What is regenerative medicine?
repair of functionally compromised cells; tissues or organs by biological substitutes or stimulation of endogenous process
What are the advantages of using primary cells?
autologous
what are the disadvantages of using primary cells?
limited availability; low yield; poor growth rate
What is self-renewl?
a cell divides to generate daughter cells equivalent to the mother cell
What is cell potency?
rang of differentiation options availble to a cell?
Waht is a totipotent cell?
has the capacity to form an entire organsim
Give an example of a totipotent ell?
zygote
What is a multipotent cell?
can form multiple cell types that constitute the entire tissue or tissues
What is a pluripotent cell?
ablt to form all the body’s cell lineages including germ cells
What can pluripotent cells not generate?
placenta and embryo
Give an eample of a multipotent cell?
haematopoietic stem cell
Give an example of a pluripotent cell?
human embryonic stem cell
Where are adult stem cells found?
tissue specific- only localise in one specific region of the tissue
What is the self-renewal capacity of adult stem cells?
niche-dependent (the environemtn of hte specific area where they are located), capable of life long self-renewal
Waht type of cell are adult stem cells?
multipotent
What tumour are adult stem cells not able to form?
teratoms
Where are hair follicle stem cells found?
only in bulge region of hair follicle
Where are intestinal stem cells found?
only at bottom of crypts
Where are haematopoietic stem cells found?
long-term stem cells: close to osteoblasts; short-term stem cells: mear to blood vessels
What were mesenchymal stem cells originally named stem cells?
a class of cells from human bone marrow and periosteum that can be isolated and expanded in cultre and induced to form a variety of mesodermal phenotypes and tissues
What is thought to be the function of mesenchymal stem cells now?
immunomodulatory and trophic- not multipotent stem cells
What were mesenchymal stem cells orginially named?
a subpopulation of bone marrow cells that can generate bone, cartilage and adipocytes in vitro–then it was thought that these bone marrow stromal cells could form other mesodermal tissues
What is the advantages of adult stem cells in regernative medicine?
can be autologous; ready to use
What is the disadvantge of using adult stem cells in regenerative medicine?
limited expansion; resitrcted cell potency- cannot generate all cell types
Where are pluripotent stem cells from in regenerative medicine?
inner cell mass of pre-implantation embryos -ESCs or from manipulation of somatic cell types- induced PSCs
What is an embryoid body?
aggregate of PSCs that have differentiated into the germ layers
What is the advantages of ESCs or PSCs in cell therapy?
can be expanded to a lrge amount of cell;s capable of generation of all cell types
What are the challenges of using ESCs or PSCs in cell therapy?
differentiation of specific cell types (what environment?) ; integration and survival of cells in vivo; immune rejection; tumorigenesis
How are PSCs induced to differentiate?
medium supplementation; co-culture; gene transduction
How can immune rejection be reudced?
stem cell bank; immune suppression; immune tolerance; reprogramming patietns own cells to pluripotent stem cells
How is tumorigenesis prevented?
generation of iPSCs without changing genomic DNA; optimal hPSC culture conditions (maintain genomic stability); eliminating undifferentiated hPSC before transplantation e.g by FACS sorting; suicidal hPSC derived cells
What are the features of suicidal hPSC-derived cells?
put a toxic gene and if the cell transforms the promoter turns on toxic gene to kill the cell
What factors can facilitiate direct conversion of fibroblasts to functional neurons?
Ascl1; Brn2; Mytl1
What is a pluripotent cell?
differentiate into itssue from all 3 germ layers
What is a multipotent stem ell?
can differentiate into tissue derived from a single germ layer
What potency do tissue-resident stem cells have?
oligopotent as can form terminally differentiated cells of a specific tissue
What 2 types of tissue do totipotent cells form?
embryonic and extra-embryonic tissue
What are unipotenet cells?
can self renew and differentiate into only one specific cell type and form a singel lineage
What does the outer cell mass of the blastocyst form?
the placenta
What transcription factors can help identify embryonic stem cells?
Nanog and Oct4
What is the function of Nanog and Oct4?
maintain the stem cells in an undifferentiated state, capable of self-renewal
What is an embryoid body?
all 3 germ layers are present in
What culture conditions maintain ESCs in an undifferentiated state?
feeder layer of embryonic fibroblast cells or medium that contains the anti-differentiation cytokine leukaemia inhibitory factor
What is the function of a stem cell niche where tissue-resident stem cells reside?
a microenvironemnt that controls the self-renewal and differentation of the tissue resident stem clels
What state are the majority of tissue -resident stem cells usually in?
dormant until are activated by specific signals during injury and repair
What is symmetrical cell division?
stem cell division that results in identical daughter cells
Why is stem cell homeostasis important?
uncontrolled increase in stem cell proliferation could lead to hyperplasia or carcinogenesis while a reduction in stem cells would impair organ repair
What is asymmetric division?
stem cell geenrates an identical daughter cell and a second differentiated daughter cells
What is the function of asymmetric divison?
allows for organ repair and regeneration while maintaining a population of stem cells
What cells are iPSCs produced from?
adult somatic cells
What transcription factors are needed for the production of iPSCs?
Oct3/4; Sox2; Klf4 and c-Myc
What is used to introduce the reprogamming factors into adult cells to produce iPSCs?
retroviral vectors
How do adult stem cells promote repair of tissues?
secrete molecular mediators with anti-apoptotic, immunomodulatory, angiogenic and chemoattractant properties