PRP, visco-supplemetation and stem cells

31
PRP, visco-supplementation and stem cells in MSC diseases A.Sadauskas, MD Head of Karoliniskes Day surgery center and Surgical departement LACA conference Arthroscopic joint pathology treatment methods 2016 04 08, Kaunas

Transcript of PRP, visco-supplemetation and stem cells

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

Two in one concept for OA treatment

Andia I, Abate M. Expert Opin Biol Ther. 2014 May; 14(5):635-49

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

www.cellularmatrix.info

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

Thank you for your attentionAčiū už dėmesį

Grazie per l‘attenzione