Stem Cells and Tissue Renewal

Stem Cells and Tissue Renewal

The Multicellular Habitat

  • Cells of Multicellular Organisms:
    • Highly specialized, with over 200 different types in the human body.
    • Arranged into tissues, organs, and organ systems.
    • Cells are unable to survive outside the body’s habitat.

Specialized Cell Types

  • Early Embryo:
    • Cells are initially identical.
  • Differentiation:
    • The process that results in specialized cell types.
    • Some differentiated cells continue to divide, while many others become "terminally differentiated."
    • Tissue Stem Cells:
    • These supply replacement cells, particularly in tissues where differentiated cells do not divide or do so infrequently.

What is a Stem Cell?

  • Characteristics of Stem Cells:
    • Not terminally differentiated.
    • Retain the capacity to divide indefinitely.
    • Upon division, daughter cells can:
    • Remain as stem cells
    • Commit to terminal differentiation
    • Possibly pass through intermediate cell types.
    • Stem Cell Systems:
    • Refers to tissues that depend on stem cells for renewal.

Stem Cell Division

  • Environmental Asymmetry:
    • Involves two daughter cells produced during division, with some remaining as stem and others differentiating.
    • The ratio of stem cells to differentiated cells is influenced by environmental factors.
  • Divisional Asymmetry:
    • Each stem cell division consistently results in one stem cell and one cell destined for differentiation.

Stem Cell Division Strategies

  • Types:
    • Environmental Asymmetry
    • Divisional Asymmetry
  • Leaves behind terminally differentiated cells as a result of division.

Stem Cell Tissue Systems

  • Examples:
    • The skin system.
    • The blood system.

Epidermis

  • Definition:
    • The fundamental component of skin.
  • Derived Structures from Epidermis:
    • Fingernails
    • Hair
    • Horns, antlers, and feathers
    • Skin glands.

Interfollicular Epidermis

  • Composition:
    • Comprised of multiple layers of cells called keratinocytes.
    • Keratinocytes differ across various layers, which contribute to skin function.

Keratinocyte Types

  • Basal Cells:
    • Attached to the basal lamina, which in turn is attached to the extracellular matrix.
  • Prickle Cells:
    • Named for visible desmosomes.
  • Granular Cells:
    • Final layer of living cells.
  • Keratinized Squames:
    • Terminally differentiated epidermal cells.
  • Shedding Squames:
    • Dead keratinized cells that are excreted from the skin surface.

Basal Cells

  • Function:
    • The dividing cells of the epidermis.
  • Fate of New Basal Cells:
    • New basal cells either:
    • Add to the population of basal cells.
    • Begin differentiation into other epidermal cell types, transitioning from basal to shed squames.
  • Keratinized Squame:
    • Is a terminally differentiated epidermal cell.
  • Significance of Basal Cells:
    • They serve as skin tissue stem cells.

Transit Amplification

  • Process:
    • The first cells generated from stem cell division typically undergo several rounds of additional division prior to further differentiation.
    • Transit Amplifying Cells:
    • These cells reflect the mechanism that produces a higher number of differentiated cells from a relatively smaller population of stem cells.

Immortal DNA Strand Hypothesis

  • Normal Segregation of Chromosomes:
    • During DNA replication, identical sister chromatids are separated, and their distribution among daughter cells occurs randomly.
  • Asymmetrical Segregation Hypothesis:
    • One of the template strands may have a "tag," leading to its segregation along with the other tagged strands to a single daughter cell.
    • This establishes which daughter cell will retain stem cell identity.

Hematopoietic Stem Cells

  • Function:
    • Responsible for blood cell production and differentiation, known as hemopoiesis.
  • Location:
    • Reside in bone marrow.

Commitment of Progenitors

  • Types of Progenitor Cells:
    • Multipotent Hematopoietic Stem Cell:
    • Can commit to various cell lineages (T cells, NK cells, B cells).
    • Common Lymphoid Progenitor:
    • Gives rise to specific immune cells.
    • Common Myeloid Progenitor:
    • Engages in the pathway to red blood cells, macrophages, neutrophils, etc.

Adult Stem Cells

  • Characteristics:
    • Tissue-specific and stem cells from one tissue can exhibit changes when grown in the presence of different tissue cells.
    • They may lose their stem cell properties and acquire characteristics that differ from their origin.
  • Stem Cell Plasticity:
    • Describes the phenomenon of stem cells adapting and functioning outside their normal pattern.

Stem Cell Treatments

  • Hematopoietic Stem Cell Treatments:
    • Used to replace unhealthy blood cells, especially in conditions like leukemia.
    • Treatment may involve irradiation or chemical destruction of blood cells, followed by transfusion or bone marrow transplant to replace the cells.

Genetically Engineered Hematopoietic Stem Cells

  • Process:
    • Removal of cells, followed by culturing and genetic modification.
  • Modifications:
    • Produce a significant gene product for patients lacking that ability.
    • Mimic disease conditions for research and therapy testing.

Other Stem Cell Treatments

  • Epidermal Stem Cells:
    • Cultured healthy skin cells are used to replenish areas of skin damage, such as in burn victims.
  • Neural Stem Cells:
    • Still experimental in non-human subjects with potential implications but complex differentiation processes to navigate.

Embryonic Stem Cells

  • Definition:
    • Referred to as pluripotent stem cells; capable of differentiating into any cell type.
  • Source:
    • Derived from cells at the blastocyst stage, they can be cultured indefinitely.
    • When transplanted into a new blastocyst at the same time point, they differentiate normally.

Pluripotent Stem Cells

  • Challenges:
    • If placed back into a different time point, they may result in tumor formation.
    • This is correlated with the lack of proper extracellular signals which guide differentiation.

Pluripotent Stem Cell Potential

  • Current Research:
    • Human pluripotent stem cells are now collected and grown in culture, with the potential to:
    • Generate cells for tissue regeneration (muscle tissue for muscular dystrophy, nerve tissue for Parkinson's disease, heart tissue).
    • Replace defective cells critical for important compound production (e.g., insulin-secreting pancreatic cells).
    • Mechanisms of control during this process are complex and under active study.

Exam Information

  • Exam 4
    • Date: Thursday, December 4
    • Time: 8:00 am – 9:15 am
    • Location: DW 103
    • Format: Scantron, not cumulative.