11: transplantation

Question 1

neurons have to? cell replacement techniques represent? clinical implications for?

Answer 1

have to carry out function for entire life, aren’t replaced if damaged. one of the advanced methods by which we can ameliorate dysfunction of lesioned/damaged brain. NDDs like AD, PD for which no adequate medical treatments are avail

Question 2

5 essential elements of neuronal transplantation?

Answer 2

donor age. host age. vascularization. immunologic factors. target access.

Question 3

donor age

Answer 3

transplanted tissues survive best when from active stage of embryogenesis

Question 4

host age

Answer 4

old age drastically reduces survival and fiber outgrowth of graft

Question 5

vasculrization for neuronal transplantation?

Answer 5

development of adequate blood supply to the graft is one of the most important factors determining graft survival

Question 6

brain: immunologically? leads to? survival of graft enhanced by?

Answer 6

brain is an immunologic privileged site, leads to delyaed immune response to grafted tissue. by using immunosupressants

Question 7

target access for neuronal transplantation? where should you always put the graft?

Answer 7

appropriate target area influences graft survival + growth of grafted tissues. always place at terminal area/target site, not the site of cellular origin

Question 8

3 methods of neuronal transplantation

Answer 8

transplantation of: embryonic tissues, genetically modified cells, polymer-encapsulated cells

Question 9

transplanation of embryonic tissues: what

Answer 9

solid pieces of tissues in preformed cavity or cell suspension of embronic tissues injected into target area

Question 10

transplanation of embryonic tissues: 2 advantages + disadvantages

Answer 10

A: good graft survival, regulated release. D: ethical issues, limited avail of fetal tissue

Question 11

transplanation of genetically modified cells: two cell types? mos commonly used method?

Answer 11

primary cells + immortalized cells. most commonly used: retroviral infection, which yields high levels of transgene incorporation

Question 12

transplanation of genetically modified cells: 2 advantages + disadvantages

Answer 12

A: trasnplantation of specific genes. no ethical issues. D: unregulated secretion. poor survival of graft

Question 13

transplanation of genetically modified cells: two classes of genes usually used

Answer 13

grwoth factors: cells genetically modified to produce GDNF, prevents degeneration of DA neurons (for PD). affected NT enzymes: cells genetically modified to produce TH, L-DOPA can ameliorate deficits in PD

Question 14

transplantation of polymer encapsulated cells: is what? comprises what? what cells?

Answer 14

delivers growth factors/NTs to discrete brain areas. a selective barrier that allows free transport of low but not high MW agents. encapsulated PC12 cells, for animal models of PD

Question 15

PC12 cells

Answer 15

produces NA + DA. immortalized rat chromaffin cell that releases NA + DA. used for transplantation of polymer encapsulated cells for animal model of PD

Question 16

transplantation of polymer encapsulated cells: 3 adv? 1 disadv?

Answer 16

use of unmatched tissue, no danger of tumor formation, can be retrieved in case of detrimental effects. D: unregulated secretion

Question 17

2 animal models of PD

Answer 17

unilateral lesion of nigrostriatal pathway with 6 -hydroxydopamine. bilateral lesion of nigrostriatal pathways with MPTP

Question 18

6 hydroxydopamine: what lesion induced changes do you see (+ drugs)?

Answer 18

loss of DA neurons triggers drug induced sterotypical rotational behaviour. apomorphine, DA agonist = contralateral while amphetamine = ipsilateral rotation