Ch 4 PRP Flashcards
What is regenerative medicine?
RRR, goals (3)
interdisciplinary field of research and clinical therapy
focused on repair, replacement, or regeneration of cells, tissues, and organs
goals
restoring structure and function to the affected tissue or organ
reduction of inflammation and pain
improved healing of injured tissues
inc stem cell, Gene therapy, PRP
when analysed in the context of RCT, a clear positive effect for platelet-rich plasma becomes less apparent
case series without control groups, involve relatively low sample sizes, are underpowered, and exhibit enrollment bias
what is PRP
how much higher?
plasma fraction of
autologous blood with a concentration of platelets and growth factors/cytokines that is higher than baseline
At least 3-5 times higher
How does PRP act?
proliferation of MSC and fibroblasts
TGF-B > collagen type 1 production in tendons
Platelet role
promote (6)
hemostasis and wound healing
alpha granules > growth factors and cytokines
promote:
1.cell recruitment
2. cell migration,
3. cell proliferation,
4. angiogenesis
5. osteogenesis
6. recruit, stimulate, and provide a scaffold for stem cells
what cytokines and GF platelets have? (9)
platelet-derived growth factor (PDGF)
transforming growth factor (TGF-a), (TGF-b)
vascular endothelial growth factor (VEGF),
fibroblastic growth factor (bFGF),
epidermal growth factor (EGF)
connective tissue growth factor (CTGF),
insulin-like growth factor (IGF),
hepatocyte growth factor (HGF),
keratinocyte growth factor
(KGF)
what does PDGF do?
Mitogenic for mesenchymal cells and osteoblasts.
Stimulates chemotaxis pf WBC and fibroblasts
TGF-a, TGF-b
Stimulates undifferentiated mesenchymal cell proliferation.
Regulates endothelial, fibroblastic, and osteoblastic mitogenesis
Regulates collagen synthesis and collagenase secretion
TNF
Regulates monocyte migration, fibroblast proliferation,
macrophage activation
angiogenesis.
VEGF
Stimulates angiogenesis and mitogenesis for endothelial cells
FGF
Promotes growth and differentiation of chondrocytes and osteoblasts.
Mitogenic for mesenchymal cells,
IGF - 1
Chemotactic for fibroblasts and promotes protein synthesis
What else does PRP contain?PRP for wound healing
Clotting factors
Plasma proteins
antibacterial and fungicidal effects
membrane glycoproteins (influence inflammation)
800 unique proteins
Depending on prep > leukocyte- and platelet-rich plasma (L-PRP)
reasons fo variability in product? (6)
Individual donor variability
concurrent drug therapy
coagulation state
venipuncture technique
processing and isolation method
degree of platelet activation
studies have demonstrated marked variability
major challenge for PRP therapy
Carr 2016
Canine platelet-rich plasma systems: a prospective analysis.
Front Vet Sci.
Franklin 2015
Characteristics of canine platelet-rich plasma prepared with five commercially available systems.
Am J Vet Res.
OA
recent studies > PRP seems to be beneficial in dogs with OA
alpha granules > modulate inflammation and promote tissue healing
treated with a single injection of
PRP may have improvement in validated client survey results and subjective pain
and gait scores as well as objective kinetic gait
ihibit nuclear factor κB and decrease expression of cyclooxygenase-2, which are both important mediators of the inflammatory component of osteoarthritis.
wound healing
4 functions
people and dogs
promotes wound epithelialization,
reduces scar formation,
exhibits antimicrobial activity,
stimulates angiogenesis
moderate (2–3x) and high (4–6x) platelet concentrations are
beneficial for soft tissue and bone healing
still no consensus on the ideal platelet concentration for specific applications.
Multiple studies have investigated the compositional differences of commercially available
PRP systems, but there is still no overall consensus on optimal component
concentrations
Franklin 2015
Characteristics of canine platelet-rich plasma prepared with five commercially available systems. Am J Vet Res
crucial to deliver PRP directly to the site of tissue injury for it to be most effective;
therefore, appropriate intra-articular injection technique and ultrasound-guided soft
tissue injection techniques are crucial for success
Venator 2020 (12 dogs, clinical)
Assessment of a Single Intra-Articular
Stifle Injection of Pure Platelet Rich Plasma on Symmetry Indices in Dogs with Unilateral or Bilateral Stifle Osteoarthritis from Long-Term Medically Managed CCL Disease. Vet Med (Auckl)
Ho 2015
Single ultrasound-guided platelet-rich
plasma injection for treatment of supraspinatus tendinopathy in dogs. Can Vet J
Alves 2021
dogs with moderate and severe osteoarthritis
that were treated with 2 intra-articular injections of PRP 14 days apart found that
the PRP group had significantly better clinical metrology instruments than saline control
group at multiple time points, some up to 180 days
CCL
venator 2020
CCL injury and have also
shown that PRP has beneficial effects in improving pain, lameness, effusion, and/or
overall inflammation within the stifle
6 dogs > ACP-treated knees showed evidence of ACL repair and less severe synovitis.
experimental and clinical studies
soft tissue injury
still limited evidence available
Tendons and ligaments > poor self-repair capability.
Histologic > tendinosis is not an acute inflammatory condition, failure of normal tendon repair mechanism
shown to have a beneficial immunomodulatory effect on tenocytes to stimulate
the secretion of angiogenic proteins in injured tenocytes
Ho 2015
canine study showed that dogs with supraspinatus
tendinopathy treated with a single PRP ultrasound-guided injection had subjective
improvement in lameness and function in 40% of dogs with improved tendon fiber
pattern and in 60% of dogs with improved tendon echogenicity 6 weeks following
treatment.46
How is PRP osteopromotive?
Chondropromotive?
augment bone grafts
Stimulates the production of osteoclast-like cells
Platelets contain a number of grwoth factors to initiate bone healing - PDGF, TGF-B, VEGF, BMP
Chondro:
- Significant increased in chondrocyte proliferation and celular accumulation of GAGs and collagen tpe 2 in porcine chondrocytes with platelet lysate
List 2 contraindications of PRP treatment
Thrombocytopaenia
Coagulation defects
in the human
literature it has been proposed that platelet concentration greater than 6x baseline
(or >1800 x 103 platelets/m) may be detrimental and lead to cellular apoptosis
Most recent studies agree that it is best to reduce RBC in PRP as they have been
shown to have a deleterious inflammatory effect.
limitations (3)
Deficits in basic science research,
inherent variability in “product” due to discrepancies between donors and preparation systems
inability to completely assess individual platelet-rich plasma samples prior to clinical application
soft tissue and bone repair is a temporally complex series of interactions between the injured tissue composed of a diverse population of cells and a dynamic extracellular matrix, recruited leukocytes, and an untold number of growth factors and cytokines.
As such, the ideal platelet number, growth factor concentration, and proper delivery timeline necessary to successfully treat specific diseases remain unknown
ome studies report outcomes after single injections of platelet-rich plasma,25,67,74,92 whereas others have utilized a series of platelet-rich plasma injections.87 Due to differences in preparation systems and dosing regimens, it is difficult to collectively make comparisons and draw conclusions regarding the ideal dosing schedule from these studies.
