scholarly journals Development of islet organoids from human induced pluripotent stem cells in a cross-linked collagen scaffold

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shruti Sandilya ◽  
Shashi Singh

AbstractIslets organoids would have value in the cell replacement therapy for diabetes apart from usual personalized drug screening routes. Generation of a large number of Islets like clusters, with ability to respond to glucose stimulation appears to be an ideal choice. In this study we have generated islet organoids with the ability to respond to glucose stimulation by insulin release. The source of the cells was an iPSC cell line differentiated into the pancreatic progenitors. These cells were assembled in matrigel or cross-linked collagen scaffold and compared for their efficacy to release insulin upon stimulation with glucose. The assembled organoids were examined by immunohistochemistry and expression of the relevant marker genes. The organoids showed expression of islet like markers in both - matrigel and crosslinked collagen scaffold. The islet organoids in both the cases showed release of insulin upon stimulation with glucose. The crosslinked collagen scaffold is quite stable and supports islet cells growth and function.

2020 ◽  
Vol 9 (1) ◽  
pp. 121-136
Author(s):  
Akram Al Abbar ◽  
Siew Ching Ngai ◽  
Nadine Nograles ◽  
Suleiman Yusuf Alhaji ◽  
Syahril Abdullah

2010 ◽  
Vol 7 (suppl_6) ◽  
Author(s):  
Nigel G. Kooreman ◽  
Joseph C. Wu

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability (i) to duplicate indefinitely while maintaining pluripotency and (ii) to differentiate into cell types of all three embryonic germ layers. These two properties of ESCs and iPSCs make them potentially suitable for tissue engineering and cell replacement therapy for many different diseases, including Parkinson's disease, diabetes and heart disease. However, one critical obstacle in the clinical application of ESCs or iPSCs is the risk of teratoma formation. The emerging field of molecular imaging is allowing researchers to track transplanted ESCs or iPSCs in vivo , enabling early detection of teratomas.


2020 ◽  
Vol 129 (5) ◽  
pp. 1051-1061
Author(s):  
D. Merrill Dane ◽  
Khoa Cao ◽  
Yu-An Zhang ◽  
Kemp H. Kernstine ◽  
Amiq Gazdhar ◽  
...  

To examine whether the secreted products of human induced pluripotent stem cells (iPSCs) facilitate innate adaptive responses following loss of lung tissue, adult dogs underwent surgical removal of one lung, then received repeated administration of iPSC secretory products via inhalational delivery compared with control treatment. Inhalation of iPSC secretory products enhanced capillary formation and beneficial structural remodeling in the remaining lung, leading to improved lung function.


2020 ◽  
Vol 55 (8) ◽  
pp. 763-774
Author(s):  
Yasufumi Koterazawa ◽  
Michiyo Koyanagi-Aoi ◽  
Keiichiro Uehara ◽  
Yoshihiro Kakeji ◽  
Takashi Aoi

Abstract Background The esophagus is known to be derived from the foregut. However, the mechanisms regulating this process remain unclear. In particular, the details of the human esophagus itself have been poorly researched. In this decade, studies using human induced pluripotent stem cells (hiPSCs) have proven powerful tools for clarifying the developmental biology of various human organs. Several studies using hiPSCs have demonstrated that retinoic acid (RA) signaling promotes the differentiation of foregut into tissues such as lung and pancreas. However, the effect of RA signaling on the differentiation of foregut into esophagus remains unclear. Methods We established a novel stepwise protocol with transwell culture and an air–liquid interface system for esophageal epithelial cell (EEC) differentiation from hiPSCs. We then evaluated the effect of all-trans retinoic acid (ATRA), which is a retinoic acid receptor (RAR)α, RARβ and RARγ agonist, on the differentiation from the hiPSC-derived foregut. Finally, to identify which RAR subtype was involved in the differentiation, we used synthetic agonists and antagonists of RARα and RARγ, which are known to be expressed in esophagus. Results We successfully generated stratified layers of cells expressing EEC marker genes that were positive for lugol staining. The enhancing effect of ATRA on EEC differentiation was clearly demonstrated with quantitative reverse transcription polymerase chain reaction, immunohistology, lugol-staining and RNA sequencing analyses. RARγ agonist and antagonist enhanced and suppressed EEC differentiation, respectively. RARα agonist had no effect on the differentiation. Conclusion We revealed that RARγ activation promotes the differentiation of hiPSCs-derived foregut into EECs.


2017 ◽  
Vol 5 (8) ◽  
pp. 1567-1578 ◽  
Author(s):  
Maureen Wanjare ◽  
Luqia Hou ◽  
Karina H. Nakayama ◽  
Joseph J. Kim ◽  
Nicholas P. Mezak ◽  
...  

Engineering of myocardial tissue constructs is a promising approach for treatment of coronary heart disease.


2009 ◽  
Vol 37 (1) ◽  
pp. 323-328 ◽  
Author(s):  
Claire M. Kelly ◽  
Stephen B. Dunnett ◽  
Anne E. Rosser

Cell-replacement therapy for Huntington's disease is one of very few therapies that has reported positive outcomes in clinical trials. However, for cell transplantation to be made more readily available, logistical, standardization and ethical issues associated with the current methodology need to be resolved. To achieve these goals, it is imperative that an alternative cell source be identified. One of the key requirements of the cells is that they are capable of acquiring an MSN (medium spiny neuron) morphology, express MSN markers such as DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa), and function in vivo in a manner that replicates those that have been lost to the disease. Developmental biology has progressed in recent years to provide a vast array of information with regard to the key signalling events involved in the proliferation, specification and differentiation of striatal-specific neurons. In the present paper, we review the rationale for cell-replacement therapy in Huntington's disease, discuss some potential donor sources and consider the value of developmental markers in the identification of cells with the potential to develop an MSN phenotype.


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