CSB332H1 Lecture Notes - Lecture 18: Adipose Tissue, Umbilical Cord, Cell Potency

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14 May 2018
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Lecture 18(a): Extracellular Vesicles & Alzheimer’s Disease
What is Known…
Neuronal stem cells migrate to damaged areas, however they are not incorporated to form
new neuronal networks
o Acute stroke, and long term functional recovery we do not have efficient mechanisms
ð Currently there are two FDA approved mechanisms to eliminate plaques/thrombus:
1. Tissue Plasminogen Activator (TPA):
§ Drug that functions to break up a clot found within our blood vessels
2. Surgery:
§ Mechanically go into one of the femoral veins into the area of the brain with
the clot and physically remove it
Extracellular Vesicles (EVs):
o EVs are shed from membranes of different type of cells (all cells within the CNS);
microvesicles, exosomes & apoptotic bodiescontain different RNAs/factors/proteins
§ Therapeutic development of EVs is being explored for regenerative scenarios
– different technique when compared to stem cells
Stem cells function to divide, differentiate, cannot increase in their
dosage easily, cannot be easily stored
EVs once delivered will be capable of carrying out variable functions,
can increase their dosage, can be stored in fridges
o EV cargo are cell type specific: various biological properties
o Mesenchymal stem cells (MSCs) are capable of producing extracellular vesicles
§ EVs were systemically administered to rodent stroke models and produced
behavioral improvements , did not display reductions in infarct volume
Mesenchymal Stem Cells (MSCs):
Multipotent stem cells not part of the nervous system they are present in multiple tissues:
(1) Umbilical cord (2) bone marrow (3) adipose tissue
o MSCs self-renew by dividing and can differentiate into multiple tissues including:
§ Bone, cartilage, muscle, fat cells, and connective tissue
ð MSCs positively impact the nervous system – affects cell survival after damage (i.e. stroke)
o Expected to find MSCs in the area of lesion, however after systemically injected labeled
MSCs they were found in the lungs
§ Therefore, MSCs have a bystander effect: they release other factors (i.e. EVs)
to complete their function, stem cells themselves are not affecting cell survival
Advantages of MSCs:
Easily accessible – adipose tissue
Promote functional recovery and modulate immune responses
Ability to migrate to injured sites? – NO false, they have bystander effects
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Document Summary

What is known : neuronal stem cells migrate to damaged areas, however they are not incorporated to form new neuronal networks, acute stroke, and long term functional recovery we do not have efficient mechanisms. Currently there are two fda approved mechanisms to eliminate plaques/thrombus: tissue plasminogen activator (tpa): Drug that functions to break up a clot found within our blood vessels: surgery: Therapeutic development of evs is being explored for regenerative scenarios. Evs were systemically administered to rodent stroke models and produced behavioral improvements , did not display reductions in infarct volume. Bone, cartilage, muscle, fat cells, and connective tissue. Mscs positively impact the nervous system affects cell survival after damage (i. e. stroke: expected to find mscs in the area of lesion, however after systemically injected labeled. Therefore, mscs have a bystander effect: they release other factors (i. e. evs) to complete their function, stem cells themselves are not affecting cell survival.

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