topic 8

BIO152 Cell Biology: Stem Cells, Differentiation and Cancer

Learning Objectives

  • Understand the role of stem cells in normal development.

  • Compare the characteristics of stem and differentiated cells.

  • Compare characteristics of healthy stem and differentiated cells with cancer cells.

  • Understand changes to cells that make them cancerous.

Growth and Cell Turnover

  • Development starts from a single cell, leading to a multicellular organism (approximately 10^13 cells).

  • Continuous wear and tear requires cellular repair and turnover.

  • Approximately 330 billion cells are turned over daily:

    • 86% are blood cells

    • 12% are gut cells

  • Cell growth, replacement, and death are highly regulated through programs of cell division and differentiation.

Stem Cells

  • Originates from the zygote, leading to ~220 different specialized cell types; all cells maintain identical DNA.

  • Stem cells differentiate into mature cells.

Definitions and Characteristics

  • Stem Cells:

    • Defined by two unique characteristics:

      1. Unspecialized

      2. Self-renewing

  • They undergo mitotic division where daughter cells can remain unspecialized or differentiate based on conditions.

  • Hayflick limit: non-stem cells cannot continuously reproduce.

  • Resident stem cells are crucial for tissue homeostasis.

Differentiation of Stem Cells

  • All cells have the same DNA, but specific conditions lead to differentiation.

  • Factors influencing differentiation:

    • External signals:

      • Chemical signals from other cells

      • Physical contact with adjacent cells

      • Environmental molecules

    • Internal signals:

      • Changes in gene expression trigger differentiation.

Stem Cell Potency Levels

Potency Defined

  • Stem cell potency: The ability to differentiate into various cell types.

Hierarchy of Potency Levels

  1. Totipotent:

    • Can generate an entire organism (e.g., fertilized egg).

  2. Pluripotent:

    • Can differentiate into any of the three germ layers; cannot form a complete organism.

  3. Multipotent:

    • Limited differentiation potential (e.g., tissue stem cells).

  4. Unipotent:

    • Gives rise to a single cell type (e.g., muscle stem cells).

Further Differentiation

  • Progenitor cells derive from stem cells.

  • They have limited self-renewal capacity and can differentiate into multiple cell types.

  • Final Cell Types:

    • Terminally differentiated

    • Fully mature cells that do not divide.

Stem Cells in Medicine

  • Embryonic stem cells can be cultured and retain multi-lineage potential.

  • Current applications include:

    • Bone marrow transplants (leukemia treatment)

    • Skin grafts

  • Future possibilities: Organ regeneration from patient's own cells (autologous transplant).

Induced Pluripotent Stem Cells (iPSCs)

  • Adult somatic cells can be genetically reprogrammed to become pluripotent; significant for drug development and transplantation.

Stem Cells in Research

  • Potential medical uses:

    • Stroke

    • Traumatic brain injury

    • Alzheimer’s, diabetes, etc.

Cancer Overview

  • Cancer is an uncontrollable growth of abnormal cells, classified into several diseases.

  • It leads to invasive behavior and metastasis, threatening local tissues and overall health.

Cancer Statistics

  • Approximately 134,000 new cancer cases annually in Australia affecting:

    • Prostate

    • Breast

    • Colorectal

    • Lung cancers.

Healthy vs. Cancer Cells

  • Balance between cell death (differentiation) and cell renewal maintains health; exceeding apoptosis leads to tumor growth.

  • Carcinogenesis: A process where normal cells are converted to precancerous, leading to uncontrolled growth.

Types of Cancer

  • Carcinoma:

    • Comprises 90% of all cancers, affecting epithelial cells.

  • Sarcomas:

    • Affect supporting tissues (e.g., bone, muscle).

  • Lymphoma/Leukemia:

    • Affect blood and lymphatic tissues.

Causes of Cancer

  • Oncogenes: Genes that promote cell division; mutations can lead to cancer.

    • Examples include: BCR-ABL kinase, MYC, KRAS.

  • Activation can occur through duplication, mutation, or loss of anti-oncogenes.

Carcinogenesis Process

  1. Initiation:

    • Changes normal cells to precancerous state.

  2. Promotion:

    • Repeated exposure to agents stimulates cell growth.

  3. Tumor Progression:

    • Loss of normal growth controls leading to tumor formation.

Cancer Hallmarks

  • Cancer cells exhibit glycolytic behavior (Warburg effect) to meet energy demands, favoring glucose uptake.

Benign vs. Malignant Tumors

  • Benign:

    • Localized, generally non-dangerous (e.g., warts).

  • Malignant:

    • Invasive and may metastasize, altering normal tissue function.

Invasion and Metastasis

  • Invasion:

    • Direct migration of cancer cells into neighboring tissues.

  • Metastasis:

    • Transport of cancer cells to distant sites through blood or lymphatics.

Multi-Hit Theory of Cancer

  • Progression of cancer requires multiple genomic changes promoting proliferation and metastasis.

Review Questions

  1. Compare characteristics of healthy stem cells and cancer cells.

  2. Examine stem cell potency levels and differentiation stages.

Textbook Readings

  • Becker's World of the Cell (9th Ed.) - Chapter 26 on Cancer Cells.