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PRP, visco-supplementation andstem cells in MSC diseasesA.Sadauskas, MD
Head of Karoliniskes Day surgery center and Surgical departement
LACA conference Arthroscopic joint pathology treatment methods 2016 04 08, Kaunas
PRP History
Proven role in healing of soft and hard tissues
First introduced in the 1980s for the treatment of cutaneous ulcers. (Margolis et al, Diabetes Care 2001)
Use expanded in the 1990s in the maxillofacial and plasticsurgery fields. (Marx, J Oral Maxillofac Surg 2004)
Its use in orthopedic surgery began roughly a decade ago– Initially used with bone grafts to augment spinal fusion and
fracture healing
Mechanism of action comprises anti-inflammatory activity and activation of cell-signalling cascades (Barry 2001, Sevens 2004)
PRP Definition
Platelet-Rich Plasma
Is defined as autologous blood fraction with platelet concentration exceeding original blood concentration (200.000 platelets/µL) by 2-6 times
Mazzucco L et al. Vox Sang. 2009; 97(2): 110-118Arnoczky et al, JAAOS 2010
Platelet activation
Resting platelets Activated platelets
http://orthoregensr.com/regenerative-medicine-scien.html
Platelet activation (2)
PRIME. GROWTH FACTORS IN ANTI-AGEING, REGENERATIVE, AND AESTHETIC MEDICINE. DANIEL L. SISTER / MAY 14, 2015
Healing processes in case of injury
− 70% within 10 minutes, almost 100% within 1 hour− Platelets continue the excretion of small amounts of GF within next 7-10 days
http://orthoregensr.com/regenerative-medicine-scien.html
Platelet degranulation takes place mainly during I inflammation phase
Growth factors (found in α granules) facilitatescartilage and synovium regeneration
Akeda K et al. Osteoarthritis Cartilage. 2006; Wu W et al. J Oral Maxillofac Surg. 2007Saito M et al. Clin Exp Rheumatol. 2009
PRP application in clinical practice
Tendinosis, tendinopathies (patelar tendinosis, Achiles tendinopathy)
Enthesopathies (epicondylitis, plantar fasciitis)
Ligamentous injury (ACL reconstrcution surgery)
Cartilage injuryOsteoarthritisOsteochondritis dissecansAvascular femoral head necrosisMuscle injuriesBone augmentation (fusion, non-unions)
Chronic non-healing wounds
Pain scores change after PRP (time-dependent effect)vs. treatment for control patients
I. Andia et al. Br Med Bull 2014; 110:99-115
Forest plot of WMD showing time-dependent effect on pain scores in entesopathies treatment
PRP improves RTP/RTS (return to play/sport) time for elite athletes by 6 days*
…can get you back to what you love to do
*Laver L. et al. Knee Surg Sports Traumatol Arthrosc. 2015 Nov; 23(11):3383-92*
Evidence of PRP benefitin the treatment of osteoarthritis
Greater effect in younger patients (<60 years old)
Better pain reduction in grade I-II osteoarthritis
G. Filardo, E. Kon, A. Roffi, B. Di Matteo, M. L. Merli, M. MarcacciPlatelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration
Knee Surg Sports Traumatol Arthrosc 2015; 23:2459–2474
Effect of repeated PRP injections for early OA (Kellgren-Lawrence I-II)
KOOS pain score and sports activities improvement
Gobbi A et al. Knee Surg Sports Traumatol Arthrosc. 2015 Aug;23(8):2170-7
Annual repetition of PRP injections extend benefit from 12 to 18 months
PRP benefit in the treatment of symptomatic patients with knee OA (1)
Gobbi A et al. Sports Health: A Multidisciplinary Approach 2012; 4(2):162-72
50 active patients with symptomatic knee OA (Kellgren - Lawrence grade 1-3)
A.Gobbi, et al. PRP Treatment in Symptomatic Patients with Knee OA: Preliminary Results in a Group of Active Patients.
S1a S1b
Tegner scale VAS scale
Significant improvement (p < 0.001) Significant improvement (p < 0.001)
PRP benefit in the treatment of symptomatic patients with knee OA (2)
Gobbi A et al. Sports Health: A Multidisciplinary Approach 2012; 4(2):162-72
PRP benefit in the treatment of symptomatic patients with knee OA (3)
There was no significant difference in improvement between patients with previous cartilage shaving (S1a) or microfracture (S1b) in all evaluated scores
Benefit persists without significant difference in improvement(Mann-Whitney U test)
Gobbi A et al. Sports Health: A Multidisciplinary Approach 2012; 4(2):162-72
Not all PRP created equal
Pure PRP (Anitua’s PRGF, 1999)
PRP + leucocytes (Rizzoli Orthop Inst, Bolognaregenlab)
Platelet-rich fibrin
Platelet-rich fibrin + leucocytes
ACP
Effective cellular therapy requires a scaffold for cell migration, progenitor cells which can be converted into bone or soft tissue, and signal proteins to modulate the repair and regeneration process.
The three essential components that make up the tissue-engineering triad
Daher, R.J. et al. New methods to diagnose and treat cartilage degeneration. Nat. Rev. Rheumatol. 2009; 5, 599-607
2 from 3 essential tissue-engineeringcomponents can be put together
PRP (GF)
Hyaluronic acid (matrix/scaffold)
Cytokine modulation
IL-Ira inhibition
Stem cells
Adipose derived SVF
BMSC
Allogenic stem cells
Search for Chondroprotection and chondrofacilitation. Mandelbaum BR. 2015
Viscosupplementation for knee OA
Provides pain relief and improves mobility with 1-5 i.a. injections of HA
Compensates the decrease of intra-articular HA molecular weight and concentration
Benefits of HA last 6-12 months with up to 75% response rate (25 years of clinical experience)
Network of HA chains constitutes ideal cell-friendly matrix
User-friendly preparation and injection
A- blood samplingB – centrifugation of theblood for 5 min
C – PRP + HA fractionafter centrifugation
D – intraarticular kneeinjection
Suggested rehabilitation protocol following PRP injection
Gobbi A, Bathan L. J Knee Surg. 2009; 22:36-44.
All 3 essential components can be put together (1)
PRP (GF)
Hyaluronic acid injection
Cytokine modulation
IL-Ira inhibition
Stem cells
Adipose derived SVF
BMSC (progenitor cells)
Allogenic stem cells
Bone from bone bank (scaffold)
All 3 essential components can be put together (2)
Capanna R. Proceedings Biobridge Generation Congress, Venice. 2013
BMSC
Bone from the bone bank PRP (GF)
Tissue-engineering triad can complement the stable osteosynthesis
Before… …and after
Failed osteosynthesis before composite bone graft (25 old male patient)**
Bone healing 3 months after composite bone graft and stable osteosynthesis**
*Giannoudis PV, Einhorn TA, Marsh D. Injury. 2007;38 (Suppl. 4):S3-6**Innocenti M. Proceedings Biobridge Generation Congress, Venice/Italy. 2014
Fracture healing: the diamond concept*
Efficacy of autologous stem cell-based therapy anddecompression for osteonecrosis of the femoral head
Daltra GC, et al. Stem Cell Research & Therapy 2015
Anteroposterior X-ray radiograph showing minimally invasive decompression
Coronal T1-weighted MRI scans of the right hip before surgery show osteonecroticlesion in Ficat IIB stage
MRI scan shows delimited marrow region of increased signal intensity (arrow) within the necrotic area,hypointense line around them due to reparative new bone
MRI scan after autologous BMMC implantation showing the channel, decreased bone edema and changes of signal in the superior part of the femur
Preoperative (e) and 60-month postoperative anteroposterior (f) radiographs of the same hip showing the femoral head has maintained the sphericity
Ficat and modified Ficat classificationof AVN scoring
http://radiologykey.com/imaging-of-the-hip-and-pelvis/
A-mildB-moderateC-severe
Lithuanian experience in composite bone grafting in avascular femoral head necrosis
Prof. S.Tarasevičius. LHSU KK, Clinic of orthopedics and traumatology
Vencevičius R., MD. VUH SK, Department of orthopedics & traumatologyJonaitis T., MD. Baltic-American clinic, Vilnius
Fiodorovas M., MD. Klaipeda city university hospital
Prof. Š.Tarasevičius. Nauja galimybė atkurti sunykusį šlaunikaulio galvos kaulą. Lietuvos gydytojo žurnalas. 2015; 10: 66-68
Take home message
PRP regulates cartilage and synovium regeneration by anti-inflammatory action and cell-signaling cascade (GF)
PRP combined with HA creates synergy in reducing inflammation, relieving pain and restoring patient mobility
Tissue engineering triade (PRP/GF, MSC and scaffold) is a potentialtreatment option in complicated cases of non-union in addition to stable osteosynthesis
Autologous stem cell-based therapy with decompression is a promissing treatment option for osteonecrosis of the femoral head
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