Ch 3 - Stem Cells and Regenerative Medicine Flashcards

1
Q

List the three main classes of naturally occuring stem cells

A
  • Embryonic stem cells (ESC)
  • Adult Stem Cells (ASC)
  • Foetal/perinatal stem cells (FSC)

4th category - Induced pleuripotent stem cells (IPSC)

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2
Q

List and describe the different types of potency of stem cells

A

-** Totipotent** - Can differentiate into cells from each of the germ layer lineages (endoderm, mesoderm, ectoderm) as well as extra-embryonic tissue
-** Pleuripotent** - Capacity to differentiate into cells from more than one germ layer lineage but NOT extraembryonic tissues
- **Multipotent **- Differentiation is restricted to the germ layer lineage from which they originate

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3
Q

List concerns regarding the use of embryonic stem cells

A
  • Ethical concerns regarding harvesting
  • Tumourigenic potential of teratoma formation when implanted into immune compromised adult animals due to dysregulated cell division and differentiation
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4
Q

List the three best-characterisied examples of adult stem cells

A
  • Haematopoietic stem cells
  • Mesenchymal stem cells
  • Neural stem cells (dentate gyrus of the hippocampus)
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5
Q

Where are perinatal stem cells harvested from?

A

-Umbilical cord
- Amniotic fluid
- Foetal membranes

These are multipotent but may have superior expansion potential, increased plasticity and superior immune privilages when compared to ASC

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6
Q

How are induced pleuripotent stem cells generated?

A

By directly reporgramming adult somatic cells. Retroviral and lentiviral vectors most commonly used (risk of insertional mutagenesis or oncogene transformation). Adenoviral and sendai viral vectors have been successfully used for integration-free viral delivery to overcome these issues

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7
Q

Where do mesencymal stem cells reside?

A

In all adult somatic tissue in perivascular locations

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8
Q

Describe the 2 morphologically diverse mesencymal stem cell populations within a single colony

A
  • Small, rapidly self-renewing cells (RS cells)
  • Larger, more slowly replicating cells

RS cells are superior at slineage-specific differentiation and predominate for the first 4-5 passages/replication cycles

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9
Q

List the 4 features which define a mesencymal stem cell

A
  • Adhere to tissue culture plastic and exhibit a spindle-shaped appearance
  • Form colonies of cells from single parent cells
  • Express a specific set of surface marker proteins that exlude it from haematopoeitic lineages
  • Ability to differentiate into osteoblasts, adipocytes and condrocytes (i.e trilineage differentiation)
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10
Q

What features of mesenchymal stem cells make them excellent candidates for regenerative medicine?

A
  • Can be isolated from adult tissues
  • Undergo rapid, but not limitless, proliferation to produce massive numbers of cells
  • Unlikely to induce an immune response when used in an autologous manner
  • Produce a number of anabolic and antiinflammatory agents (TSG-6, IL-1ra, PGE2)
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11
Q

What to canine MSCs require to undergo consistent, robust, osteogenic potential?

A

BMP-2

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12
Q

Where are MSCs most commonly isolated from in humans?

In animals?

A
  • Bone marrow aspirates
  • Lipoaspirates

Animals
- Bone marrow aspirates
- Enzymatic digestion of adipose tissue

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13
Q

What is an alternative to culture-expanded mesencymal stem cells?

A

Unprocessed, minimally manioulated preparations of tissues that can be rapidly generated at point of care eg. Bone marrow concentrate (BMC) or stromal vascular fraction (SVC)

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14
Q

What are the options of MSC administration?

A
  • Intravascular infusion (cytotherapy) - less than 5%of cells successfully migrate to location of injury and survive
  • Direct implantation/injection (eg, seed onto a scaffold, intra-articular injection) ‘tissue engineering’
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15
Q

What are the main limitations/concerns regarding mesenchymal stem cell therapy in small animals

A
  • Gaps in knowledge
  • Inherent variability in product
  • Access to facilities and expertise
  • Increasing federal oversight (FDA has banned in humans in many states)
  • Unknown safety - stimulate growth of neoplasms? Increased risk of infection?
  • Administration of IV bolus has risk of microvascular embolisation and ischaemia
  • Current lack of strong evidence
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16
Q

Kadiyala et al…

A

First describes osteogenic and chondrogenic differentiation of bone marrow derived canine MSC

17
Q

2005, Volk et al…..

A

Evaluated osteogenic differentiation potential of marrow-derived MSC in 19 dogs - necessary to supply with BMP-2

18
Q

2008, Neupane et al…

A

Completed most comprehensive characterisation of adipose-derived mesenchymal cells. Tend to proliferate more rapidly, preparation and handling effects proliferation rates

19
Q

2007 Black et al…

A

Evaluated effect of single intra-articular injection of stromal vascular fraction celss in 18 dogs with hip OA - significant improvement in lameness and function at 3m

Follow-up study - Single injection in 14 dogs with elbow OA - outcomes improved 30-40% comapred to baseline

20
Q

Nishida et al…

A

Weekly injections of bone marrow derived MSC into spinal cord lesion causing lack of deep nociception. No complications but no improvement

21
Q

Penha et al….

A

treated 4 dogs with longstanding neuro dysfunction from IVDD with intralesional bone marrow derived MSC. Reportedly improvements at 18m but not changes on MRI and were also having long-term physio

22
Q

Studies evaluation MSC treatment in cats…

A
  • Quimby et al - Safetly of systemically administered adipose derived stem cells to cats with CKD - adverse rxn from allogenic thawed cells at higher dose
  • Webb et al - allogenic MSC for Tx of chronic enteropathy. 5/7 significant improvement or resolution
  • Arzi et al - Cats with chronic gingivostomatitis Tx with 2 injections of autologout adipose derived MSC. 5/7 either complete remission or sunstantial improvement.