Podcast
Questions and Answers
What type of stem cells are capable of giving rise to all cell types except for those of the placenta?
What type of stem cells are capable of giving rise to all cell types except for those of the placenta?
Which type of stem cells were first isolated at the University of Wisconsin in 1998?
Which type of stem cells were first isolated at the University of Wisconsin in 1998?
What is a major disadvantage of embryonic stem cells?
What is a major disadvantage of embryonic stem cells?
Which statement about adult stem cells is true?
Which statement about adult stem cells is true?
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What advantage does somatic cell nuclear transfer (SCNT) offer for stem cell research?
What advantage does somatic cell nuclear transfer (SCNT) offer for stem cell research?
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What is the primary characteristic of stem cells?
What is the primary characteristic of stem cells?
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Which of the following processes describes how cells become specialized?
Which of the following processes describes how cells become specialized?
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Which human clinical need is NOT mentioned as requiring stem cell therapies?
Which human clinical need is NOT mentioned as requiring stem cell therapies?
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What happens to the regenerative ability of an organism as its complexity increases?
What happens to the regenerative ability of an organism as its complexity increases?
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During which stage of development do cardiac muscle cells and neurons differentiate?
During which stage of development do cardiac muscle cells and neurons differentiate?
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What is the term for transferring cells from one culture dish to another?
What is the term for transferring cells from one culture dish to another?
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What type of regenerative ability does the planarian exhibit?
What type of regenerative ability does the planarian exhibit?
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Which of the following best describes adult stem cells?
Which of the following best describes adult stem cells?
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What is the main characteristic of epimorphic regeneration?
What is the main characteristic of epimorphic regeneration?
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What type of cells are primarily responsible for regeneration in planaria?
What type of cells are primarily responsible for regeneration in planaria?
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Which type of regeneration is characterized by the regeneration of new individuals from body pieces?
Which type of regeneration is characterized by the regeneration of new individuals from body pieces?
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In vertebrates, which of the following structures is primarily formed during the regeneration of the tail in amphibians?
In vertebrates, which of the following structures is primarily formed during the regeneration of the tail in amphibians?
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What distinguishes morpholaxis from other types of regeneration?
What distinguishes morpholaxis from other types of regeneration?
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Which type of regeneration occurs after total or partial amputation of an organ?
Which type of regeneration occurs after total or partial amputation of an organ?
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Which animal is mentioned as an example of morpholactic regeneration?
Which animal is mentioned as an example of morpholactic regeneration?
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What is a key feature of the regenerated tail in reptiles, such as lizards?
What is a key feature of the regenerated tail in reptiles, such as lizards?
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What is the main advantage of using umbilical cord stem cells over bone marrow stem cells?
What is the main advantage of using umbilical cord stem cells over bone marrow stem cells?
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Which of the following is NOT one of the important functions of umbilical cord stem cells?
Which of the following is NOT one of the important functions of umbilical cord stem cells?
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What is the percentage of serious Graft versus Host Disease (GVHD) occurrence in unrelated bone marrow transplants?
What is the percentage of serious Graft versus Host Disease (GVHD) occurrence in unrelated bone marrow transplants?
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What does the term 'homing' refer to in the context of umbilical cord stem cells?
What does the term 'homing' refer to in the context of umbilical cord stem cells?
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How do umbilical cord stem cells compare to fetal lymphocytes in terms of HLA compatibility?
How do umbilical cord stem cells compare to fetal lymphocytes in terms of HLA compatibility?
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What is the main reason for lower incidence of Graft versus Host Disease (GVHD) in umbilical cord blood transplants?
What is the main reason for lower incidence of Graft versus Host Disease (GVHD) in umbilical cord blood transplants?
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Which type of stem cell is primarily isolated from umbilical cord blood?
Which type of stem cell is primarily isolated from umbilical cord blood?
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What does somatic cell nuclear transfer (SCNT) mainly involve?
What does somatic cell nuclear transfer (SCNT) mainly involve?
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Which type of regeneration involves the dedifferentiation of adult structures to form an undifferentiated mass of cells?
Which type of regeneration involves the dedifferentiation of adult structures to form an undifferentiated mass of cells?
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What is the term used to describe the regeneration of a different organ from the one that was removed?
What is the term used to describe the regeneration of a different organ from the one that was removed?
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During which stage of limb regeneration does the bulge known as blastema form?
During which stage of limb regeneration does the bulge known as blastema form?
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In which type of regeneration do additional heads develop after a deep incision in organisms like planaria?
In which type of regeneration do additional heads develop after a deep incision in organisms like planaria?
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Which of the following best describes morphallaxis in regeneration?
Which of the following best describes morphallaxis in regeneration?
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What is the final stage of limb regeneration in salamanders called?
What is the final stage of limb regeneration in salamanders called?
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What happens to cells in the regeneration bud during epimorphosis?
What happens to cells in the regeneration bud during epimorphosis?
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What characterizes the regeneration mechanism in shrimp, specifically Palinurus?
What characterizes the regeneration mechanism in shrimp, specifically Palinurus?
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What can be regenerated from a small fragment in hydra or planaria?
What can be regenerated from a small fragment in hydra or planaria?
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Which type of regeneration is characterized by significant new growth and development?
Which type of regeneration is characterized by significant new growth and development?
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In which group of animals is regeneration power most prominent in the larval stages?
In which group of animals is regeneration power most prominent in the larval stages?
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What kind of regeneration ability do lizards exhibit?
What kind of regeneration ability do lizards exhibit?
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Which of the following is true about the regeneration capabilities of mammals?
Which of the following is true about the regeneration capabilities of mammals?
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Which group of animals typically exhibits the highest regenerative capability, particularly in the liver?
Which group of animals typically exhibits the highest regenerative capability, particularly in the liver?
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What form of regeneration involves remodeling of existing tissues with little new growth?
What form of regeneration involves remodeling of existing tissues with little new growth?
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Which of the following is NOT true regarding the regeneration process in various animal groups?
Which of the following is NOT true regarding the regeneration process in various animal groups?
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Study Notes
Education & Work Experience of Dr. Shamsul Azlin Bin Ahmad Shamsuddin
- 1987-1989: A.S.A.S.I. sains
- 1989-1993: BSc Zoology
- 1993-1997: MPhil, UM
- 1997-2000: Embryologist, Pantai Bangsar Medical Centre
- 2000-2003: Embryologist, Gleaneagles, Ampang Medical Centre
- 2003-2006: Embryologist, Damansara Specialist Hospital
- Oct 2006- June 2011: PhD, Sheffield University, UK
- 1997: Embryologist training, Melbourne, Australia (2 months)
- 2000: Embryologist training, Cairns, Queensland, Australia (2 weeks)
- 2003: Embryologist training, NUS, Singapore (3 days)
Embryologist Locums
- Sime Darby Medical Centre, Subang Jaya
- Metro Hospital, Kelang
- Gleaneagles, Penang
- Darul Ehsan Medical Centre, Shah Alam
- Mahkota Medical Centre, Melaka
- LPPKN, KL
- Columbia Asia Hospital, Setapak, KL
- Prince Court Hospital, KL
Regeneration in Nature
- Planarian
- Crayfish
- Embryos
Inverse Relationship
- Increase complexity
- Decrease regenerative ability
Regeneration in Humans
- High: Skin, Liver, Muscles, Gut Lining
- Moderate: Bone
- Low: Heart, Brain, Joints (Knee)
Clinical Needs for Stem Cells in Humans
- Cardiovascular: Myocardial infarction, Stroke
- Bone: Non-union fractures, Tumor resections
- Nervous: Spinal Cord Injury, Degenerative diseases
Definitions of Stem Cells and Differentiation
- Stem cells: Undifferentiated cells that divide indefinitely in culture (self-renew) to become specialized cells
- Differentiation: The process where cells become specialized
- Stem cells with decreasing potential (Adult stem cell): No longer capable of cell division
- Cardiac muscle cells, Neurons produced during embryonic development, differentiate, and retained through life
Cell Differentiation Diagram
- Pluripotent stem cell (Embryonic stem cell)
- Multipotent stem cells (Adult stem cell)
- Differentiated cells (muscle, nerve, skin, fibroblast, etc.)
Types of Stem Cells
- Embryonic Stem (ES) Cells
- Embryonic Germ Cells
- Adult Stem Cells
- Umbilical Cord-Blood Stem Cells
- Somatic Cell Nuclear Transfer (SCNT)
- Induced-Pluripotent Stem (iPS) Cells
Embryonic Stem Cells Details
- Embryos are from in vitro fertilization (IVF)
- Cells are taken from the Inner Cell Mass (ICM) of a blastocyst.
- ICM cells are nourished in a petri dish in an incubator.
- Cells are given different types of factors/chemicals to differentiate.
- These cells can give rise to most types of cells.
- Human embryonic stem cell lines were first derived in 1998 by Dr. James Thompson.
Stem Cell Capacity
- Embryo
- Inner cell mass
- Broad capacity
Somatic Cell Nuclear Transfer (SCNT)
- Creates clones for reproductive and therapeutic reasons.
- The diagram shows the removal of the donor nucleus from a somatic cell for the schematic purposes (In general, the whole donor cell is usually transferred).
Induced Pluripotent Stem Cells (iPSCs)
- Mature somatic cells were genetically engineered by viruses to achieve pluripotency (ES-like state) in 2007
- Forced expression of genes helped reprogram adult mouse/human cells into pluripotency
- Strategies were developed to deliver genes (e.g., non-integrating viruses, chemicals, small molecules) to prevent harmful changes
- This method allows for patient-specific cell therapies avoiding immune rejection after transplantation
Stem Cells Research in Malaysia
- Haematopoietic stem cells (UKM)
- Mesenchymal stem cells (IMR & UMMC)
- Tooth pulp stem cells (Dental, UMMC)
- Bone marrow stromal stem cells (also known as mesenchymal stem cells or skeletal stem cells)
Cord Blood versus Bone Marrow
- Cord Blood: Collection non-invasive, painless, no donor risk. Greater HLA compatibility due to decrease fetal lymphocyte functionality. Graft versus Host Disease (GVHD) reduced to 10% due to the absence of antibodies in the stem cells. Units are processed and ready for transplant. Significantly less expensive.
- Bone Marrow: Collection is invasive, painful. Must be performed in a hospital surgical setting. Stem cell maturity requires a greater HLA match to perform a transplant. Serious GVHD occurs in 60% of all unrelated Bone Marrow transplants. Bone Marrow is donor-dependent.
Stem Cell Capacity Chart
- Embryo (Broad)
- Fetus
- Adult Organism (Limited)
Epigenetics Summary
- Epigenetics literally means "above" or "on top of" genetics.
- It refers to external modifications to DNA that turn genes "on" or "off".
- These modifications do not change the DNA sequence.
- They affect how the cells "read" the genes.
- Heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence: a change in phenotype without a change in genotype. -Epigenetic change is a regular and natural occurrence but can also be influenced by factors like age, environment/lifestyle,and disease state.
- Epigenetic modifications can manifest in many ways, such as terminal differentiation of cells into skin, liver, and brain cells.
Mechanisms of Epigenetics
- DNA Methylation
- Histone Modification
- Non-coding RNA (ncRNA) associated genes
Terminology of Potential (Plasticity)
- Totipotent
- Pluripotent
- Multipotent
- Unipotent
What makes stem cells pluripotent?
- Receptors on their surface that make them responsive to signals from their environment (the niche)
- Low levels of gene expression for cell types, (e.g., bone, fat, muscle, cartilage).
- Genes packaged into active and inactive segments
- Active genes: open configuration (accessible)
- Inactive genes: closed configurations (inaccessible)
- Inactive genes with the potential for activation (open configuration but with a brake on)
Early Development
- Signals come from within cells and neighboring cells.
- Maternal nutrition is important for fetal development.
- Maternal stress hormones can affect the fetus.
After Birth and Continuing Life
- Variety of environmental factors shape the epigenome.
- Social interactions, activity, and diet generate signals that travel throughout the body.
- Signals within the body are important for many processes including growth and learning.
- Hormonal signals trigger puberty-related changes.
Even Into Old Age
- Cells continually respond to environmental signals.
- Environmental signals trigger changes in the epigenome.
- Cellular signals direct body maintenance processes.
- Re-establishment of cellular maintenance processes is similar to embryonic development.
The Epigenome Program
- Programmed alterations of histone patterns.
- Starts in egg cells, affecting differentiated skin/liver cells.
Comparison of Embryonic and Adult Stem Cells
- Adult Stem Cells: From mature tissues; umbilical cord and placenta
- Embryonic Stem Cells: From inner cell mass of a blastocyst
- Multipotent vs Pluripotent and Isolation times
- Further analysis of human tissue responses
iPSCs—The Wave of Future
- iPSCs are regarded as innovative stem cell research.
- Research on disease models, drug screening, and toxicology testing
- Generating patient-specific cells, allowing unprecedented access to human biology.
- Studying development and function of human tissues, and regenerative medicine.
iPSC Applications
- Treating Parkinson's Disease via cell replacement therapy.
- Creating electrically active neurons, for studying and treating neurological disorders.
- Regenerating beta cells (for diabetes)
- Creating mouse kidneys, (Hiromitsu Nakuchi)
iPSC Limitations
- DNA methylation errors compared to ESC lines.
- Unable to create viable chimeras.
- Some factors such as c-Myc are oncogenic.
iPSC Complications
- Potential tumor formation due to viral transfection systems.
- Successful use of adenovirus (Konrad Hochedlinger) for gene delivery to eliminate tumor formation risk.
Cloning Types
- Reproductive Cloning: Creating identical individuals
- Therapeutic Cloning: Cloning embryos for research; never implanted
- This is used for drug designing, disease modeling and in regenerative medicine.
Animal Models of Regeneration
- Hydra: Regenerates every part of the body.
- Planaria: Contains neoblast cells.
- Annelids: Formation of blastema (cells under the wound or severed area).
Regeneration of Vertebrates and Types of Regeneration
- Fish, amphibians, reptiles can regenerate.
- Regeneration power is well-marked in urodel amphibians (salamanders, and newts).
- Lizards exhibit autotomy (detaching the tail for defense).
- Mammals display regeneration in the liver (compensatory hypertrophy) but external parts are not regenerated. Types include:
- Epimorphosis, Morphallaxis, Heteromorphosis, and Super-regeneration
Steps of Regeneration of a Limb in a Newt
- Wound healing: Migration of epidermal cells from wound edges.
- Blastema formation: Undifferentiated cells creating a bulge.
- Redifferentiation and morphogenesis: Developing rudiments (e.g. digits)
- Growth: Regenerating limb increasing to normal size.
Growth Factors
- Epidermal growth factor (EGF), Fibroblast growth factors (FGF), Platelets (Derived growth factors).
- These act locally to initiate cell mitosis, contributing to wound healing and limb regeneration
Polarity in Regeneration
- In organisms such as Hydra and planarians, bodies exhibit distinct polarity.
- Anterior end regenerates into head, while posterior end regenerates into the tail.
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