Stem Cells L16

• Stem cells are unspecialized cells with multipotent and pluripotent capabilities and long-term self-renewal.
• Differentiated cells are specialized, unipotent cells with very limited self-renewal.
• Unipotent cells give rise to only one cell type.
• Multipotent cells can give rise to many cell types.
• Pluripotent cells can give rise to all three lineages.

Symmetrical and Asymmetrical Cell Division

• Stem cells can make copies of themselves through symmetric cell division.
• Cells differentiate via asymmetrical cell division.

Molecular Characteristics of Embryonic Stem Cells

• Express pluripotency-associated transcription factors like Oct4, Nanog, and Sox2, which maintain self-renewal.
• Have lower DNA and histone methylation. More methylation leads to more silencing of gene expression.
• Exhibit high expression of telomerase.
• Injection of ESCs into an immune-compromised animal can lead to teratomas, tumors containing tissue from all three germ layers.

Limitations of ESCs

• Ethical and practical concerns exist.
• Destruction of blastocysts occurs due to the removal of the inner cell mass (ICM).
• There is a lack of diversity among ESC lines, as most are donated from IVF.

Induced Pluripotency

• Adult stem cells are undifferentiated cells found among differentiated cells in fully formed organs.
• Adult stem cells can renew themselves or differentiate into specialized cell types of the tissue or organ where they reside.
• The stem cell niche is the microenvironment around stem cells that provides support and signals regulating self-renewal and differentiation.
• The primary role of adult stem cells is to maintain and repair the tissue in which they are found.
• Adult stem cells are capable of asymmetrical cell division.
• They are usually multipotent and restricted to within one germ line.
• Adult stem cells are a rare population of cells in the body.
• The origin of adult stem cells is unknown.

Hematopoietic Stem Cells

• HSCs can be harvested from bone marrow, peripheral blood, and cord blood.
• The niche for HSCs is the bone marrow.
• They are the most clinically used type of stem cell to treat blood cancer, bone marrow disorders, genetic blood diseases, and recently, multiple sclerosis.

Mesenchymal Stromal Cells

• MSCs are defined as non-hematopoietic multipotent mesenchymal cells from connective tissue/blood vessels.
• MSCs are multifunctional, with immunomodulation and "progenitor" functions.
• They are the most used "stem cell" in research due to their multifunctional nature.
• MSCs are easy to isolate from various vascular tissues, most commonly bone marrow and umbilical cord blood.
• They are easy to propagate in vitro.
• MSCs are highly amenable to a variety of applications, including transplantation, tissue engineering, and genetic modification.
• There is extensive evidence that MSCs can differentiate into mesoderm-derived cell types, especially bone, cartilage, and fat in vitro, which is useful for tissue engineering.

Mesenchymal Stromal Cells: Transplantation

• The unique immunomodulation properties of MSCs have the potential to speed up healing.
• MSCs act as "conductors" of the immune response to attenuate inflammation.
• Immunomodulation does not rely on differentiation properties of cells.
• MSCs can become tissue in vitro and down-regulate cells, helping to calm inflammation.

Summary of Stem Cells

• ESCs and iPSCs are pluripotent stem cells capable of differentiating into all cell types of the embryo.
• iPSCs have the added advantage of being derived from differentiated adult cells, and can therefore be used for disease modeling or patient-specific cell-based treatments.
• Adult stem cells, found in adult organisms, are responsible for organ/tissue repair and regeneration.
• HSCs are used clinically to replenish blood-derived cells in blood disease/cancers.
• MSCs are used for either cell-based tissue engineering strategies or can be transplanted to assist with immunomodulation.