stem cells Flashcards
what is endogenous repair + what is 1 eg:
the intrinsic ability for cells to proliferate + develop into mature functional progeny
- signals come from cellular microenvironment
eg:
1) liver regeneration
what is a barrier to using stem cells as cellular therapy
- tissue from self is transferred to another part of body
- BUT; if tissue from another person is transferred; there are IMMUNOLOGIC BARRIERS
(HLA-human leukocyte antigens + T cells)
what does a bone marrow transplant mean
- replace bone marrow with healthy cells (from ur own tissue or from donor tissue
- cancer or cancer treatment = damages hematopoetic stem cells (cells that become blood cells) (found in bone marrow)
what are some important characteristics of stem cells
- single cells that can SELF RENEW
- can differentiate into all functional cells of a tissue
- other features:
1) rare
2) quiescent (not in active state)
3) may be resistance to cytotoxic stress (chemo/radiotherapy)
4) may be identified by specific genes / surface protein combinations
what is the role of stem cells in intestinal crypts?
- express LGR5+ gene = able to develop into all cells that contribute the intestinal crypt
- every tissue has its own mechanism of repair/homeostasis/regeneration = some use stem cells, some dont
1) those tissues that dont use stem cells to repair/homeostasis = can proliferate into mature functional cells, but UNABLE to regenerate the entire ORGAN
2) tissues that use stem cells:
- stem cells are in QUIESCENT state
- can be enriched/identified by their specific markers
what does it mean when we say ‘tissues have pre-determined response to disease / injury’
- the way tissue repairs depends on the type of disease / injury
can include:
1) making new functional cells
2) FIBROSIS = caused by inflammatory response to disease/trauma/cell death
- (does not make new functional cells- scarring)
what is immunophenotype
- to enrich OR identify stem cells based on SURFACE MARKERS (specific genes / surface protein combinations)
what are some complications of hematopoetic stem cell transplantation?
1) chemo/radiotherapy (Total body irradiation)
- haemorrhagic cystitis (inflammation of bladder)
2) transplant specific complications
What are some types of haematopoeitic stem cell transplants
1) bone marrow harvest (traditional collect bone marrow from volunteer)
2) G-CSF (cytokine) mobilisation = moves HSC from bone marrow to peripheral blood
- stimulates neutrophil production
3) umbillical cord blood stem cells
- umbilical cord contains stem cells (can be stored after give birth)
what are the 2 types of Hematopoetic stem cells transplant approaches used to treat blood disease
autologous + allogenic
1) autologous = HSC comes from patient
- HLA- identical
- can use higher dose of CHEMO (but hard for neutrophils to recover, but using self stem cells is FASTER = reduces damage)
2) allogenic = HSC comes from donor
- requires HLA matching
- risk of graft vs host disease
- use immunosuppression after transplantation
what is the purpose of transplant conditioning? (2)
- used before a Hematopoetic stem cell transplant
- regime depends on patient (age, comordibities…..)
1) immunosuppresion = to prevent graft rejection
2) reduce tumor burden
what is graft vs host disease and how can it occur?
- occurs from allogenic stem cell transplants (patient gets stem cell transplant from donor/donated umbilical cord blood)
- where the donated stem cells view the recipient’s body as foreign = start attacking the host body
how can HSC treat blood disorders (sickle cell anemia)?
1) sickle cell anemia = makes defective Hb (of rbc) = ause rbc blockage
- gene mutation = V6G substitution on B-globin chain
= but if bone marrow is replaced = can start making normal Hb
what are some complications to treating sickle cell with HSC?
1) acute pain syndrome
2) acute chest syndrome
3) vascular occlusion (stroke, blindness, priapism)
4) acute haemolysis
5) pure red cell aplasia
6) hyposplenism
how can H stem cells treat B-globin sickle cell disease ?
- B-globin sickle cell disease = mutation in B-globin gene
- allogenic HSC transplant
- use CRISPR/CAS9 to achieve homologous recombination at the B-globin gene locus in HStemCells
= correct mutation of Glu6Val mutation responsible for sickle cell disease = express normal adult B-globin
