Stem Cell Therapies Flashcards
What are stem cells?
undifferentiated cells that are capable of self-renewal and have the potential to differentiate into various cell types
→ They are the earliest cells of cell lineage in all tissues and are found in embryonic and adult organisms
Embryonic stem cells
are more potent than adult stem cells as they are capable of differentiating into various cell types
→ Pluripotent!
Adult stem cells
less potent, and more restricted as they can only differentiate into specific lineages
→ Multipotent
Where do stem cells come from?
Amniotic fluid - both the amniotic membrane and amniotic fluid are good sources of embryonic stem cells
Human umbilical cord - cord blood can be collected from the cord which consists of hematopoietic and mesenchymal stem cells → hematopoietic stem cells can from RBCs and cells of the immune system, while the mesenchymal cells can generate bone, cartilage and other types of tissue
Bone marrow - mesenchymal stem cells were first found in bone marrow, and it is the most frequently used source of mesenchymal cells. Subsequently hematopoietic stem cells are also found in bone marrow, making it an attractive candidate for regenerative medicine and therapeutic purposes
Adipose tissue - adipose tissue-derived stem cells are mesenchymal cells that have the potential for self-renewal and multipotency. They can differentiate into adipocytes, chondrocytes, myocytes ,osteoblasts and neurocytes
First Generation Stem Cells
Hemopoietic Stem cells & Mesenchymal Stem cells
What can Haematopoietic stem cells (HSCs) develop into?
All types of blood cells, including WBCs, RBCs and platelets
They are the most commonly used stem cell type
Mesenchymal stem cells are found in…
Muscles, Liver and bone marrow
Can be isolated more easily, can produce a higher yield but the procedure is more painful
Clinical trials often fail to improve primary end points
Second Generation Stem Cells
Embryonic stem cells & induced pluripotent cells
Embryonic stem cells (hESC)
→ found in the inner cell mass of the blastocyst post 5 days of development
These cells are potentially immortal & derived from embryos before implantation
Pluripotent
Used in treatment of AMD → pluripotent derived retinal pigment epithelium
Oligodendrocytes for spinal cord injuries
?? Ethical concerns, as it involves the destruction of human embryos
Induced plutipotetn cells (iPSC)
→ formed when the adult cells are cultured with embryonic stem cells where a fusion occurs between these cells to produce new cells with stem cell-like properties - i.e., they are reprogrammed
Similar to hESC as they can also be stimulated to differentiate into different cell types
Challenges remain as chromosomal abnormalities may appear due to reprogramming process
What are next generation stem cells?
Both 1st and 2nd generation stem cells are being transformed though various engineering strategies to improve their specificity, efficacy and expand their use in therapeutic areas
2 uses of next generation stem cells
- Use as a delivery vehicle for therapeutics
- Use as enhanced therapeutic agents themselves
Tools to create Next Generation stem cells?
Virus mediated trandsuction
Gene editing tools e.g., CRISPR-Cas
Chemogenetics
Optogenetics
Copper-free click chemistry
What is Virus mediated transduction?
Transduction of HSCs with exogenous genes which can be used to:
- Drive expression of proteins not normally expressed in stem cells - prodrug converting enzymes
- Chimeric antigen receptors - haemato-oncology
Optogenetic actuators - to control cell signalling pathways
- Increase expression of proteins normally expressed in stem cells - GFs, trophic factors
- Express WT proteins as a mechanism to functionally compensate for genetic mutations
What is Kymriah?
→ an immuno cellular therapy containing tisagenlecleucel, autologous T cells genetically modified ex vivo using a lentivirus vector encoding anti-CD19 chimeric antigen receptor (CAR)
Intended for autologous use only, manufacturing and release of the drug usually takes about 3-4 weeks
