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Intro to Surgery > Lecture 12 - Regenerative & Biological Therapy > Flashcards

Lecture 12 - Regenerative & Biological Therapy Flashcards

1
Q

What is regenerative medicine?

A

Branch of translational research which deals with the process of replacing, engineering, or regenerating human cells, tissues, or organs to restore normal function.

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2
Q

Do products currently available in veterinary medicine actually “regenerate” tissue during healing?

A

Usually, no.

Remains unclear or unproven in many applications.

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3
Q

What are most currently available regenerative therapies aimed at?

A
  1. Reducing inflammation
  2. Promoting neovascularization
  3. Modulating and promoting an anabolic local environment during healing.
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4
Q

What are currently available regenerative therapies NOT aimed at?

A

Direct regeneration of tissue via direct inoculation of a stem cell.

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5
Q

What is a better term than “regenerative therapies” for the therapies that are currently available?

A

biological therapies

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6
Q

Predominant indication in small and large animal medicine is the treatment of _____.

A

musculoskeletal disease

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7
Q

What 2 aspects of musculoskeletal disease are biological therapies most used for?

A
  1. Joint/osteoarthritis
  2. Tendon and ligament injury
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8
Q

What additional areas have ongoing research in veterinary medicine?

A
  1. Pulmonary repair
  2. Oncology and cancer therapy
  3. Dermatology
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9
Q

What does IRAP mean/stand for?

A

Autologous Conditioned Serum

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10
Q

What does PRP stand for?

A

Platelet Rich Plasma

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11
Q

What does “pro-stride” mean?

A

Autologous Protein Solution

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12
Q

What are 4 locations from where we can get stem cells?

A
  1. Bone marrow aspirate concentrate
  2. Bone marrow-derived MSCs
  3. Fat/Vascular Stromal Fraction MSCs
  4. Autologous vs. Allogenic
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13
Q

What is autologous conditioned serum (IRAP) widely used for?

A

Equine sports medicine (for the last 15-20 years)

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14
Q

What does IRAP mainly use in its MOA?

A

Cytokines

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15
Q

What are cytokines and what are the 2 general types?

A

Proteins within mammals that are secreted by various cells of the immune system that influence an effect on another cell.

Types = Pro-inflammatory and Anti-inflammatory

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16
Q

What is the most common and central pro-inflammatory cytokine?

A

IL-1

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17
Q

How is IL-1 involved in osteoarthritis?

A

It is upregulated in the joint and increases proteolytic enzymes (matrix metalloproteinases) which degrade type-2 collagen in articular cartilage.

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18
Q

What is one anti-inflammatory cytokine involved in IRAP and what is another name for it?

A

IL1-ra; AKA IRAP protein

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19
Q

Where does IL1-ra originate from?

A

monocyte cells in the blood

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20
Q

What does IL1-ra bind to and why?

A

Binds to IL-1 receptors to block cellular signaling of inflammation.

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21
Q

What does IL1-ra circulating in the blood do?

A

Normal amounts of circulating IL1-ra helps provide balance between anabolic (build/restore) and catabolic (breakdown) processes in the body.

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22
Q

IRAP binds to _____, preventing _____ binding which would cause _____.

A

IL-1 receptors, IL-1, inflammation

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23
Q

How do we capitalize on IL1-ra as a biological therapy?

A

Collect whole blood from animal. expose it to select surfaces to stimulate monocytes to secrete IL1-ra.

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24
Q

How can blood monocytes be stimulated to secrete IL1-ra?

A
  1. Borosilicate or chromium sulfate glass beads in a syringe
  2. Held at body temp (37.5 deg C) for up to 24 hours
  3. Centrifuged and serum aspirated off
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25
Q

How much more IL1-ra vs. IL-1 does manipulated serum have at 24 hours (i.e. what is the IL1-ra to IL-1 ratio)?

A

6-10x more IL1-ra vs. IL1

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26
Q

How can autologous conditioned serum be used to influence inflammation?

A

It can be aseptically injected back into a joint compartment.

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27
Q

How often are autologous conditioned serum injections repeated?

A

Every 2 weeks for 3-4 treatments

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28
Q

What can be done with leftover IRAP serum?

A

Can be frozen for future use

29
Q

Platelets are most commonly associated with _____ and _____. They are also a rich source of _____.

A

clotting, hemostasis, growth factors

30
Q

What are growth factors?

A

Proteins that stimulate growth, proliferation, healing, or cellular differentiation in cells.

31
Q

What do platelets contain within their cellular architecture?

A

alpha granules

32
Q

What are alpha granules?

A

Storage centers for growth factors

33
Q

What are some examples of sub-types of common growth factors?

A
  1. PDGF (platelet-derived growth factor)
  2. TBF-β (transforming growth factor beta)
  3. VEGF (vascular endothelial growth factor)
  4. IGF-1 (insulin -like growth factor)
  5. EGF (epidermal growth factor)
34
Q

What 3 things do all growth factors have a global role in promoting?

A
  1. Cell migration, proliferation, differentiation
  2. Angiogenesis/neovascularization
  3. Matrix/scaffold synthesis for tissue ingrowth
35
Q

What is platelet-rich plasma?

A

A blood-derived therapy that focuses on enriching the plasma substrate from whole blood with growth factors released from platelets.

36
Q

What are the 2 different methods of preocessing of PRP and which one is more common?

A
  1. Centrifuge based (more common)
  2. Filtration based
37
Q

What are the steps to making PRP?

A
  1. Collect whole blood mixed with an anti-coagulant
  2. Initial centrifugation spin - separates RBC from buffy coat and plasma
  3. Second centrifugation spin - separates platelets from majority of plasma
38
Q

Most PRP kits result in _____ platelets per ml.

A

>1000 x 103

39
Q

What do some PRP kits use to stimulate release of growth factors from alpha granules?

A

Calcium chloride or bovine thrombin

40
Q

How is PRP used in the patient?

A

Injected into the site of injury

41
Q

What can we do with unused PRP?

A

Freeze it and thaw at future use

42
Q

In large animal (equine), PRP is predominantly used for _____.

A

soft tissue injury

43
Q

What are some specific examples of uses for PRP in equines?

A

Tendon or ligament sprain/complete tear of fibers

44
Q

PRP is often injected under _____ guidance.

A

ultrasound

45
Q

What is the predominant use for PRP in dogs?

A

Intra-articular injection in management of osteoarthritis

46
Q

What is the market name for autologous protein solution?

A

Pro-stride

47
Q

What is autologous protein solution?

A

Combo of PRP and ACS

48
Q

The first step in processing APS is identical to _____.

A

PRP

49
Q

What does the 2nd processing step of APS do? What does it do for veterinarians?

A

Upregulates IL1-ra without the need to incubate serum;

Makes APS therapy more “point of care” for vets

50
Q

What are stem cells?

A

Biological cells that differentiate into other types of cells.

51
Q

Stem cells can also divide to produce more of the _____ of stem cell.

A

same type

52
Q

What are the 2 types of stem cells?

A
  1. Embryologic
  2. Adult
53
Q

Adult stem cells act as a _____ in the body, and are located in various _____.

A

repair system, tissues

54
Q

What 3 locations in the body have adult stem cells?

A
  1. Bone marrow
  2. Fat
  3. Blood
55
Q

What are autologous stem cells?

A

Stem cells collected from the same patient to be treated.

56
Q

What are allogenic stem cells?

A

Collected from a donor animal and administered into a recipient patient.

(Donor and recipient are the same species)

57
Q

Concentrate aspirated from bone marrow contains _____ of stem cells within the cellular fraction.

A

<1%

58
Q

What is the significance of BMAC containing <1% of stem cells?

A

There is limited ability to directly aspirate bone marrow and then re-administer the concentrate with true stem cell benefit

59
Q

What can we do with BMAC to ensure a true benefit? How much does this increase the cell content and how long does it take?

A

Send to a lab to be cell cultured; increases SC content up to 15-30 million cells - takes 3-4 weeks

60
Q

From where can we get bone marrow aspirations and what instrument is used?

A

Sternum, tuber coxae, humerus (dogs);

Jamshidi needle under sterile technique and local block

61
Q

What is another name for adipose stem cells?

A

Stromal Vascular Fraction

62
Q

What is the difference between stromal vascular fraction and BMAC?

A

SVF has a significant increase in stem cells compared to equal amounts of BMAC;

BUT amount available for therapy (<1 million) is significantly less than culture expanded bone marrow stem cells (15-30 million)

63
Q

How many stem cells per 50g of tissue are latent in SVF?

A

500-750,000

64
Q

_____ therapy remains the largest perceived benefit of adipose stem cells over bone marrow.

A

Point of care

65
Q

Where is fat harvested for adipose stem cells and how?

A

Base of tail head and inguinal region;

Direct excision through skin incision, liposuction using repetition of needle aspiration

66
Q

Both bone marrow and fat derived stem cells are often utilized as _____ therapy.

A

autologous

67
Q

What is the largest hinderance to using allogenic stem cells?

A

Risk of immune reaction to administered allogenic SCs

68
Q

What are allogenic sources of SCs?

A
  1. Dental pulp
  2. Umbilical
  3. Amniotic
69
Q

What are the common routes of administration for stem cells?

A
  1. IV and intra-arterial via tourniquet and regional limb perfusion
  2. Direct admin into site of injury/lesion (U/S guided)
  3. Intra-articular injection

Intro to Surgery (36 decks)

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