scholarly journals Towards a Functional Cure for Diabetes Using Stem Cell-Derived Beta Cells: Are We There Yet?

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 191
Author(s):  
Stephanie Bourgeois ◽  
Toshiaki Sawatani ◽  
Annelore Van Mulders ◽  
Nico De Leu ◽  
Yves Heremans ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Beta Cell ◽  
Beta Cells ◽  
Pluripotent Stem Cells ◽  
Pancreatic Beta Cells ◽  
Embryonic Stem ◽  
Current Status ◽  
Attractive Alternative ◽  
Mature Beta Cells

Diabetes mellitus is a pandemic metabolic disorder that results from either the autoimmune destruction or the dysfunction of insulin-producing pancreatic beta cells. A promising cure is beta cell replacement through the transplantation of islets of Langerhans. However, donor shortage hinders the widespread implementation of this therapy. Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, represent an attractive alternative beta cell source for transplantation. Although major advances over the past two decades have led to the generation of stem cell-derived beta-like cells that share many features with genuine beta cells, producing fully mature beta cells remains challenging. Here, we review the current status of beta cell differentiation protocols and highlight specific challenges that are associated with producing mature beta cells. We address the challenges and opportunities that are offered by monogenic forms of diabetes. Finally, we discuss the remaining hurdles for clinical application of stem cell-derived beta cells and the status of ongoing clinical trials.

scholarly journals An overview on small molecule-induced differentiation of mesenchymal stem cells into beta cells for diabetic therapy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nimshitha Pavathuparambil Abdul Manaph ◽  
Kisha N. Sivanathan ◽  
Jodie Nitschke ◽  
Xin-Fu Zhou ◽  
Patrick T. Coates ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Beta Cell ◽  
Small Molecules ◽  
Beta Cells ◽  
Small Molecule ◽  
Pancreatic Beta Cells ◽  
Mature Beta Cells

Abstract The field of regenerative medicine provides enormous opportunities for generating beta cells from different stem cell sources for cellular therapy. Even though insulin-secreting cells can be generated from a variety of stem cell types like pluripotent stem cells and embryonic stem cells, the ideal functional cells should be generated from patients’ own cells and expanded to considerable levels by non-integrative culture techniques. In terms of the ease of isolation, plasticity, and clinical translation to generate autologous cells, mesenchymal stem cell stands superior. Furthermore, small molecules offer a great advantage in terms of generating functional beta cells from stem cells. Research suggests that most of the mesenchymal stem cell-based protocols to generate pancreatic beta cells have small molecules in their cocktail. However, most of the protocols generate cells that mimic the characteristics of human beta cells, thereby generating “beta cell-like cells” as opposed to mature beta cells. Diabetic therapy becomes feasible only when there are robust, functional, and safe cells for replacing the damaged or lost beta cells. In this review, we discuss the current protocols used to generate beta cells from mesenchymal cells, with emphasis on small molecule-mediated conversion into insulin-producing beta cell-like cells. Our data and the data presented from the references within this review would suggest that although mesenchymal stem cells are an attractive cell type for cell therapy they are not readily converted into functional mature beta cells.

scholarly journals miR-212/132-Enriched Extracellular Vesicles Promote Differentiation of Induced Pluripotent Stem Cells Into Pancreatic Beta Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunyu Bai ◽  
Qiwei Ren ◽  
Haifeng Liu ◽  
Xiangchen Li ◽  
Weijun Guan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Beta Cell ◽  
Induced Pluripotent Stem Cells ◽  
Beta Cells ◽  
Extracellular Vesicles ◽  
Pluripotent Stem Cells ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Induced Pluripotent

Pancreatic beta cell transplantation is the ideal method for treatment of type 1 diabetes mellitus (T1DM), and the generation of beta cells from induced pluripotent stem cells (iPSCs) of patients is a promising strategy. In this study, we improved a previous strategy to produce beta cells using extracellular vesicles (EVs) derived from mature beta cells and differentiated beta cells from iPSCs (i-Beta cells), which secreted insulin under glucose stimulation in vitro and ameliorated hyperglycemia in vivo. Mechanistic analyses revealed that EV-carried microRNA (miR)-212/132 (EV-miR-212/132) directly bound to the 3′ UTR of FBW7 to prevent its translation and FBW7 combined with NGN3 to accelerate its proteasomal degradation. EV-miR-212/132 stabilized NGN3 expression to promote differentiation of endocrine cells from induced iPSCs. Moreover, NGN3 bound to PDX1 to enhance transcription of endogenous miR-212/132 and formed a positive regulatory circuit that maintained the functions of mature pancreatic beta cells.ConclusionThis study describes a novel approach for beta cell production and supports the use of iPSCs for cell replacement therapy of T1DM.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

scholarly journals Strategy to Establish Embryo-Derived Pluripotent Stem Cells in Cattle

2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Human Diseases ◽  
Induced Pluripotent

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

scholarly journals Pluripotent stem cell SOX9 and INS reporters facilitate differentiation into insulin-producing cells

2021 ◽  
Author(s):  
Rabea Dettmer ◽  
Isabell Niwolik ◽  
Ilir Mehmeti ◽  
Anne Jörns ◽  
Ortwin Naujok
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Beta Cells ◽  
Pluripotent Stem Cells ◽  
Reporter Genes ◽  
Human Pluripotent Stem Cells ◽  
Endogenous Gene ◽  
Pancreatic Progenitors ◽  
Insulin Producing Cells ◽  
Endogenous Genes

AbstractDifferentiation of human pluripotent stem cells into insulin-producing stem cell-derived beta cells harbors great potential for research and therapy of diabetes. The SOX9 gene plays a crucial role during development of the pancreas and particularly in the development of insulin-producing cells as SOX9+ cells form the source for NEUROG3+ endocrine progenitor cells. For the purpose of easy monitoring of differentiation efficiencies into pancreatic progenitors and insulin-producing cells, we generated new reporter lines by knocking in a P2A-H-2Kk-F2A-GFP2 reporter genes into the SOX9 locus and a P2A-mCherry reporter gene into the INS locus mediated by CRISPR/CAS9-technology. The knock-ins enable co-expression of the endogenous genes and reporter genes, report the endogenous gene expression and enable the purification of pancreatic progenitors and insulin-producing cells using FACS or MACS. Using these cell lines we established a new differentiation protocol geared towards SOX9+ cells to efficiently drive human pluripotent stem cells into glucose-responsive beta cells.

Stem Cells in Neurodegenerative Disorders - A broad Overview

2021 ◽  
Author(s):  
Fariha Khaliq
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Pluripotent Stem Cells ◽  
Neurodegenerative Disorder ◽  
Human Fibroblasts ◽  
Embryonic Stem ◽  
Different Types ◽  
Induced Pluripotent

Stem cell therapy is an approach to use cells that have the ability of self-renewal and to differentiate into different types of functional cells that are obtained from embryo and other postnatal sources to treat multiple disorders. These cells can be differentiated into different types of stem cells based on their specific characteristics to be totipotent, unipotent, multipotent or pluripotent. As potential therapy, pluripotent stem cells are considered to be the most interesting as they can be differentiated into different type of cells with similar characteristics as embryonic stem cells. Induced pluripotent stem cells (iPSCs) are adult cells that are reprogrammed genetically into stem cells from human fibroblasts through expressing genes and transcription factors at different time intervals. In this review, we will discuss the applications of stem cell therapy using iPSCs technology in treating neurodegenerative disorder such that Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). We have also broadly highlighted the significance of pluripotent stem cells in stem cell therapy.

Stimulation of Embryonic Stem Cells to Differentiate into Pancreatic Beta-Cells by Co-axial Method with Momordica charantia L.

2010 ◽  
Vol 46 (0) ◽  
Author(s):  
Maria Gertrude C Derikito ◽  
Maria Wartenberg ◽  
Heinrich Sauer ◽  
Cynthia P Saloma ◽  
Ameurfina D Santos
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Embryonic Stem ◽  
Momordica Charantia ◽  
Stimulation Of
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