Stem cells

• features of stem cells:

  • undifferentiated, unspecialised, have no tissue-specific structure, cannot perform tissue-specific function
  • can undergo extensive proliferation and are capable of self-renewal via mitosis, maintains constant pool of stem cells
  • can differentiate into specialised cells upon recieving appropriate molecular signals (such as by transcription factors, growth factors and hormones), to replace dead cell
• totipotent stem cell:

  • can differentiate into all cell types that make up an entire organism, including extra-embryonic tissue such as the placenta
  • eg zygotic stem cell
• pluripotent stem cell:

  • can differentiate into all cell types that make up an organism except for extraembryonic tissues such as placenta
  • eg embryonic stem cell
• multipotent stem cell:

  • can differentiate into several related specialised stem cells, but far fewer types than the pluripotent embryonic stem cell
  • eg lymphoid stem cell, myeloid stem cell
• Mitosis (symmetric division)

  • produces 2 daughter stem cells with same developmental and differentiation potential as parent cell
  • maintains a large pool of stem cells for further differentiation
• Mitosis (asymmetrical division):

  • stimulated by molecular signals for differentiation
  • produces one daughter stem cell and one progenitor daughter cell
  • progenitor cell differentiates into a related specialised cell type, replenishes cells with finite lifespans
• hematopoietic stem cells differentiate into myeloid and lymphoid stem cells
• myeloid stem cells can differentiate into platelets and red blood cells
• lymphoid stem cells differentiate into T and B lymphocytes
• stem cell transplant:

  • adult stem cells obtained from a donor's organ or tissue (injected into patient)
  • eg Parkinson's disease, leukaemia, sickle cell anaemia
  • disadvantage: risk that donated cells will be rejected
• advantages of stem cell transplant:

  • multipotent nature, differentiates into respective specialised cell type, restores function of damaged or diseased tissue
  • self-renewing nature, can constantly replicate to maintain a constant pool of stem cells, repeated treatments not requried
• genetically modified stem cell treatment:

  • removing stem cells from patient, genetically modifying (by expression or no expression of certain genes) or by inserting a normal, functional allele, reintroduce cells into the patient
  • cells can self-renew, proliferate, differentiate for specific functions
• features of zygotic stem cells:

  • totipotent
  • derived from fertilised egg that forms the zygote (cells are produced within the first 3 cell divisions after the egg is fertilised)
• features of embryonic stem cells:

  • pluripotent
  • derived from cells of inner cell mass of blastocyst at about 4 to 5 days post fertilisation
• advantages of using embryonic stem cells:

  • make up a significant portion of the developing embryo, easier to isolate and grow
  • strong ability to self-renew, divides more rapidly, easier to maintain constant supply
  • pluripotent, can produce any cell type, can be used for a wider range of diseases
• disadvantages of using embryonic stem cells:

  • genetically different to cells of potential patients, can lead to immune rejection
  • ethical issues over embryo destruction
• advantages of using adult stem cells:

  • taken from patient's own body, cells genetically identical, avoids immune rejection
  • less ethical consideration
• disadvantages of using adult stem cells:

  • produces limited number of different cell types
  • conditions for self-renewal in labs only identified for a few tissue stem cell types
  • found in small numbers, difficult to isolate
  • not effective for genetic disorders since DNA of stem cells will also carry mutations
• Ethical arguments against use of embryonic stem cells:

  • embryo has potential to be human, can be considered murder to destroy
  • use is as if treating embryo as a source of spare parts
  • expensive
  • may lead to abuse of usage if human status is denied to embryos, may extend to other categories of humans
  • unknown long term health effects, immunological reactions, risk of tumour formation
  • donation and consent issues
• Ethical arguments for use of embryonic stem cells:

  • can potentially treat a wide range of diseases (can grow indefinitely in labs and differentiate into almost all tissues)
  • embryos are not equivalent to human life
  • surplus embryos that can be used for research would be destroyed or stored for long periods of time
• Induced pluripotent stem cells (IPSCs)

  • differentiated adult somatic cells can be reprogrammed to become pluripotent stem cells (eg transcription factors can be used to promote transcription of genes that were inactive/silenced, were condensed before)
• advantages of IPSCs:

  • does not generate or destroy human embryos
  • can be easily obtained from any type of adult cell without risk to donor
  • derived from patient's own cells, will not be rejected by immune system upon transplantation
  • allows generation of pluripotent stem cell lines from patients with inherited diseases to be used in research
• disadvantages of IPSCs:

  • low efficiency
  • usage of retroviruses when undergoing genetic modifications, may pose cancer risk (one of the 4 reprogramming genes is a proto-oncogene, may lead to overexpression)
  • ethical concerns over creation of embryos from IPSC-derived sex cells