luz para prevenir eventos de esta índole en el futuro. ¿Cuáles fueron las circunstancias que desencadenaron la pandemia?, ¿fue una serie de transmisiones zoonóticas que produjeron la infección en los humanos?, ¿ha tenido algo que ver el ambiente? El desafío de las grandes potencias para mantener la hegemonía, dará curso a una plétora de investigaciones acerca de la biología del virus, las variables epidemiológicas y las enfermedades crónicas de riesgo cardiovascular. En este manuscrito se analizan algunos de estos cuestionamientos.


Abstract The COVID-19 pandemic has had a tremendous impact on humanity due to the cultural, financial, and social implications caused by this type of infection. Perhaps some initial questions, looking at the short-term retrospective, about the facts that started this infection, could shed some light on preventing events of this kind in the future. What were the circumstances that triggered the pandemic? Was it a series of zoonotic transmissions that produced the infection in humans? Is it something to do with the environment? The challenge of the major powers to maintain dominance, will give rise to a plethora of studies on the biology of the virus, the epidemiological variables, and the chronic diseases of cardiovascular risk. Some of these questions are analysed in this article.


Subject(s)
Epidemiologic Factors , COVID-19 , Environment , Heart Disease Risk Factors
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