Mesenchymal Stem Cells

Question 1

What are mesenchymal stem cells?

Answer 1

• similar to fibroblasts under a microscope
• progenitors to fibroblasts -> can differentiate
• can traffic around the body

Question 2

What are the main properties of MSCs?

Answer 2

multipotent cells

can self renew

can differentiate into other mature stromal cells

Question 3

What are the features of bone marrow MSCs?

Answer 3

(+) highest immunomodulatory capacity
- good for chondrogenic (cartilage formation) and osteoblastic differentiation

(-) difficult to isolate and low numbers obtained

Question 4

What are the features of adipose tissue MSCs?

Answer 4

(+) retain naive phenotype in culture longer, best for adipogeneic differentiation

(-) reduced chondrogenic and osteoblastic potential, might have pericyte like qualities

Question 5

What are the features of umbilical cord MSCs?

Answer 5

(+) grow easily = good for expansion, easy to obtain, more mobile, best for neural cell differentiation

(-) not always effective in inflammation models, ethical issues

Question 6

What are the defining characteristics for MSCs?

Answer 6

must be adherent

must be able to differentiate into osteoblasts, chondrogenic cells and adipogenic cells

must be immunosuppressive

Question 7

What are the advantages of MSCs?

Answer 7

• express low levels of MHC I and MHC II
• secrete immune modulatory factors
• promote tissue repair

Question 8

How do MSCs modulate the immune response?

Answer 8

-inhibit T cell proliferation, alters CD4 T cell balance and reduces CD8 activity
-promote tolerogenic DCs which promote immune tolerance and stop a harmful immune response + decrease pro inflammatory factors
- reduces pro inflammatory macrophages and promotes anti inflammatory macrophages

Question 9

What are MSCs activated by?

Answer 9

pro inflammatory cytokines in tehir environment

Question 10

How can msgs be used in personalised medicine?

Answer 10

1) MSCs are removed from the body
2) MSCs are grown to large numbers in the lab
3) They are then injected back into the body

Question 11

What are the potential advantages of using MSCs over standard drug treatment?

Answer 11

• less side effects
• can be anti inflammatory and promote repair

Question 12

How are MSCs used in islet cell transplantation?

Answer 12

1) islet cells are transplanted with MSCs/ are co cultured with MSCs before transplantation
2) MSCs suppress the immune response and provide an anti inflammatory environment by produced IL-10 and TGF-B, they also promote tissue repair

Question 13

What are the advantages of using MSCs in islet transplantation?

Answer 13

• immunomodulation
  -reduction of autoimmune responses
• increased islet survival

Question 14

What are the disadvantages of using MSCs in isle transplantation?

Answer 14

• limited long term effectiveness
• procedure is complex
• potential immune reaction to MSCs

Question 15

How are MSCs used in nerve regeneration?

Answer 15

-they promote axonal regeneration and remyelination
-they’re used to reduce inflammation and enhance neuronal survival in spinal cord injuries

Question 16

What are the issues with MSCs therapy?

Answer 16

-cell based therapy= not a readily available source of cells
- ethical issues= cells com from bone marrow
- cells grown in culture lose their immunomodulatory properties

Question 17

What can altering the culture environment do for MSCs?

Answer 17

• alters gene transcription and physiological functions for the cell

Question 18

What is IDO?

Answer 18

an enzyme that breaks down tryptophan into kynurenine

Question 19

How do MSCs affect T cell proliferation?

Answer 19

they deplete tryptophan which inhibits T cell proliferation

Question 20

How can exosomes be used in therapy?

Answer 20

they can be harvested from MSCs and injected into the affected area

Question 21

How can MSCs be used to treat cancer?

Answer 21

they can be engineered to overexposes proteins of interest that can then be collected and used for therapy

/or

they can secrete toxic drugs to kill cancer

Question 22

When can MSCs become pro inflammatory?

Answer 22

• when incubated with TLR4 and TLR9 ligands

Question 23

What negative role can MSCs play in cancer?

Answer 23

can become cancer associated fibroblasts
can suppress local immunosuppression and drive tumour development
can drive activation of cancer cells to become aggressive and metastasise