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Induced Pluripotent Stem Cells(iPS Cells)

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Tahmina Siddiqi

on 11 April 2015

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Transcript of Induced Pluripotent Stem Cells(iPS Cells)

Induced Pluripotent Stem Cells(iPS Cells)
A cell's ability to develop and differentiate into any cell type
Embryonic/Placental Cells
What does it mean to be Pluripotent?
Cloning Used to Make Stem Cells from Adult Humans
By Elizabeth Landau, CNN
• IPS cells derived in vivo share similarities to those that would’ve been obtained by embryonic stem cells.
• They are capable of producing embryo like structures, if they are capable of trophectoderm lineage differentiation and produce totiprotent stem cells like ES cell. They are essentially different from IPS cells derived in vitro.
• Ethical values come to question if IPS cells in vivo, may violate the concept of moral issues as it may have the potential of becoming a human.

In Vivo IPS
• IPS cells may lead eventually to reproductive cloning, especially if embryos may be obtained with tetraploid complementation.
• Although, they avoid the controversy of not being derived from embryos.
• The creation of cells should lack the ability to develop, and won’t be able to develop into a human being.
Viable Embryos
• Although not similar to ES cells that may lead to exploitation of women for their ova, iPS cells are still under the possibility of being patented.
• Such would make somatic cells to be thought to have value and be used towards profits for iPS research.

What do we think?
What are Stem Cells?
How does it work?
All cells contain the genes for pluripotency
These genes are turned off in adult cells.
It is not known how these genes are turned on.
How do you induce these genes?
Embryonic cells would no longer be needed.
Drugs can be tested in-vitro to determine the effect of it on human's, reducing the need for human test subjects.
With further research, iPS cells can be aimed to differentiate into particular cells.
iPS cells can be used to study early development in humans, which could lead to discoveries in cell therapy for auto-immune disease.
Active research is being conducted in generating tumor-free iPS cells.
Further research into iPS cells could hold the key to understanding more about development of diseases by observing how the cells behave.
It's too early to be against it
The possibilities are endless
Growing organs
Treating diseases
The cells that are created are perfectly matched to the patients that need them.
Cells would be genetically identical to patient's
They could allow for a limitless supply of tissues to be used for medical purposes. Because the induced pluripotent stem cells are able to form any of the three germ layers there is the possibility to have them form any type of tissue found in the body.
Non-viruses to reprogramming in the somatic cell show fewer abnormalities in the cell.
The induced pluripotent stem cells can eventually be used to learn more about disease by reproducing the disease to be studied and test possible treatments on it. They can also be used to form tissues and blood cells to be used for transplants without worries of the body destroying it.
No destruction of normal human blastocyst is required

Study by Okamoto and Takahashi
produced iPS cells from monkeys to see their ability to differentiate into retinal cells.
(Monkey cells to iPS cells)
Fibroblasts from cynomolgus monkey abdominal cells were infected with retroviruses (Oct ¾, Sox 2, Klf4, and c-Myc).
Six days after infection, fibroblasts were transferred into mitomycin C-treated STO feeder layers.
Next day, culture medium was changed into primate cell medium containing basis FGF with valproic acid.
One month after viral infection, iPS cells colonies appeared similar to embryonic stem cells.

Morphology of colonies of monkey iPS cell lines and ES cell lines
The cells were then transferred for expansion

(iPS cells to Differentiated Cells)
The iPS cells were dissociated with trypsin and collagenase IV
The dissociated cells wre transplated into the SCID mice.
After 2-3 months of transplantation, cells line was tested.

Confirmation of Differentiation
The injected cells formed teratomas.
The teratomas formed were sectioned and stained with hematoxylin-eosin for visualization of tissues.

Risk for First-in-Human Trials
• Switching from animals to humans testing three criteria should be addressed;
Internal validity measures the methodical of pre-clinical animal testing.
External validity selection of animal models that most accurately represents the human disease.
Correspondence where the animal testing and first-human trial in protocol and parameters should match.

• Patients that are subjects for research should not face risks that are greater than future benefits.
• Direct benefit would be hard to measure as the first trials are used with doses that wouldn’t produce therapeutic effect.
• It’s very difficult to focus on the interest of a patients compared to search for epistemic and clinical benefits of the broader medical field.
• For risk-management looking at just ethical point of view is not enough, there is also the medical point of view.

• There are possibilities that the use of cell replacement or iPS cells transplantation may lead to irreversible risks.
• The possibility of the iPS cells that are differentiating to migrate to unwanted sites.
• In treatment of Neurological diseases the central nervous iPS cells may not only interfere with physical but cognition, emotion, and personality.
• The use of suicide cells may be away to reduce such complications. This areas needs much development.

Viral Vectors
• For the placement of reprogrammed iPS cells, viral vectors are used as the delivery mechanism.
• Pluripotent cells may lead to iatrogenic cancer.
• This may lead to genetic defects.
• The development of viral free vectors that can still induce somatic cells. Virus-free vectors that can be removed or protein factors may lower the safety concern.
• However, new methods offer reduction of efficiency and decrease the rate of reprogramming.
• Non carcinogenetic methods of Sox2, Klf4, c-Myc offer a way, with the negative aspect of having partially reprogrammed somatic cells.
• C-Myc may be p53 suppressor at cell cycle checkpoint.
• Germline alternations that may possible be carried to the next generation, and the affect is unknown.

Availability of iPS Therapies
• Production of cells for individual patient needs will be costly and time consuming.
• hiPS cell therapies need a health care system that can produce and distribute them with efficiency.
• It may not be distributed to countries that view such methods immoral.
• If they may be derived from umbilical chord blood, or such it may be available at high quantities.
Look out for...
What it means to be Pluripotent
Atleast four Pluripotency genes
Major challenge associated with iPS cells
Conclusion from the Study

The study showed successful transformation of epithelial cells into Retinal Pigment Epithelial Cells.
To further validate the results from the study, researched should test the possibility of immune rejection. "
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