Understanding Adult Stem Cells

Stem Cell Biology - Course Information

• Course name: Stem Cell Biology
• Course code: Cell Biology MED105
• Professor: A. Stephanou
• Institution: European University Cyprus, School of Medicine

Stem Cells and their use in Therapy

• Course: MED102
• Institution: European University Cyprus (EUC)
• Presented by: Dr. A. Stephanou

Objectives

• Understand different types of stem cells and their characteristics
• Explore how stem cells are derived
• Analyze problems associated with stem cell therapy
• Examine stem cells in treating cardiac, hematopoietic, and diabetic diseases

Stem Cell History

• 1998: Researchers extracted stem cells from human embryos for the first time.
• 1999: First successful human transplant of insulin-producing cells.
• 2002: The Juvenile Diabetes Research Foundation International created a $20 million fund to support stem cell research.
• 2004: Harvard researchers grew stem cells from embryos using private funding.
• 2012: Stem cell scientists Sir John Gurdon (UK) and Shinya Yamanaka (Japan) shared the Nobel Prize for their work in medicine.

Stem Cell - Definition

• A cell capable of continuous division and differentiation (development) into various cell types and tissues.

Stem Cell Characteristics

• "Blank cells" (unspecialized)
• Capable of self-renewal (proliferation and renewal) for extended periods
• Potential to develop into specialized cell types (differentiation)

Kinds of Stem Cells

• Totipotent: Each cell can develop into a completely new individual. Example: cells from early (1-3 day) embryos.
• Pluripotent: Cells can form any of the 200+ types of cells in the body. Examples: Some cells of the blastocyst (5 to 14 days old).
• Multipotent: Cells are differentiated but can still form a limited number of other tissue types. Examples: Fetal tissue, cord blood, adult stem cells.

Types of Stem Cells (Diagram)

• Totipotent, Pluripotent, and Multipotent stem cells are depicted in a diagram showing their different abilities and further differentiation

Kinds of Stem Cells (Further Information)

• Embryonic Stem Cells: Derived from a five to six-day-old embryo.
• Embryonic Germ Cells: Derived from the part of a human embryo or fetus.
• Adult Stem Cells: Undifferentiated cells found among specialized or differentiated cells in a tissue or organ after birth. Examples: Skin, fat cells, bone marrow, brain, and many other organs and tissues.

Multipotent Stem Cells

• Limited in the types of cells they can become. Examples: specific types of blood cells, brain cells, heart cells, bone cells.

Blastocyst

• A blastocyst is a type of early embryo containing a pluripotent stem cell

Bone Marrow

• Found in spongy bone where blood cells are formed.
• Used to replace damaged bone marrow with healthy bone marrow stem cells.
• Can treat conditions like leukemia, aplastic anemia, and lymphomas.

Blood Cell Formation

• Hemangioblasts are multipotent precursor cells that can differentiate into blood cells.
• A diagram is shown that demonstrates the different steps of blood cell development as it forms multiple blood types.

Hemangioblasts (Diagram & Description)

• A diagram illustrates the overall scheme for hematopoiesis, showing how embryonic stem cells lead to angioblasts that form blood vessels and universal blood stem cells, generating myeloid and lymphoid precursors.

Precursor Stem Cells for Muscle

• Mesoangioblasts and Satellite cells are precursors for muscle cells.
• Key point: Satellite cells support muscle regeneration.

Genetic Control of Muscle Cell Differentiation

• MyoD is a master regulator of muscle cell differentiation from myogenic precursor cells.
• Myogenin, Myf-5, and MRF-4 are transcription factors activating genes needed for differentiation.
• Diagram showing the basic regions, and helix-loop-helix structures

Stem Cell Applications

• Tissue repair (nerve, heart, muscle, organ, skin)
• Cancers
• Autoimmune diseases (diabetes, rheumatoid arthritis, MS)

Medical Importance of Stem Cells

• Stem cells can potentially replace damaged or diseased tissues.
• Potential applications for treating Alzheimer's, Parkinson's, stroke damage, diabetes, and arthritis.
• Cloning a patient’s cell to create a blastocyst and induce stem cells to create cardiac muscle could treat heart conditions.
• Current limitations in US government funding and political issues impede progress in embryonic stem cell research.

Creating iPS Cells (Diagram)

• A step-by-step diagram illustrates the process of creating induced pluripotent stem (iPS) cells from adult cells such as skin or fibroblasts. iPS cells can then be differentiated into different cell types.

Challenges to Stem Cell/Cloning Research

• Controlling stem cell development and proliferation after transplantation
• High possibility of rejection due to stem cells being foreign tissue
• Risk of contamination by microorganisms (viruses, bacteria, fungi, Mycoplasma)

Technical Challenges

• Cell lines might have mutations (errors in the genetic code)
• Delivery to target areas: Getting stem cells to the right place.
• Prevention of rejection of transplanted cells by the immune system.
• Suppressing tumor formation.

Problems with Adult Stem Cells

• Mutations in stem cells can lead to leukemia.
• A diagram illustrates how mutations in stem cells can result in the formation of leukemia cells.

Why is Stem Cell Research Important?

• Stem cells can replace damaged cells in many body parts.
• Stem cells allow for the study of development and genetics.
• Stem cells can test drugs and chemicals in a controlled environment.

Mechanism of Cardiac Diseases and Cardiac Stem Cell Therapy

• Describes tissue regeneration in animals as an example of potential stem cell healing therapy for damaged parts.

Cardiac Regeneration

• Cardiomyocytes initiate DNA synthesis and re-enter the cell cycle, sometimes.
• Dedifferentiation of cardiomyocytes near damage occurs before loss of contractile proteins.
• Undifferentiated stem or progenitor cells dominate the process.
• In mammals, cardiomyocytes rarely divide post-injury.
• Diagrams show examples in different biological organisms.

Stem Cells Used for Cardiac Repair

• Describes the potential and challenges of using stem cells to repair hearts by highlighting the limitations of cardiomyocyte proliferation, terminal differentiation, proliferation capacity, and inadequate chemotaxis.

• Cardiac regeneration may be limited by the hostile microenvironment affecting stem cell regeneration.

• Inadequate mobilization, insufficient homing, and poor multipotency can occur during bone marrow stem cell mobilization.

• Loss of viable stem cells and stem cell function due to age is a significant barrier.

Cardiac Tissue Engineering

• Adult hearts, like brains, are predominantly made up of differentiated cells that may have stem cells supporting regeneration.
• Discovery of Yaakov Nahmias created the first heart model grown from stem cells including all of the key structures of a heart--ventricles, atria, epicardium, endocardium, and an artificial pacemaker.

Clinical Trials of Hematopoietic Cell Transplantation

• A complex diagram illustrating the processes and cells involved in hematopoietic stem cell transplantations. Different types of cells like hematopoietic stem cells, NK cells, T progenitors, B progenitors, Dendritic Cells, and various blood cells.

Stem Cells and Diabetes

• Beta cells are not generated from adult pancreas stem cells.
• Adult stem cells are unlikely to cure diabetes.
• Embryonic stem cells have been shown to produce insulin-producing beta cells.

Germ Layer Differentiation

• Diagram illustrates how the three germ layers (ectoderm, mesoderm, and endoderm) give rise to the various organ systems.

Forming Specialized Cells

• Growth factors and other signals direct stem cell differentiation and dictate the cell type.
• The same factors can guide the differentiation of human embryonic stem cells in culture for different cell types.

Identifying Signals for Differentiation

• Early endoderm cells receive cues (signals) that control their differentiation into various cells.
• Signals include transcription factors, cytoplasmic factors, and growth factors.
• Cells physically contact each other/adjacent blood vessels to communicate for proper differentiation signaling.

The Future Task

• Directing cultured embryonic stem cells to become insulin-producing beta cells.

Cancer Stem Cells

• Rare cells within organs with self-renewal capacity and differentiation potential crucial for organogenesis.
• Rare cells within tumors with self-renewal capacity and differentiation potential critical to tumor growth.

Cancer Stem Cell Therapy

• Cancer stem cells have been identified in a range of cancers (breast, prostate, skin, blood, brain).
• Cancer stem cells exhibit persistent self-renewal and differentiation potential within the tumor.
• Recent evidence suggests specific genes are abnormally expressed in cancer stem cells.
• The aim of cancer stem cell therapy is to kill, stop the proliferation, or differentiate these cells to stop cancerous growth.

Therapeutic Implications of Cancer Stem Cells

• Cancer therapy needs to consider the different sensitivities of cancer stem cells and non-tumorigenic cells.
• Most therapies primarily target rapidly growing cells rather than the quiescent, or dormant, cancer stem cells.

Summary of Stem Cell Source

• A flow chart summarizes how different stem cell sources lead to different specific cells, and their potential medical use.

Summary of Stem Cell Source (Isolation, Delivery, Survival, and Electro-mechanics)

• Diagram illustrates isolation and delivery methods for different types of stem cells.
• Survival and proliferation of stem cells in the host body are critical.
• Electro-mechanical integration of stem cells with the host tissue is also important for long-term effects.
• Diagram also demonstrates the challenges involved in these different stages of stem cell therapy.