Insulitis Flashcards
Insulitis
Infiltration of lymphocytes in pancreas
CD8+s kill beta cells with granzymes and perforin
Response increases as insulin concentration decreases
CD20+ B cells cause insulin desensitivity
Islet transplants
Stop severe hypos 6-10 year benefit Need immunosuppressants Require low level insulin injections Non invasive Needs donors
Induce pluripotent stem cells
Ulimited supply, easy to obtain Less ethical issues, adults not embryos Difficult to do Personalised so no immunosuppressants Carcinogenic (teratomas)
What factors reprogramme skin cells
OCT4, SOX2, KIF4, C-MYC
Embryonic stem cells
Inner cell mass of blastocyst Ethical issues Autoimmune responses, teratomas Potentially unlimited supply - self-renewal Multidirectional differentiation
What are the two routes for transdifferentiation?
Convert liver cells to beta cells
Covert alpha to beta cell
Liver to beta cell transdifferentiation
Inject mouse with virus and TFs
Produce insulin positive cells
Alpha to beta cell transdifferentiation
GABA induces alpha cell mediated beta-like cell neogenesis
Pancreatic stem cells
Partially differentiated
Difficult to isolate
Hepatic stem cells
Autologous source
Difficult to produce enough
Spermatogonial stem cells
Potentially unlimited supply
No ethical issues, very plastic
No long term studies
Mesenchymal stem cells
Unlimited supply
Multidirectional differentiation
Autologous
Temporary
Beta cell regeneration
Enhanced replication of existing beta cells
Form new cells from cells not expressing insulin
Transdifferentiation or neogenesis (from progenitors)
Smart insulin features
Inactive when glucose is normal/low
Rapidly activated when glucose rises
Rapidly inactivated when glucose falls
Microarray patches
Insulin in polymer that dissociates in hypoxic environments (high glucose) releasing insulin