the future of prp and stem cells in sports medicine · the future of prp and stem cells in sports...
Post on 09-Feb-2020
0 Views
Preview:
TRANSCRIPT
11/21/2017
1
The Future of PRP and Stem Cells in Sports Medicine
Drew A. Lansdown, MD
Assistant Professor
Sports Medicine & Shoulder Surgery
University of California, San Francisco
2
11/21/2017
2
11/21/20173
Outline
Platelet-Rich Plasma
• Composition and preparation
• Clinical evidence to support or not support its use
Bone marrow aspirate and adipose-derived stem cells
• Preparation and differences
• Clinical evidence to support/not support its use
Discuss how to talk about these treatments with patients
11/21/2017
3
What Is Platelet-Rich Plasma?
Volume of plasma with platelet count above baseline of whole blood
Various growth factors are present in alpha granules of platelets
Concentration of these growth factors may be a powerful directed biologic treatment
Role of Various Growth Factors
11/21/2017
4
Not All PRP Is The Same! Type of Platelet Rich Plasma Presence of
Leukocytes?
Fibrin
Architecture
Pure platelet-rich plasma
(P-PRP)
No Low-density
Leukocyte- and platelet-rich
plasms (L-PRP)
Yes Low-density
Pure platelet-rich fibrin
(P-PRF)
No High-density
Leukocyte- and platelet-rich
plasma (L-PRF)
Yes High-density
Caption™ Smith & Nephew
Cascade™ MTFSymphony II™ DePuy
Magellan™ Medtronic GPS®III Biomet
Arthrex ACP™
Patient Factors Contribute To PRP Composition
High-fat meal increases peripheral platelet counts in healthy volunteers compared to fasting (ref 14)
Platelet aggregation in the morning is higher than later in the day (ref 15)
Platelet concentrations increase in the afternoon and activation decreases from noon to midnight (ref 16)
11/21/2017
5
Preparing PRP
Peripheral Blood Draw• Use at least 21 gauge needle• Performed slowly to prevent
premature activation• Use polypropylene tubes
Platelets Separated by Centrifugation
• Initial spin at 1200-1500 RPM• Separates platelets, WBC, RBCs• Second optional spin at
4000-7000 RPM to further concentrate platelets into same layer as WBCs
#1 #2
Final PRP is Ready for Injection
#3
Activating PRP
Advantage of exogenous activation – growth factors are immediately available (ref 36)
• Clot can then be implanted directly at desired location
• Useful in the surgical application of PRP
• Can use bovine thrombin (ref 37) or autologous thrombin (38)
• Calcium chloride can be exogenous activator (ref 8, 41) but has low pH so may be more painful (ref 8)
• Activation gives immediate release, while endogenous activation has release over longer period of time
No additives
• pH-based variation in platelet function
• Ref 46 – platelet function is effected by incubation with lidocaine, bupivicaine, and tocainide
• Recommend injecting without local anesthetic
11/21/2017
6
Frequency of Injection
Variable literature on multiple vs single injection
Most studies lack a comparison of multi vs single injections so hard to isolate this as a variable
Platelet-Rich Plasma:Usage in Practice
Zhang, et al. OJSM, 2016.
Usage of PRP is increasing in clinical setting
Per-patient average charges reported at $1755 (Zhang)
Cost for patient ranges from $500-$1500 per injection (Samuelson, Arthroscopy, 2016)
11/21/2017
7
What Are The Results For PRP In Practice?
Tendinopathies
• Lateral epicondylitis
• Patellar tendinitis
• Achilles tendinitis
• Rotator cuff tendinopathy/partial rotator cuff tears
Ligament injuries
Muscle injuries
Osteoarthritis
PRP For Tendinopathy
11/21/2017
8
20 patients with elbow tendinosis, failed prior treatment:
• 15 patients treated with LR-PRP
• 5 control patients received bupivicaine injection
Symptom duration
• 15 months in PRP group
• 11 months in control group
RCT of LR-PRP vs corticosteroid for chronic lateral epicondylitis
• 51 patients in LR-PRP group
• 49 patients in corticosteroid group
Persistent symptom relief and improved function in PRP group out to 2 years
11/21/2017
9
RCT for chronic lateral epicondylitis with symptoms for at least 3 months:
• 116 in PRP, leukocyte-enriched
• 114 in active control
12-week no difference
24-week significant improvement in pain and reduced tenderness
11/21/201718
Conclusions:“Platelet-rich plasma is a safe and promising therapy in the treatment of recalcitrant PT. However, its superiority over other treatments such as physical therapy remains unproven.”
11/21/2017
10
11/21/201719
83 patientsProspective study6 month follow up
No ruptures, 10% failure rate requiring repeat injectionConcluded single LR PRP injection safe and effective
11/21/201720
placebo.
PRP injection did not result in an improved VISA-A score over a 3-month period in patients with chronic AT compared with placebo.
Randomized control trial with 24 total patients
• 12 in PRP group
• 12 in saline group
13 patients discontinued study after 3 months due to unsatisfactory results
• 9/12 in PRP group, 4/12 in saline group
11/21/2017
11
11/21/201721
Randomized Controlled Trials—Achilles Tendinopathy
Authors Year Journal N Findings
De Vos 2010 JAMA 54 No difference in saline vs PRP when added to eccentric exercises
De Jonge 2011 AJSM 54 No difference in outcomes between placebo and PRP injection
Kearney 2013 BJR 20 No difference in outcomes between placebo and PRP injection when added to eccentric exercises
TAKEAWAY POINT: PRP not harmful in the treatment of Achilles tendinopathyMinimal clinical benefit proven at this point in time.
What about PRP for tendinopathy/PTRCT?
Randomized patients with partial tears to steroid vs PRP injection
Both groups got betterPRP slightly better than steroid at 12 weeksNo difference at 6 monthsNo difference in MRI findings at 6 months
11/21/2017
12
wA
Slight improvement with PRPAt 3 months, no difference at 6 months
What about PRP for tendinopathy/PTRCT?
ANo difference between exerciseAnd PRP injections at 1 year
What about PRP for tendinopathy/PTRCT?
11/21/2017
13
18 studies including 1066 patients with tennis elbow, rotator cuff tendinitis, and Achilles tendinopathy
Greatest effect seen with leukocyte-rich PRP
Standardized mean differences in pain scores:
• LR-PRP: 36.38
• LP-PRP: 26.77
• Controls: 14.6-25.2
PRP For Muscle Injuries
11/21/2017
14
Meta-analysis of 5 level 1 or 2 comparative studies
Grade 1 or 2 muscle strains (primarily hamstring)
Heterogeneous with regards to PRP formulation and dosing regimens
Re-injury rate of 14.3% (PRP) vs 17.1% (control)
PRP For Ligament Injuries
11/21/2017
15
Ulnar Collateral Ligament Injuries
34 high-level throwing athletes with partial UCL tears
Single type 1A PRP injection under ultrasound
88% returned to same level of play
Average return to play was 12 weeks
One subject underwent UCL reconstruction
High-Ankle Sprains 16 athletes randomized to two injections of LP-PRP activated with calcium chloride
Control group received rehab program
11/21/2017
16
PRP For Osteoarthritis
11/21/201732
AJSM 2017
11/21/2017
17
11/21/201733
AJSM 2017
W
L
Worked better for mild OA, lower BMI
Lowers pro-inflammatory cytokines.
Conclusion: “significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA.”
11/21/201734
Systematic Reviews of Level 1 and Level 2 evidence
Riboh et al AJSM 2015Campbell et al Arthrosc 2015
Khoshbin et al Arthrosc 2013Chang et al APMR 2014
Studies favor PRP with modest effectNo evaluation of alteration of natural history
11/21/2017
18
11/21/201735
PRP and Early OA
Level 1, 2 evidence
Likely beneficial with LP-PRPResults seem to last for ~1 year
No evidence to support structural regenerationNo long term data on natural history
PRP and Early OA
Level 1, 2 evidence
Likely beneficial with LP-PRPResults seem to last for ~1 year
No evidence to support structural regenerationNo long term data on natural history
Stem Cell Injections
11/21/2017
19
Rationale For Stem Cell Treatment
Mesenchymal stem cells (MSCs) have potential to differentiate into cartilage, bone, tendon, and muscle
May allow for targeted regeneration of tissue
MSCs are present in both bone marrow and adipose tissue
Selected Animal Evidence for Stem Cell UseAuthors Journal Year Findings
Harman, et al Frontiers in Veterinary Science
2016 Allogeneic adipose-derived MSCs showed improvement in functional scores and apparent pain in dogs with OA
Latief, et al Cell Biology International
2016 Treatment of arthritic rat knees with differentiated chondrocytes from adipose-derived stem cells showed cartilage regeneration while no changes noted in control group
Moreno, et al Journal of Nuclear Medicine
2016 Mice with OA treated with human adipose-derived stem cells showed decrease in knee inflammation and cartilage degeneration relative to saline control
Fortier, et al JBJS 2010 Treatment of full-thickness chondral defects with BMAC resulted in significantly better healing of defects compared to microfracture control group
11/21/2017
20
Stem Cell SourcesBone Marrow Aspirate Concentrate (BMAC)
Source Commonly iliac crestOther options proximal tibia, calcaneus, other sources
Harvest Method Bone marrow aspiration needle into anterior or posterior iliac crest
Quantity Extracted 60-120 ml
Mesenchymal Stem Cell Yield 0.01-0.001% of cells (ref 42 from Dragoo)
Stem Cell Sources
Adipose-Derived Stem Cells
Source Commonly intra-abdominalPotentially infrapatellar fat pad
Harvest Method 17 gauge needle to inject 120 ml saline/local anesthetic into abdomen
QuantityExtracted
80-120 ml
MesenchymalStem Cell Yield
Up to 10% of cells (ref 4, 52 from Dragoo)
11/21/2017
21
18 patients with knee OA
Treated with low, medium, or high-dose injection of adipose-derived MSCs
Performed knee arthroscopy/lavage followed by injection of AD-MSCs
No adverse events
11/21/2017
22
Limited level 3 and level 4 studies
Treatment appears safe but no data available to recommend dosing, aspirate amount, or efficacy
Limitations of Studies
Many reports have no control group
Inconsistent reporting of exact formulation of biologic
When interpreting these studies, pay attention to:
• Injection protocol
• Presence/absence of leukocytes
• Control group comparison
11/21/2017
23
Discussing These Treatments With Patients
Will PRP/stem cell injections re-grow cartilage?
Will this regenerate my meniscus?
Can this keep me from getting a knee/hip/shoulder replacement?
NO!
Discussing These Treatments With Patients
How does it work then?
• Likely pain relief through anti-inflammatory mediators
• Unlikely to change structure
What about the cost?
• Most treatments are out-of-pocket and expensive
• Limited duration of relief with most treatments
• Consider participating in clinical trials when possible
11/21/2017
24
My Recommendations Recommend LR-PRP for:
• Lateral epicondylitis with >3 months of symptoms
Consider PRP for:
• Elite-level athlete with high-ankle sprain, partial UCL tear, or grade 1-2 muscle strain
• Early osteoarthritis (KL grades 1-2) if non-responsive to cortisone/HA injections
No data to currently support:
• PRP for patellar tendinitis, Achilles tendinitis, and rotator cuff tendinopathy
Need further studies on BMAC/AD-MSC injections
Conclusions
Platelet-rich plasma and stem cell injections hold promise as potential treatment options for various musculoskeletal conditions
Not all formulations are the same
High level, controlled trials are needed before widespread recommendation of these methods
11/21/2017
25
Questions?
top related