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Small Animal Rhab > Regenerative Medicine > Flashcards

Regenerative Medicine Flashcards

1
Q

What is regenerative medicine?

A

Therapies that are capable of re-growing, repairing or replacing damaged cells or organs (usually cell based blood, bone marrow, adipose tissue, fetal tissue)

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2
Q

T/F Stem cell therapy has regenerative capabilities and help in the modulation of inflammatory or immune responses

A

True

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3
Q

Match the following description with the appropriate stem cell classification (totipotent, Pluripotent or multipotent:
Able to differentiate into intra- and extra-embryonic tissue (aka anything)
Found in fertilized zygote

A

Totipotent

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4
Q

Match the following description with the appropriate stem cell classification (totipotent, Pluripotent or multipotent:
Able to differentiate into endoderm, mesoderm, or ectoderm
Naturally found in embryos
Can be reverse engineered from adult induced pluripotent stem cells

A

Pluripotent

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5
Q

Match the following description with the appropriate stem cell classification (totipotent, Pluripotent or multipotent:
Able to differentiate into limited number of cell lines
Found in most adult mammalian tissue

A

Multipotent

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6
Q

T/F by definition totipotent stem cells are also pluripotent and multipotent

A

True also pluripotent are considered multipotent too

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7
Q

Mesenchymal stem cells are _____ (totipotent, pluripotent, or multipotent) and can be obtained from multiples places such as the bone marrow, adipose tissue, muscles, tendons and dental pulp

A

Multipotent

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8
Q

Mesenchymal stem cells are used for what properties/functions

A

Regenerative, anti-inflammatory, immunomodulatory and trophic functions (attract other cells to the location they are placed)

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9
Q

What type of stem cell therapy is commonly used for joint injections?

A

Mesenchymal stem cells

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10
Q

How do you define a stem cell?

A

1) adheres to plastic (important for harvesting)
2) expresses cell surface antigens (CD markers)
3) differentiates into osteoblasts, adipocytes and chondroblasts in vitro

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11
Q

Explain the steps of preparing stem cells

A

1) collection (surgical collection either of adipose tissue or bone marrow aspirate)
2) isolation (gradient density centrifugaiton)
3) expansion (population doubling until sufficient numbers are reached in a cell culture setting)

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12
Q

With normal tissue healing, fibrous scar tissue is produced resulting in decreased function and permanent damage such as decreased range of motion. How would stem cell therapy help address those issues?

A

Stem cells can differentiate into the cell type that of the area undergoing the healing process. By placing new healthy cells into the area, less fibrous scar tissue is laid down resulting in functional regeneration rather than restructuring of existing tissues.

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13
Q

T/F Stem cell therapy has anti- inflammatory properties

A

True
Stem cell therapy produces anti-inflammatory cytokines which can help modulate the inflammatory response- both local and systemic

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14
Q

T/F Stem cell therapy is not considered an immunomodulatory form of therapy

A

False- It can modulate lymphocyte response

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15
Q

T/F because stem cells can be used to produce a variety of tissues and be propagated to produce a larger quantity of those tissues, laboratory settings can use stem cell generated tissues for disease research, disease modeling and drug testing

A

True- SCT can stimulate an in vivo environment and help reduce the amount of live animal lab testing that is being done

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16
Q

T/F In research, stem cell therapy has repeatedly proven through research to help improve the functional outcome of patients with osteoarthritis through its’s anti-inflammatory and regenerative effects.

A

True and false
Too much variability in the studies and they are not able to see if the results are actually reproducible as there are no good control groups.
However, some studies have shown improved functional outcome in cases of elbow and hip OA, the question regarding regeneration of cells in these joints has not been clearly answered or addressed as most studies focus on the anti-inflammatory properties of stem cell therapy

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17
Q

Does stem cell therapy help in cases of bone regeneration?

A

Yes, according to the critical gap model, instances where an entire segment of bone needed to be replaced, using a hydrogel matrix impregnated with stem cells clinically improved the regeneration of the bone faster than normal bone healing.

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18
Q

Rather than taking tendons from another part to fix tendons tears, what does stem cell therapy allow for?

A

Allows for replacement of the tendon using a hydrogel matrix impregnated with stem cells rather than using an autologous tendon graph. Clinically both the hydrogel matrix and the graph heated the same so using a matrix could be a substitute.

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19
Q

IF less than ____% of a CCL is torn in a dog, stem cell therapy can encourage healing and improve the rate of the healing process.

A

50 (only in partial tears)

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20
Q

What is platelet rich plasma prepared from?

A

The patients blood

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21
Q

T/F platelet rich plasma has alpha granules that contain growth factors, cytokines, and chemokines

A

True

22
Q

What is in platelet rich plasma?

A

Platelets, white blood cells and red blood cells

23
Q

The goal of platelet rich plasma is to have a ___-____-fold increase above baseline in platelet levels

A

4-7 (dogs have 150,000 platelets per microliter, goal should be 600,000-1 million platelets per microliter)

24
Q

Why are white blood cells and red blood cells considered controversial in platelet rich plasma?

A

White blood cells can produce pro-inflammatory cytokines (bad) and red blood cells have increased IL-1beta and TNFalpha (also bad)

25
Q

What is one of the downsides to platelet rich plasma, especially in smaller patients?

A

Need to start with a large volume of blood to get the goal concentration of platelets about 60 cc of blood

26
Q

Describe the process of making platelet rich plasma

A

1) collection blood (anticoagulant citrate dextrose-A; ratio of one part anticoagulants to 7 parts blood)
2) prepare the blood in the centrifuge (split platelet rich plasma, platelet poor plasma and RBC)
3) Administer (sterile technique, under sedation)

27
Q

T/F a pro of the Angel platelet rich plasma system is that the platelet rich plasma portion is collected directly into a sterile syringe so you can inject the PRP right away

A

True- yellow portion was platelet poor plasma, pinkish portion was platelet rich plasma and red was RBC

28
Q

How often should platelet rich plasma be administered when using it to treat OA?

A

1-3 injections given at 2 week intervals

29
Q

Describe some of the side effects of platelet rich plasma (specially in treating OA)

A

1) discomfort from injection
2) reaction (d/t intense amount of platelets being injected/# of cytokines)
3) Infection

30
Q

It is recommended to combine platelet rich plasma therapy with rest and rehabilitation. If the dog was previously taking any NSAIDS or steroids these should be discontinued for _____ weeks

A

2

31
Q

T/F Studies show that platelet rich plasma alone to treat OA showed no improvement but PRP plus stem cells showed great improvment

A

F- PRP alone showed improvement at 12 weeks post injection and PRP plus stem cells also had improvement by increasing the extracellular matrix synthesis and chondrocyte proliferation.

32
Q

T/F there is no indication that platelet rich plasma therapy helps with bone healing

A

True multiple studies prove that using PRP for bone healing showed no significant difference

33
Q

T/F platelet rich plasma therapy can help in healing a tendon injury

A

T PRP alone showed subjective improvement and PRP plus stem cells showed an objective improvement in gait

34
Q

Autologous conditioned plasma has (more or less) platelets compared to PRP

A

Less- 2 fold increase in CAP vs 4-7 fold increase in PRP; has shown to increase platelets, PDGF and TGF-beta 1 in dogs

35
Q

T/F the effects of autologous conditioned plasma are similar to using hyaluronic acid plus steroids

A

True

36
Q

Autologous conditioned serum is sometimes referred to as:

A

IRAP II (interleukin-1 receptor antagonist protein)

37
Q

T/F autologous conditioned serum induces WBC to produce pro-inflammatory cytokines

A

F- induces ANTI- inflammatory cytokines

38
Q

What are cytokine?

A

Small soluble proteins that act as intercellular messengers. They are very diverse and have many different properties. They can affect many different cell lines (promiscuity). Can be pro- or anti-inflammatory.

39
Q

The following describes (pro-inflammatory/anti-inflammatory) cytokines:
1) activated synoviocytes, chondrocytes and monocytes
2) up-regulated metalloproteianse gene expression
3) decrease the synthesis of collagen and proteoglycans
4) increase inflammatory mediators
5) causes pain and lameness
6) lead to joint space narrowing and increased joint fluid

A

Pro inflammatory cytokines

40
Q

Interleukin-1 beta (pro inflammatory) requires co-binding with IL-accessory protein. What does interleukin-1 beta lead to?

A

Tissue destruction and inflammation (break down the joint via leukocyte infiltration, increased proteoglycan and collagen degradation, decreased proteoglycan synthesis)

41
Q

Tumor necrosis factor-alpha is a pro-inflammatory cytokines that increases the matrix metalloproteinase and decreases proteoglycans that leads to decreased cartilage extracellular matrix. All of these lead to:

A

The perpetuation of OA (it upregulates the receptors that respond to tumor necrosis factor alpha which worse’s the inflammation —> causes a cycle of upregulating and increased inflammation)

42
Q

The following are examples of (pro/anti-inflammatory cytokines:
IL-1 receptors antagonism (IL-1ra), IL-4, IL-10, IL-13

A

Anti-inflammatory
These are the good ones

43
Q

Describe how IL-1 receptors antagonist (IL-1ra) works to fight iL-1 beta

A

It competitively binds to the same receptor as interleukin 1 beta (pro-inflammatory cytokines); unfortunately IL-1ra needs to be 10-100x higher than IL-1beta to outcompete.

44
Q

How do IL-1, IL-10 and IL-13 work as anti-inflammatory cytokines?

A

1) causes a non-specific decrease in IL-beta and tumor necrosis factor alpha expression (decreases pro-inflammatory cytokine expression)
2) causes an up-regulation of IL-1ra expression
3) causes a decrease in inflammatory mediators

45
Q

What are the steps of making ACS (autologous conditioned serum)?

A

1) collect the blood (sterile technique, collect with butterfly catheter into commercial syringe)
2) incubate (37 Celsius, 7 hours for 10 mL syringe)
3) Centrifuge (sterile tech, collect serum, store at -20 until needed)

46
Q

T/F once ACS has been processed and frozen it must be used within one month

A

F once you freeze the sample it is good indefinitely until you need it. Once you thaw it out it has to be used

47
Q

T/F IRAP II tubes work by utilizing the properties of borosilicate spheres which cause a foreign body reaction in the sample causing WBC to bind to the beads. Then anti-inflammatory cytokines develop.

A

True
If you wait too long, the production of pro-inflammatory cytokines begins, this is why the incubation period is defined for collecting and processing the sample you need to freeze the sample before the pro-inflammatory cytokines are produced.

48
Q

T/F IRAP II/ACS is equally effective across species.

A

F causes a 3-140 fold increase in IL-1ra in humans, 93-119 fold increase in horses, and only a 5-40 fold increase in canines; 10-100x increase of IL-1ra is needed to block the binding of IL-1B

49
Q

T/F there is a dose-dependent improvement in gross and histological scores regarding cartilage lesions in canines treated with IRAP II (autologous conditioned serum)

A

True

50
Q

The best therapy for tendon healing is (stem cell therapy/ platelet rich plasma therapy)

A

Both
Stem cells and PRP may work synergistically

Small Animal Rhab (12 decks)

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