Stem Cells: Types and Uses

Stem Cells

• Stem cells are undifferentiated, unspecialized cells.
• Stem cells possess self-renewal capabilities
• They can be maintained in an undifferentiated state.
• They possess the capacity to differentiate into specialized cell types.
• Examples of specialized cell types include muscle cells, red blood cells, nerve cells, or brain cells.
• There are two broad types of mammalian stem cells
  • Embryonic stem cells that can be isolated from the inner cell mass of blastocysts.
  • Adult stem cells that are found in adult tissues such as skin, muscles, umbilical cord blood, brain, heart, and bone marrow.
• Stem cell therapy will dramatically change the treatment of human diseases.
• Human stem cells could be used in the generation of cells and tissues for cell-based therapies.
• This involves treating patients by transplanting specialized cells that have been grown from stem cells in the laboratory through stem cell culture.
• Stem cells are used for:
  • Leukemia treatment, where bone marrow transplants replace abnormal stem cells to produce normal blood cells.
  • Cardiovascular disease treatment, by repairing damaged heart cells post-heart attack.
  • Type 1 diabetes mellitus treatment, replacing damaged pancreatic beta cells with functional ones to secrete insulin.
  • Spinal cord injuries treatment, to regrow damaged neurons.
  • Alzheimer's disease treatment, to replace damaged brain cells.
  • Muscle damage repair.

Antigen-Presenting Cells (APCs)

• APCs include Dendritic cells, Macrophages, and B lymphocytes.
• These occur in the epithelium of the skin, gastrointestinal tract, and respiratory tract.
• These locations are common entry points for microbes.
• APCs capture and transport antigens to the peripheral lymphoid tissues.
• APCs also process antigens.
• Present peptides derived from antigens to T lymphocytes.
• They are rich in class II MHC molecules.

Class II MHC pathway of antigen processing and presentation

• Protein antigens are taken from the extracellular environment.
• Proteins are degraded by lysosomal proteases.
• Resulting peptides are presented to CD4+ cells with class II MHC molecules.

Class I MHC pathway

• Cytosolic proteins, e.g., from intracellular microbes.
• Proteins are degraded by a structure called the proteasome.
• Resulting peptides are presented to CD8+ cells with class I MHC molecules.

Phagocytes

• Definition: Cells that can recognize, ingest & kill microbes & foreign bodies.

Types of phagocytes

• Monocytes: These are large mononuclear cells circulating in the blood.
• They ingest microbes in the blood.
• Macrophages: These are the tissue residents of monocytes and ingest microbes in the tissues.
• Neutrophils are also called polymorphonuclear leukocytes (PMNs).
• They are the most numerous leukocytes in the blood.
• Neutrophils are very effective at killing bacteria.
• An increase in neutrophil count in the blood indicates acute infection.
• Neutrophils ingest microbes in the circulation, enter tissues at the site of infection, and die after a few hours.

Stages of phagocytosis

• Delivery of phagocytic cell to the site of infection.
• Diapedesis: Histamine stimulates phagocytes to migrate through the blood vessel wall into tissue.
• Chemotaxis: Chemotactic factors, like chemokines & complement components (C3a, C4a, & C5a), attract phagocytes towards microbes in tissue.
• Recognition of microbes.
• Phagocytes recognize and bind microbes through receptors on their outer surface, e.g., mannose receptor & Toll-Like receptor.
• Adherence to target (opsonization).
• The microbe is coated with IgG or complement (C3b).
• IgG or C3b bind with their receptors on phagocytic cells.
• This brings the microbe near the phagocytic cell, easing phagocytosis.
• Opsonins are antibodies (IgG) or C3b capable of enhancing phagocytosis.
• Ingestion of target.
• The cell membrane of phagocytes invaginates to enclose the microbe.
• The microbe becomes enclosed in the cytoplasm surrounded by a cell membrane and forming a vacuole called a phagosome.
• Phagolysosome formation
• The phagosome fuses with a lysosome, forming a phagolysosome.
• Intracellular killing.
• Oxygen-dependent (Respiratory bursts): O2 free radicals like H2O2, O2 & OH, and toxic nitrogen oxide are used.
• Oxygen-independent agents: Lysosomal granules with basic proteins damage the permeability barrier in bacteria, fungi, & viruses; Lactoferrin chelates iron to inhibit bacterial growth; Lysosomal enzymes like lysozyme & nuclease are present; Low pH due to lactic acid prevents growth.
• Digestion.
• Neutrophils: Short-lived and lyse after phagocytosis; dead and dying neutrophils are a major component of pus.
• Macrophages: Egest digested debris and digest microbes into small antigen peptides presented on MHC to T helper cells.

Case scenario

• A 2-month-old girl, born at a gestational age of 38+2 weeks, was referred to the hospital for investigations regarding persistent pneumonia.
• She suffered from recurrent infections such as neonatal sepsis and gastroenteritis since the 6th day of her life.
• She received three recent courses of antibiotics (cefepime, clindamycin, and imipenem) due to persistent pneumonia.
• The neutrophil respiratory burst activity test was markedly decreased.

Additional points

• Movement of cells in response to a chemical stimulus is called chemotaxis.
• Opsonins include C3b.
• Toxic nitrogen oxide is involved in intracellular killing by oxygen-dependent activity.