Stem Cell (5-7)

Cancer Stem Cells (CSCs)

• Stem cells are vital for regenerating and repairing organs like the heart, lungs, skin, germ cells, and other tissues.
• Cancer stem cells (CSCs) are responsible for cancer initiation, progression, metastasis, recurrence, and drug resistance.
• In 2020, approximately 19 million new cancer cases and 10 million deaths were reported.
• CSCs are a small subpopulation of tumor cells with self-renewal, dedifferentiation, tumorogenicity, and inherent chemo-and radiotherapy resistance.
• CSCs cause tumor relapse and failure of conventional therapies.
• CSCs originate from somatic stem cells, adult progenitor cells, and adult somatic cells.
• CSC features include self-renewal, diverse progeny, and immortality.
• Telomerase activity in CSCs is high, contributing to their immortality.
• The CSC hypothesis proposes that CSCs are quiescent (tumorigenic) and resistant to chemotherapy, leading to the formation of new tumors.
• Normal cells are small, uniformly shaped, have a relatively large volume, conform to cell size and shape, and cells within the tissue are arranged into discrete tissues.
• Normal cells are able to differentiate, have a normal presentation of cell surface markers, which have lower levels of dividing cells, and have clearly demarcated tissue compartments.
• Cancer cells are large, have variable shaped nuclei, and relatively small cytoplasmic volume.
• Cancer cells can vary in cell size and shape, with disorganised cells arrangements and a loss of normal specialized features.
• Cancer cells have elevated expression of certain cell markers. Large numbers of dividing cells and poorly defined tumor boundaries are further common characteristics of cancer cells than normal cells.
• Cancer is preceded by damaged DNA that alter cell processes including those that regulate growth and division.
• Free radicals in the body take electrons from structures which can lack an electron, causing oxidative stress.
• Free radicals can build up from radiation, chemicals, chronic malnutrition, excessive intake of calories, or extreme exercise.
• High amounts of oxidative stress are associated with high rates of cancer.
• Optimizing DNA repair enzymes, such as by using antioxidants, is important.
• Stem cells do not divide rapidly, therefore conventional chemotherapy targeting rapidly dividing cells does not target stem cells.

Exosomes

• Extracellular vesicles (EVs) are membrane-derived nano-meter-sized vesicles.
• Normal, diseased, and transformed cells release EVs in vitro and in vivo.
• Exosomes contain lipids, proteins, mRNAs, non-coding RNAs, and DNA.
• Exosomes can be generated intracellularly from multi-vesicular bodies (MVBs).
• Exosomes are produced by budding from the extracellular membrane.
• Apoptotic vesicles are released upon cell fragmentation.
• Exosomes can be used in diagnostics, immunotherapy, and combating diseases and pathological situations like senescent aging, cancer, and arthritis.
• Exosomes can act as a targeted drug delivery vehicle and potentially treat diseases, e.g. Alzheimer's disease and Parkinson's disease.
• Exosomes are small in size (~30-150 nm), have complex properties, and are stable during storage.
• Compared to stem cell therapies, exosomes do not present issues in tumor formation.

Stem Cell Banking

• A stem cell bank collects and stores human stem cells for various uses.
• Public and private banks exist, with donors needing similar HLA types for transplantation to avoid rejection.
• Donor selection considers completely matched siblings as the ideal match, with partially matched donors acceptable if no exact match is available.
• Race/ethnicity also play role in donor recruitment.
• Cryopreservation techniques, such as using freeze-drying and spray-drying, are implemented to preserve stem cells for long periods.

Tissue Engineering

• Tissue engineering utilizes interdisciplinary fields' principles in engineering, materials, and biochemistry to restore, maintain, or improve biological functions.
• The goal of regenerative medicine is to exploit these cells either by transplanting them from an exogenous source or by activating endogenous stem cells pharmacologically.
• Tissue engineering involves the use of scaffolds (biocompatible), in vitro culture, and tissue implantation to generate functional tissues and organs.
• Potential applications include creating artificial tissues (bladders), organs, and even entire body parts like hearts.
• Advantages of tissue engineering include eliminating transplant rejection, saving lives, improving lives, and potentially eliminating many surgeries for treating illnesses.
• Disadvantages are difficulties in designing scaffolds, necessary research and understanding of cadaver organs and tissues, cells need to stay alive inside body and continue to functioning and ethical concerns.