Stem Cells: Characteristics and Overview

Stem Cells: An Overview

• Stem cells are undifferentiated cells with the potential to form specialized cells.
• Stem cells are the first cells to form when a fertilized egg begins to divide.
• These cells can divide continuously and have the ability to differentiate into various cell types, including liver, brain, cartilage, and skin.
• Stem cells are 'blank' or unspecialized.
• Proliferation and renewal is the process of cells dividing and renewing for long periods.
• Stem cells can give rise to specialized cell types through differentiation.

Stem Cell Characteristics

• Express the transcription factor Oct-4.
• Can be induced to continue proliferating or differentiate.
• Lack the G1 checkpoint in the cell cycle.
• Spend most of the time in the S phase of the cell cycle, during which they synthesize DNA.
• ES cells do not require any external stimulus to initiate DNA replication, unlike differentiated somatic cells.
• Do not show X inactivation; X inactivation doesn't occur in undifferentiated ES cells.
• In every somatic cell of a female mammal, one of the two X chromosomes becomes permanently inactivated.

Stem Cells and Adult Tissues

• They divide to produce one daughter cell which remains a stem cell, and one that divides and differentiates.
• Hematopoietic stem cells (blood-forming) were the first stem cells to be identified.
• Erythrocytes, granulocytes, macrophages, platelets, and lymphocytes are blood cells with specialized functions that are derived from the same population of stem cells.
• Most adult tissues have stem cells residing in distinct microenvironments or niches.
• Niches provide environmental signals to maintain stem cells throughout life and control the balance between self-renewal and differentiation.

Types of Stem Cells

• Embryonic stem cells compose the early human embryo.
• Totipotent stem cells can differentiate into any cell type.
• Early stages of embryo development are called totipotent.
• An embryo enters the blastocyst stage about 4 days after fertilization.
• Pluripotent stem cells can make almost any cell type and are found in the inner cell mass of a developing embryo.

Kinds of Stem Cells Defined

• Totipotent Stem Cells: Each cell can develop into a new individual; examples include cells from early (1-4 days) embryos.
• Pluripotent Stem Cells: Cells can form any (over 200) cell types; examples include some cells of the blastocyst (5 to 14 days).
• Multipotent Stem Cells: Cells are differentiated but can form a number of other tissues; examples include fetal tissue, cord blood, and adult stem cells.

Clinical Note - Embryonic Stem Cells

• Embryonic Stem Cells are mainly derived from In Vitro Fertilization (IVF).
• Pluripotent Stem Cells possess more potential to become any type of cell.

Adult Stem Cells

• Adult stem cells are undifferentiated cells in tissues, occurring in small numbers.
• Multipotent adult stem cells can develop into two or more different cell lines, but not any type of cells.
• Bone marrow stem cells are multipotent and can develop into several blood cell types.
• Unipotent stem cells can develop into only one cell line.

Induced Pluripotent Stem Cells (iPS Cells)

• iPS cells can differentiate into many cell types, are vastly renewable, easily accessible, and individual-specific.
• iPS Generation: Cells from patient can be isolated, treated with reprogramming factors and pluripotency can thereby be induced.

Stem Cell Location

• Stem cells can be found in bone marrow, skin, fat tissue, teeth, mammary tissue, and many other tissues.

Bone Marrow and Stem Cells

• Bone marrow is found in spongy bone and is where blood cells form.
• Bone marrow stem cells are used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
• Bone marrow stem cells can treat patients diagnosed with leukemia, aplastic anemia, and lymphomas, but need greater histological immunocompatibility.

Stem Cell Separation

• Stem cells are separated via fluorescent activated cell sorting.
• Cells in suspension are tagged with fluorescent markers specific for undifferentiated stem cells.
• Labeled cells are sent under pressure through a small nozzle and pass through an electric field.
• A cell generates a negative charge if it fluoresces and a positive charge if it does not.

Tissue Dynamics

• Hyperplasia is tissue growth through cell multiplication.
• Hypertrophy is the enlargement of pre-existing cells, such as muscle growth through exercise.
• Neoplasia is the growth of a tumor (benign or malignant) through the growth of abnormal tissue.

Tissue Repair Mechanisms

• Regeneration involves the replacement of damaged cells with original cells (e.g., skin injuries and liver regenerate).
• Fibrosis involves the replacement of damaged cells with scar tissue, where function is not restored.
• Keloid formation is healing with excessive fibrosis, resulting in raised shiny scars.

Tissue Engineering

• Production of tissues and organs in the lab can be achieved via tissue engineering.
• This involves a framework of collagen or biodegradable polyester fibers.
• These frameworks are seeded with human cells and grown in a "bioreactor" (inside of a mouse), which supplies nutrients and oxygen to the growing tissue.
• Skin grafts are already available, research is in progress on heart valves, coronary arteries, bone, liver, and tendons.

Therapeutic Cloning

• Therapeutic cloning involves the usage of unfertilized eggs, removal of egg chromosomes, the transfer of nucleus to enucleated egg, culture to early embryo and finally embryonic stem cells are cultured and differentiated to desired cell types.

Potential Uses for stem cells

• Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues for diseases, conditions, and disabilities.
• Parkinson’s disease, spinal cord injury, burns, heart disease, arthritis, and diabetes may be treated via pluripotent stem cells.
• Adult stem cells are currently used for leukemia treatments.
• Scientists expect to use embryonic stem cells to grow organs, such as liver and heart, to replace damaged ones.
• Leukemia patients treated with stem cells emerge free of disease, and injections can reduce pancreatic cancers.
• Adult stem cells may help jumpstart repair of eroded cartilage for rheumatoid arthritis.
• Embryonic stem cells might be trained to become pancreatic islets cells needed to secrete insulin for type I diabetes.

Potential Issues

• Potential Problems with Adult Stem Cells include Source of cell lines, Delivery of cells, Prevention of rejection of cells and suppressing tumors.
• Mutations in adult stem cells can lead to leukemia.

Stem Cell Controversies

• Embryonic stem cells are derived from extra blastocysts that would be discarded following IVF.
• Extracting stem cells destroys the developing blastocyst (embryo).
• Questions for consideration include whether an embryo is a person, is it morally acceptable to use embryos for research, and when do we become "human beings?"