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PATH3308 > 4. Therapeutic Adult Stem Cells > Flashcards

4. Therapeutic Adult Stem Cells Flashcards

1
Q

What is a stem cell?

A

Unspecialied cell capable:

Self rewnel

Proliferation

Differentiation into multiple linages

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2
Q

What is the potency heirachy?

A

Totipotency - (Zygote)

Pluripotent - (Inner cell mass)

Multipotent - (Neural SCs, Haematopoetic SCs)

Unipotent - (Commited progenitors, blood cells etc)

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3
Q

What are Adult Stem cells?

A

Stem cells of specific tissues

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4
Q

What do adult stem cells do?

A

Replenish different mature cell types

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5
Q

Where in the tissue are ASCs usually located and how often do they divide?

A

They are usually quiescent in the niche

Divide infrequently (Form one stem cell along with a rapidly cycling progenitor)

Progenitor forms cells of tissue

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6
Q

Adult stem cells are known for expressing plasticity, what does this mean?

A

They have the ability to cross over their identity from one organ to another

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7
Q

What two fields are ASCs used extensively in?

A

Cell therapy

Tissue engineering

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8
Q

What is the stem cell niche?

A

Specialized + restricted micoenvironment

Integrates signals

Maintains pool of quiescent stem cells

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9
Q

What are some extrinsic signals maintaining stem cells?

A

Local microenvironment

Soluble growth factors

Cell-ECM interaction

Mechanical factors

Cell-cell contact

Neural inputs

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10
Q

What are some intrinsic regulators of stem cell fate?

A

Instructive control

Selective Control

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11
Q

What is the process for extrinsive tissue formation?

A
  1. Increase in ECM turnover + thinning = stretch of tissue
  2. Stretched cells responsive to soluble growth factor and proliferate
  3. Increase in epithelial cell mass and new ECM causes bud formation
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12
Q

What is the difference between instructive and selective control?

A
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13
Q

What types of cells do Hematopoietic stem cells give rise to?

A

Myeloid (WBC, RBC, platelets)

Lymphoid

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14
Q

Where can you get Hematopietic stem cells from?

A

Bone marrow

Peripheral blood

Umbilical cord blood

Fetal tissues

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15
Q

What are the surface markers of HSCs in mice?

A

CD34low/-

SCA-1+

Thy1+ (low)

CD38+

C-kit+

lin-

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16
Q

What are the HSC surface markers in humans?

A

CD34+

CD59+

Thy1/CD90+

CD38low/-

C-kit/Cd117+

lin-

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17
Q

What are the clinical applications of HSC transplantation?

A

Autologous transplantation (self donation)

Allogenic Transplantation (recipients need immunosupressive meds, need to be HLA matched)

Treat hematopoietic + immune malignancies (replenish cells after high does chemo)

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18
Q

What are the two major advantages of HSC transplantation?

A
  1. No need to expand cells in culture
  2. No need to reconstitute multi-cellular tissue architecture prior to reimplantation
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19
Q

What are mesenchynal/stromal stem cells?

A

Non-hematopoietic cells residing in bonem arrow and other adult tissues

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20
Q

What lineages do mesenchyma stem cells differentiate into?

A

Mesoderm but can also have endodermic and neuroectodermic potential

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21
Q

Are MSCs a heterogenous population?

A

Yes

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22
Q

Can MSCs be expanded in vitro without loss of differentiation?

A

Yes

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23
Q

What markers are MSCs positive for?

A

CD29

CD44

CD54

CD71

CD73

CD90 (Thy1)

CD105

Cd106

CD271

GD2

Stro-1

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24
Q

What do MSCs do?

A

Secrete ECM, cytokines, growth factors, chemokines

Repair of damaged cells

Maintenance of HSC niche

Immunomodulatory/supressive properties

25
Q

What are the three examples of terminal tissue types that MSCs differentiate into?

A

Adipocyte

Chondrocyte

Osteoblast

26
Q

What are the roles of adipocytes?

A

Space filler in marrow

Lipid metabolism

Energy reservoir

Support differentiation of other cells

27
Q

What function changes do MSCs undergo when differentiating to adipocytes?

A

BMP signalling

High cell density

Cell shape

28
Q

If you have some MSCs and want to turn them into adipocytes, what should you put in the media?

A

1-methyl-2-isobutylxanthine

Dexamethasone

Insulin

Indomethacin

29
Q

What molecular phenotypic markers are associated with adipocytes?

A

C/EBPa

PPARy

Adipocyte P2

Lipoprotein Lipase (LPL)

30
Q

What is the primary signalling molecule for differentiation of MSC to adipocyte?

31
Q

What is the transcription factor involved in adipocyte differentiation?

A

C/EBPB and PPARy

32
Q

Difference between MSCs and OBs?

A

BMP, TGFB, FGF, PDGF

Low cell density

Cell shape

33
Q

When do OBs become OCs?

A

When they become trapped in lacunae

Become mechano-sensors of bone

34
Q

How are MSCs differentiated to OBs in vitro?

A

Dexamethasone

B-glycerophosphate

Ascorbic Acid

35
Q

What are the molecular phenotypic markers of OBs?

A

Runx2

Alkaline Posphatase (ALP)

Bone sialoprotein (BSP)

Osteopontin

Osteonectin

Osterix

Collagen Type 1

36
Q

What is the essential transcription factor for osteogenesis?

37
Q

What is the primary signalling pathway for osteogenesis?

A

The BMP pathway

38
Q

What influences differentiation of MSCs to chondrocytes?

A

TGFB signalling

Sox-9 TF

39
Q

What do you put in media to turn MSCs into chondrocytes?

A

TGFB

Ascorbic Acid

Dexamethasone

High glucose

Proline

Pyruvate

40
Q

What are the molecular phenotypic markers for chondrocytes?

A

Collagen types, 1, 2, X and XI

Sox-9

Aggrecan

COMP

Elastin

41
Q

What is the primary signalling pathway for the differentiation of chondrocytes?

42
Q

What is the essential transcription factor for chondrogenesis?

43
Q

What are some therapeutic uses of MSCs?

A

MSC Transplantations

Graft-versus-host disease (GVHD)

Osteoporosis

Combined therapy with HSC transplantation

Tissue engineering

44
Q

What are some problems associated with MSC use?

A

Cells enter sensecence associated growth arrest (limited ability to generate large numbers)

Use xeno free protocol for culturing

45
Q

Why did the US-FDA recently restrict clinical use of ESCs?

A

For tumorigenic and ethical drawbacks

46
Q

Why are MSCs beign increasingly used?

A

Ease of preparation

Immunologic and ethic advantages

47
Q

What types of diseases are stem cells currently being used for?

A

Congestive Cardiac Failure

Refractory Angina

Acute Thoracic Spinal Cord Injury

Chronic Thoracic Spinal Cord Injury

Corneal Disease

Macular Degeneration

Diabetes

Stroke

48
Q

What stem cell is looking to be better in treatment of cardiac disease?

A

The MSC as it is less immunogenic and can differentiate into cardiomyocytes

49
Q

What companies are working on stem cells for cardiac disease?

A

Mesoblast, phase 3 trial approval

50
Q

What company is working on Acute thoracic SCI?

A

Geron Corp

51
Q

What cell type are geron-corp using for Acute thoracic SCI?

A

Human ESC-derived oligodendrocyte progenitor cells (GRNOPC1)

52
Q

What company is using Human Neural Stem cells (HuCNS-SC) to treat spinal cord injury?

A

StemCells Inc

53
Q

Who is using limbal epithelial stem cells to replace damaged/diseased cornea?

54
Q

What studies are involved in macular degeneration?

A

Advanced cell technology

55
Q

Who is conducting studies into MSC use in diabetes treatment?

56
Q

What company is using NSC cells for stroke treatment?

PATH3308 (21 decks)

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