Overview:
• Somatic cell nuclear transfer (SCNT) is a cloning procedure carried out in a lab. In this
procedure, an egg cell that has had its own nucleus removed receives the nucleus of a
somatic cell (a body cell). After then, the newly formed cell is encouraged to start
dividing and turning into an embryo.
• Since the resultant embryo is genetically identical to the somatic cell donor, SCNT is a
type of cloning. This process has been used to create clones in animals, including Dolly
the sheep, and it may also have uses in human health.
• For instance, SCNT may be utilised to create embryonic stem cells that are genetically
similar to a patient and subsequently be employed for regenerative therapy without the
threat of immune system rejection.
• The use of cloned embryos for research and other purposes creates ethical questions,
making SCNT a contentious procedure. There are limitations on using SCNT for
research purposes in several nations, including the US.
Procedure:
• The first step in the SCNT procedure is to get an egg cell from a donor animal, like a
cow or sheep. A specialised micropipette is then used to enucleate, or remove, the egg
cell's nucleus.
• The donor cell is then decided to be a somatic cell. This may be a cell from the
animal's skin or muscular tissue, for example. The somatic cell's nucleus is then taken
out using a similar micropipette.
• The donor nucleus and the enucleated egg cell are then fused together using a little
electrical charge. Reconstructed embryo is the name given to the resultant cell, which
has the cytoplasm of the egg cell and the nucleus of the somatic cell.
• The recreated embryo is then nurtured in the laboratory for a while so that it can mature
into a blastocyst, which is an embryonic stage that is early in development.
• Depending on the objectives of the research, the blastocyst can now be employed for a
number of things. For instance, the blastocyst may be utilised to produce embryonic
stem cells, which can later be used to drug development or regenerative medicine.
• SCNT has been used to create clones of animals like Dolly the sheep. Due of ethical
concerns, SCNT is not being applied to human reproductive cloning.
• The generation of embryonic stem cells that are genetically similar to a patient, which
may subsequently be employed for regenerative therapy without running the risk of
immune system rejection, is one prospective use of SCNT in human medicine.
Applications of SCNT:
• Sheep, cows, and pigs have all been successfully produced as clones via SCNT.
However, primates and other animals have had less success with the strategy.
• The use of SCNT to create patient-specific embryonic stem cells that might be
employed for therapy has potential uses in regenerative medicine. As an illustration,
SCNT might be used to create embryonic stem cells that can develop into heart muscle
cells, which could subsequently be utilised to heal the damaged tissue in a patient with
a damaged heart.
• SCNT may potentially be utilised to research diseases and provide brand-new
treatments. Researchers might investigate the effects of various genetic mutations or
environmental variables on illness onset and progression by developing genetically
identical embryos. This could make it possible to find new pharmacological targets or
create more potent therapies.
• SCNT has also been suggested as a means of protecting threatened species.
Researchers may be able to preserve these species' genetic variety and avoid
extinction by utilising SCNT to produce embryos from the cells of threatened species.
• In certain instances, SCNT has been utilised to create genetically altered animals for
study. In order to make the recreated embryo, the somatic cell's DNA must first be
altered. However, this strategy poses ethical questions about the development and
application of genetically engineered animals.
Applications of AI in SCNT:
• Quality control: Controlling the quality of the regenerated embryos is one of the main
difficulties in SCNT. AI might be used to examine photos of the rebuilt embryos and
find any anomalies or flaws that would lower the procedure's success rate. This may
make it easier for scientists to choose only the healthiest embryos for continued
development.
• Optimization: The timing and length of the electrical pulses used to fuse the egg and
donor cells might all be optimised using artificial intelligence (AI). AI may be able to
assist researchers in determining the procedure's most successful settings by
analysing data from earlier efforts.
• Gene editing: AI might be used to direct tools for gene editing, such CRISPR, to
precise places in the donor cells' genome. This would make it possible to accurately
modify the donor cells' genomes before using them for SCNT, thereby increasing the
procedure's success rate.
• Prediction modelling: AI might be used to create prediction models that gauge the
success rate of SCNT in light of a variety of factors, including the donor animal's age
and health, the type of donor cells utilized, and the circumstances surrounding the
surgery. This could aid in procedure optimisation and the choice of the most suitable
donor cells.
Evidence based articles and links:
• “Somatic cell nuclear transfer: Past, present and future perspectives”: https://
pubmed.ncbi.nlm.nih.gov/17610946/
• “A background to nuclear transfer and its applications in agriculture and human
therapeutic medicine”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570687/
• “Somatic Cell Nuclear Transfer Reprogramming: Mechanisms and Applications”:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173619/
• “Stem cell therapies and benefaction of somatic cell nuclear transfer cloning in
COVID-19 era”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114669/
• “Strategies to Improve the Efficiency of Somatic Cell Nuclear Transfer”: https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC8879641/
• “DeepNEU: cellular reprogramming comes of age – a machine learning platform with
application to rare diseases research”: https://ojrd.biomedcentral.com/articles/10.1186/
s13023-018-0983-3
iPSC's - Induced pluripotent stem cells
Adult cells, including skin or blood cells, may be reprogrammed to become pluripotent
stem cells, which allows scientists to create induced pluripotent stem cells (iPSCs), a
particular form of stem cell. In a manner similar to embryonic stem cells, this implies that
they can develop into any form of cell in the body.
Overview:
• History: Shinya Yamanaka, a Japanese researcher, originally developed iPSCs in 2006.
He found that by introducing particular genes into adult cells, he could reprogramme
them into a pluripotent state.
• Reprogramming: To guarantee that adult cells are entirely pluripotent, a sequence of
procedures must be taken throughout the process of reprogramming adult cells into
iPSCs, which can take many weeks.
• Advantages: As was already established, iPSCs are superior to embryonic stem cells
in a number of ways. They may, for instance, be produced using the patient's own
cells, lowering the possibility of transplant-related rejection. Additionally, they do not
result in the killing of embryos, which some individuals find makes them more ethically
acceptable.
• Limitations: Although iPSCs offer a lot of potential for regenerative medicine and drug
development, their usage is currently constrained in key ways. One issue is that the
reprogramming procedure has the potential to cause cell mutations, which may have
unforeseen effects. iPSCs may not always behave like naturally occurring cells and
might be challenging to develop into specific cell types.
• Applications: The study of human development, disease modeling, drug screening,
and regenerative medicine are just a few of the scientific fields where iPSCs are being
employed. They have the potential to transform medicine by offering fresh approaches
to ailments and wounds that were formerly believed to be incurable.
Procedure:
• Collecting source cells: Collecting the adult cells that will be reprogrammed is the
initial step in creating iPSCs. These cells may originate from skin cells, blood cells, or
other cell types, among other sources.
• Reprogramming factor introduction: The adult cells are then cultivated in the lab and
exposed to reprogramming factors, which are frequently pluripotency-maintaining
genes including OCT4, SOX2, KLF4, and c-MYC. Typically, a viral vector is used to
deliver these genes into the cells, integrating them into the DNA of the host cell.
• iPSC cultivation and selection: After the reprogramming factors are added, the cells
are cultivated in a lab environment that encourages pluripotency. Some of the cells will
eventually start to show pluripotent stem cell traits. Then, these cells are chosen for
additional cultivation and development.
• Characterization of iPSCs: To make sure that the iPSCs produced are entirely
pluripotent and are not contaminated with other cell types, they must be characterised.
Usually, a combination of genetic and functional tests is used to do this.
• Differentiation of iPSCs: The ability to develop iPSCs into a number of cell types, such
as neurons, heart cells, and liver cells, is the last advantage of this technology.
Numerous methods, including genetic modification and chemical induction, can be
used to accomplish this.
Applications of AI in iPSC’s:
• Quality control: AI may be used to analyse huge datasets of iPSCs and find changes
in purity and quality as part of quality control. This can assist researchers in
streamlining the reprogramming procedure and guarantee that the iPSCs that arise are
of good quality and appropriate for use in subsequent applications.
• Differentiation Protocols: AI may be used to create and improve differentiation
methods that divide iPSCs into distinct cell types. Large datasets of gene expression
and cellular behaviour may be analysed by AI algorithms to pinpoint the crucial
variables that influence differentiation and to hone methods for increased effectiveness
and repeatability.
• Drug discovery: Using AI, a huge library of substances may be screened to see how
they affect iPSC-derived cell types. AI algorithms may find substances that have the
potential to treat particular diseases or disorders by analysing gene expression and
cellular activity, and they can assist researchers in the development of novel medicines.
• Disease modelling: Using AI, massive datasets of iPSCs from individuals with
particular illnesses or disorders may be analysed. AI algorithms can find variations in
gene expression and cellular behaviour that could contribute to the disease by
contrasting these iPSCs to healthy controls, which will aid researchers in creating novel
medicines.
• Personalized medicine: iPSCs from individuals with particular genetic backgrounds or
disease states may be analysed using AI on sizable datasets. AI algorithms can assist
researchers in creating personalised treatments that are catered to the unique patient
by locating genetic and epigenetic markers linked to certain diseases.
Evidence based articles and links:
• "Induced pluripotent stem cell technology: a decade of progress”. Link: https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC6416143/
• "Induced pluripotent stem cells: advances to applications”. Link: https://
pubmed.ncbi.nlm.nih.gov/21165156/
• "Recent advances of induced pluripotent stem cells application in neurodegenerative
diseases”. Link: https://pubmed.ncbi.nlm.nih.gov/31255650/
• "Current status and future directions of clinical applications using iPS cells-focus on
Japan”. Link: https://pubmed.ncbi.nlm.nih.gov/34407307/
• "Induced Pluripotent Stem Cells: A New Frontier for Stem Cells in Dentistry”. Link:
https://pubmed.ncbi.nlm.nih.gov/26285811/
• "Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical
Applications in Cancer”. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3830845/