Induced Pluripotent Stem Cells and Cloning

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Questions and Answers

What is one of the main issues researchers face with induced pluripotent stem cells (iPSC)?

High production cost

Lack of available data

Excessive mutation rates (correct)

Insufficient ethical guidelines

Which of the following is NOT a roadblock in whole organism cloning?

High efficiency rates (correct)

Decreasing efficiency

Technical problems

Political and ethical issues

What is the primary purpose of therapeutic cloning?

To create genetically modified organisms

To extract embryonic stem cells for medical use (correct)

To clone entire humans for research

To clone pets for companionship

What was a significant outcome of Dr. Hwang Woo-suk's research on human embryos?

Retraction due to fabricated results Signup and view all the answers

Which of the following gene factors is sought to improve the use of iPSC?

Replacing cMyc with safer gene substitutes Signup and view all the answers

What is a key limitation of transgenic modification discussed in the content?

Unpredictable insertion sites and associated risks Signup and view all the answers

Which significant cloning project is mentioned as having implications for our understanding of cloning?

Newcastle University’s human embryonic clone Signup and view all the answers

Which ethical consideration is integral to stem cell research?

Consent from human subjects Signup and view all the answers

What was the outcome of the adenovirus trial conducted on Jesse?

Patient died from an immune reaction to the virus Signup and view all the answers

Which patient first underwent successful gene therapy for SCID?

Ashanthi DeSilva Signup and view all the answers

What is a major concern in gene therapy trials for SCID patients?

Risk of developing oncogenic diseases Signup and view all the answers

What was notable about the SCID trials involving ADA-SCID?

No leukemia cases were reported Signup and view all the answers

What is one hurdle in current gene therapy technologies?

Delivery mechanism of the DNA Signup and view all the answers

What is the purpose of the ACT trial mentioned in the content?

To test hESC-derived retinal cells for treating Stargardt Macular Dystrophy Signup and view all the answers

What was a reason for halting some MD trials in 2017?

A patient developed a membrane over the eye Signup and view all the answers

When was the Phase I clinical trial with ViaCyte beta cells approved?

August 2014 Signup and view all the answers

Which of the following genes is NOT one of the reprogramming factors identified in the generation of iPSCs?

TP53 Signup and view all the answers

What was one of the methods used to detect the induction of pluripotent state in somatic cells?

Resistance to a drug Signup and view all the answers

Which of the following results suggest that iPSCs are capable of forming all three germ layers?

Formation of induced teratomas Signup and view all the answers

What role does c-Myc play in the reprogramming of somatic cells?

It aids in overriding induced senescence Signup and view all the answers

What is the primary efficiency rate of cells becoming iPSCs during reprogramming?

< 1% Signup and view all the answers

Which of the following is NOT a proof of iPSCs being true stem cells?

Expression of tumor markers Signup and view all the answers

Which of the following factors is considered to have the least impact on colony formation when removed from the 10 identified factors?

c-Myc Signup and view all the answers

What ethical concern is most commonly associated with stem cell research?

Potential for human cloning Signup and view all the answers

Which application of human iPSCs shows promise in regenerative medicine?

Tissue engineering Signup and view all the answers

What is the main importance of embryoid body formation in iPSC research?

It indicates pluripotent capability. Signup and view all the answers

Study Notes

Induced Pluripotent Stem Cells (iPSC)

iPSC generated by Takahashi et al., 2006-2007, won the Nobel Prize
Reprogramming factors for creating iPSC: OCT4 (O), SOX2 (S), KLF4 (K), cMYC (M) also known as OSKM
Reprogramming is extremely inefficient, less than 1% of cells become iPSC cells
cMyc helps override the tumour suppressor gene barrier and induced senescence during reprogramming

Challenges and Concerns

iPSC generation: Search for less carcinogenic gene sets, non-genetic factors, and alternative genes for cMyc
iPSC efficiency: Increasing production efficiency and reducing mutation rates
Ethical and political considerations: Roadblocks to whole organism cloning, including technical limitations, declining efficiency, and ethical conflicts.

Whole Organism Cloning

Dolly the sheep (1997): Cloned from an adult mammary gland cell, lived to six years old and had offspring
Human embryonic clone (Newcastle University, UK): Clones survived only a few days without producing stem cells.
Cloning of primate embryos (2007): Novel DNA extraction method used for successful cloning.
Pyrenean ibex (2009): Extinct form of goat cloned by Spanish scientists. Died shortly after birth due to lung defects.
Human cloning: 2004, S.Korean Group claimed to clone human embryos and extract stem cells. The claim was later retracted due to fabrication.

Therapeutic Cloning

Extract nucleus from a patient's somatic cell and implant into an egg.
Stimulate cell division to form a blastocyst.
Extract embryonic stem cells and form cell lines.
Infuse ESC line or differentiated tissue into the patient.

Gene Therapy

Goal: Alter genome to correct disease errors in cells or whole organisms.
Potential applications: Understanding gene importance in regeneration.
Limitations: Uncontrollable gene insertion sites, epigenetic modification of promoters over time.
Jesse's form (1990): Controllable with diet and medication, a trial using adenovirus to correct the gene resulted in the patient's death due to an immune reaction.
SCID trials: Deficiency in B/T cells, patient Ashanthi DeSilva (1990) was the first to undergo successful gene therapy.
Leukemia risk: A gene inserted near an oncogene in a SCID trial led to leukemia in 10 patients. ADA-SCID trials did not involve oncogenic genes and no leukemia cases were reported.
Gene therapy success: Since 1999, gene therapy has restored the immune systems of at least 17 children with ADA-SCID and X-SCID.

Challenges in Gene Expression Manipulation

Delivery mechanism of DNA.
Efficiency of delivery.
Stability of the delivered DNA.
Safety of stable integration.

Current State of Stem Cell Therapies

Recognition of importance - clinical, research, and drug testing - at public and government levels.
High scientific rigor required for research.
First approved hESC clinical trial (2009).
Economic factors hindering embryonic stem cell therapy (2011).

Current hESC Trials in the US

ACT trial: Testing safety of hESC-derived retinal cells for Stargardt Macular Dystrophy (SMD).
Second ACT trial: Testing safety of hESC-derived retinal cells for age-related macular degeneration.
MD trials stopped in 2017 due to a membrane developing over a patient's eye.
Phase I/II clinical trials involving hESC-derived retinal pigment epithelial (RPE) cells approved for severe myopia (2013).

Diabetes Trial

Phase I clinical trial, approved in 2014, for ViaCyte beta cells from hESCs.
Trial results indicated the therapy was safe and tolerable.
Animal models demonstrate regeneration within months.

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Description

This quiz explores the concepts of induced pluripotent stem cells (iPSC) including their creation, challenges, and ethical concerns. It also covers the historical context of whole organism cloning, such as Dolly the sheep. Test your knowledge on the advancements and implications of stem cell research and cloning technologies.