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Analyzing Embryonic Stem Cell Interaction in the Pancreas and Signaling Aspects"Literature Review" Chapter

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Embryonic Stem Cell Interaction in the Pancreas and Signaling Aspects


The mouse and human embryonic stem (ES) have the capability of differentiating themselves into Insulin-producing cells. ES cells can be induced into differentiating themselves into (IPCs) Insulin producing cells. This can be done by simply changing the culture medium, one that causes expression and dominance of the gene factor that are involved in the development of the pancreases. In some studies, the following two methods are used to differentiate the ES cells into IPCs:

Definitive endoderm formation

Embryonic body formation

The rate of spontaneous differentiation in specifically differentiated cells is always low. Thus, it is necessary that one should apply differentiation factors in selecting the lineage- specific progenitor for directed differentiation of the EC cells into the required cell type.

The differentiated cells will be obtained within 33 days. The studies show that the small molecules induce pancreatic and definitive endoderm cells in the monolayer cells in the process of differentiation. The differentiation system we used therefore represents a protocol that directs the ES cells of the mouse into the pancreatic lineage by generating IPCs. It is applicable to other strategies which makes the vitro differentiate into the insulin-producing cells (Liu & lee, 2012, p.5)

The fact that it is possible to create renewable supply of human and islet cells from a stem cell source can be used as a solution to the deficit of finding a solution for diabetic patients suffering from insulin deficiency.

The embryonic stem cells (ESCs) are a logical source of starting cells. The key reason for this is the disproportionately stable and relatively high capacity for self-renewal, which defines culture conditions and their ability to differentiate into somatic lineages. The application of development principles is key to the differentiation of hESCs into defined cell types- specifically the circuitous path into the functional b-cells. To get the function-cell, the first thing that ought to be done is to increase the efficiency including the formation of the definitive endoderm (DE) lineage required to produce the differentiated epithelium of the hind-gut, the fore and the mid-gut. They include thyroid, lung, pancreases, liver, thymus, intestine, stomach and bladder. Unfortunately, the differentiation procedure for most of the stem cell-based b-cell overlooks and ignores the basic principles of development.

It is not possible to rule out the trans-lineage differentiation to an upstream endoderm intermediate or reprogramming (direct modification) using a number of pancreases transcription factor genes. Generally, the procedures and events are unlikely to result into the production of the b-cells and maintain a stable differentiation of the islet cell function. (Baetge,2008, p.186).

Embryonic stem cells are capable of giving rise to hundreds of cell types in the human body. This brings forth prospects regenerative medicine and biomedical research. Among the diseases that have become a problem to the society are also those that include cellular deficiency diseases.

Emerging studies reveal that one can generate functional pancreatic ? cells from differentiating ESCs is not just exciting but is a guarantee that the world will soon have a new source of insulin producing cells that can be used to treat type 1 diabetes. According to this study, the endoderm is induced by sending signals to the monolayer culture that is specific to pancreatic rate using retinoic and EFG signaling and inhibition of SHH signaling. The Human ESC cells mature and generate insulin-positive cells that are transplanted using a mouse's pancreatic tissue. However, the same results cannot be achieved when transplanted with telencephalon cells or fetal liver. This suggests that there are factors in the pancreatic environment that makes the human cells to mature. (Murry & Keller, 2008, p. 673).

The benefit of ES cells is that it results in stable self-renewal and a culture of cell differentiation. This unique result that led to the invention of the tailored cell therapy that can be used to cure malignity.

The importance of using ES cells for cell therapy is that it helps to discover the protocols that direct differentiation into functional cells. This article focuses on the importance of differentiating ? cells from ES as seen via the developmental stages in the pancreatic endocrine cells, definitive endoderm, and primitive foregut/gut tube.

Considering the difficulties involved when handling human embryos and the difference between other species and human beings, differentiating human ES cells to pancrea allows for investigation of differentiating ES cells from the endoderm to the pancreases using a number of arrays proteomics (Lee & Chung,2011, p.35)

In another study, the procedure of deriving definitive endoderm cells from hESCs while culturing them in lamina circular patches of 120 ?m diameter and subsequent exposure to the keratinocyte growth, converts them into homogeneous clusters that consist of the HNF1?+ primitive tubes that look like gut cells.

In addition, the cells in these clusters could be differentiated into PDX1+/NKX6.1+ if they are exposed to additional factors. The gut tube- like clusters may be dislodged mechanically without being treated with enzymes before they are balled to form spheres of ~ 100 ?m- diameter which retains the ability of forming cells that look like pancreatic endoderm cells. This co-expresses NKX^.1, and PDX1. The size of the transplanted islets affects the secretion and the viability of the generated hESC derived pancreatic progenitors into spherical clusters that control the size of the cell number. This is a proof of the concept that contributes to the development of a renewable and long lasting treatment of type 1 diabetes (Hoof et al., 2011, p 277).

The two processes that are used in modification of chromatin are i) DNA methylation which is catalyzed by enzymes such as DNMT1 DNMT3a, DNMT3b. (ii) histone modification conducted by the Trinthorax Group proteins and (TxG) Polycomb group (PcG0) proteins. The study found that the histone modifications by the PcG Proteins were able to prevent precocious differentiation of the ES cells. The PcG play a role in the early development while the DNA is involved in the silencing of the gene in the process of cell differentiation. The chemical used in cell culture was obtained from Invitrogen (Carlsbad, CA, USA). The KINDI colonies passage was done manually at least once per week in the ratio 1:3. Subsequently, it was concluded that the differentiation resulted in the generation of the pancreatic lineage cells. (Pethe, Nagvenker & Bhartiya,20 14, p.2).

The pancreatic islets in all mammals develop through commitment of the foregut endoderm characterized by expressing the lineage restricted transcription factors including the protein-based peptide YY, pancreatic duodenal homeobox 1 (PDXI) and islet amyloid polypeptide (IAPP) and pancreatic polypeptide (PP). Other studies had demonstrated that ES cells are capable of being committed towards embryonic endoderm lineages such as liver, gut and pancreatic islet endocrine cells. PDX1 and YY are important in the development. Very little data is available on the co-expression of the markers during the embryogenesis. The finding of this study was demonstrated in the YY expression in PDX1+ cells. Other studies had shown that within the pancreatic bud epithelium, the expression of the YY is limited to the endocrine cell pool and will not overlap the YY+ and PDX1 + cells which was identified before the positive cells hormone were elaborated. The expressing subset gave clues to the differentiation of the committed PDX1+ epithelial progenitors (Kahan et al., 2003, p.2022)

This explains the main signal that operates during pancreatic epithelium expression in the embryo of a mouse. Newer methods have been devised to help generate PDX1 progenitors from PSC in- vitro. It involves combination of a number of factors and treatment timing. The method used in generation of the pancreatic progenitors is capable of maturation to form glucose responsive cells in vivo. The ideal condition was identified and the generation of progenitors such as progenitors from PSC lines was identified.

When the optimal conditions defined in stage 4 cells (protocol P-5) were used it was found that tetratomic were formed after grafting in the immunocompromised mice (data is not available). From this, the authors suggest that alternative for therapeutic approaches (cell based) to type 1 diabetes may be used to define the conditions that can be used to capture and stabilize the expansion of pancreatic progenitors ( Rostovskaya, Bredenkamp, & Smith, 2015, p.7)

According to another study in which the pancreatic IPCs were generated via dual hESC lines, YT2 or YT1 optimized the differentiation procedure with in a chemically cultured structure. Around 5-7 x 106 cells (differentiated) had been transplanted into a fat pad of epididymal of involving ScID/NOD mice (n = 20). Moreover, the control group then transplanted hESCs (n=6). Subsequently, the graft survival function had been assessed utilizing the immunohistochemistry and then the human C-peptide along with levels of blood glucose were measured. The results obtained showed that the pancreatic IPCs had been produced in four stage differentiated protocols using the hESCs. The (SCs) stem cells have regenerated and immunological properties that could be harnessed to be used to treat type 1 diabetes (Hua et al., 2014, p. 7).

Recent reports indicate that there… [END OF PREVIEW]

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