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Cell Therapy in Orthopedic and Cartilage
Healing - New Frontiers
Rogerio Teixeira da Silva, MD. PhD
Chairman - NEO Orthopedic Sports Medicine
Samaritano Hospital - São Paulo, Brazil
Director - Brazilian Orthopedic Society for Sports Medicine
Toronto, May 14th 2013
www.neo.org.br
http://docroger.blogspot.com
The Biological Era
PLATELET RICH PLASMA / STEM CELL / TISSUE ENGINEERING
Cartilage Healing Example
1. Good environment
Scaffold / Clot
2. Good stem cell
Chondroblasts
3. Growth factors
PDGF, TGF beta
THE NEEDS FOR SUCCESSFUL TREATMENT
Case Report - Pro Tennis
Knee Injury
23 yo, female, rk 1 in Brazil, rk 150 WTA in 2010
Partial lateral meniscectomy 7 months before
Pain + swelling after practice
Didn’t return to competitions after the prior surgery
Physical exam: effusion + pain at the lateral side
MRI - Chondral damage LFC grade 3-4
O QuickTime™ e um
xvid descompressor
são necessários para ver esta imagem.
Case Report - Pro Tennis
Knee Injury
Drilling + PRP
O QuickTime™ e um
xvid descompressor
são necessários para ver esta imagem.
O QuickTime™ e um
xvid descompressor
são necessários para ver esta imagem.
Drilling + PRP
O QuickTime™ e um
xvid descompressor
são necessários para ver esta imagem.
Drilling + PRP
Aquiles Tendinopathy
PRP therapy for chronic tendon pathology for the aquiles tendon
Clinical Evidence
PRP not better than placebo
Achilles tendinopaty with NO rupture (LE 1, PRCT)
2 groups (27 pts each) - ONLY tendon thickening
PRP (GPS II, Biomet®) vs Saline / Eccentric Training)
OBS: EXCLUDED PARTIAL RUPTURES
Clinical Evidence
Partial Rupture - Aquiles (2011) - level 4
Clinical case
MC, 42 YO, AMATEUR TENNIS
RUPTURE - ACUTE
Male, 45 yo - Jan 2011
August 2011(7 months) Courtesy: JL Runco
Soccer, male, 47 yo - October 2006 - complete rupture
January 2007
(3 months)
Courtesy: JL Runco
Tennis elbow
PRP therapy for chronic tendon pathology around the elbow joint
Clinical Case 1 (amateur)
FMC, 44 yo, male, elbow pain 8 mponths (PT +
SWT without resolution of the pain)
Proposed treatment - US guided PRP injection (2ml)
/ non activated / tendon dry needling
4 WEEKS POS PRP
NO SYMPTONS
Clinical Case 1 (amateur)
RTP AFTER
6 WEEKS
2 year follow-up MRI
A - MRI before treatment
(coronal, T2 fat)
B - 2 year FU MRI
(coronal, T2 fat)
RCCA, 66 yo, male, tennis player (8hs/week), pain at the R
elbow during the last 2 years (PT 65 sections / acupunture)
Partial rupture 1,2cm (ERC tendon)
Clinical Case 2 (amateur)
5 WEEKS - PAIN VAS = 2
PRP injection (2.5ml) guided by US
PT after 5 days
Clinical Case 2 (amateur)
Rotator Cuff
Use of PRP injection for the treatment of RC patology (partial
tears (articular) / tendinopathy
Clinical case - RC partial
tear
RBF, 65 yo, male, amateur tennis player, R shoulder pain last
3 years (PT / acupunture / 2 CE infiltration)
Partial tear 1,0cm (PASTA)
Infiltration of 2.5ml of PRP - non activated
O QuickTime™ e um
DVCPRO50 - NTSC descompressor
são necessários para ver esta imagem.
Clinical case - RC partial
tear
Pain (moderate) during the first 3 days (analgesic drug for this
period)
Pain decreased progressively
2 weeks FU: it is possible to sleep without pain
6 WEEKS - POST
NO PAIN
US showing no doppler active sites with healing
Clinical case - RC partial
tear
Caso Clínico - MR
(amador)
6 WEEKS - POST
NO PAIN
Muscle rupture
PRP treatment for partial and complete muscle ruptures
Clinical Case - Tennis leg
FF, 44yo, male, business man, amateur tennis player
Pain at the R calf when running to the net (4 hours ago)
Muscle rupture (g.3) medial gastroc. (5 cm)
D D E D E
PRP injection guided by US (48 hours after the injury)
6ml (total)
O QuickTime™ e um
Microsoft Video 1 descompressor
são necessários para ver esta imagem.
Clinical Case - Tennis leg
Return to tennis = 3 weeks (no pain 1 week after the injection)
FU (2 years and 6 months) = normal
US (CONTROL) = 4 WEEKS
Clinical Case - Tennis leg
Knee Osteoarthitis
PRP treatment for mild to moderate OA of the knee
Evidence - Level 2
Spakova et al, Am J Phys Med Rehabil 2012; 91: 411-17
Conclusions: Our preliminary findings support the application of
autologous PRP as an effective and safe method in the treatment of the
initial stages of knee osteoarthritis. Further studies are needed to
confirm these results and to investigate the persistence of the
beneficial effects observed
Level of Evidence: Level II, cohort prospective study
120 patients / HA vs PRP (up to 6 months follow-up)
Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A:́ ́
Treatment of knee joint osteoarthritis with autologous platelet-rich
plasma in comparison with hyaluronic acid.
Am J Phys Med Rehabil 2012; 91:411-417.
Evidence - Level 1
Sanchez et al, Arthroscopy 2012; 28(8): 1070-78
Conclusions: Plasma rich in growth factors showed superior short-
term results when compared with HA in a randomized controlled trial,
with a comparable safety profile, in alleviating symptoms of mild to
moderate osteoarthritis of the knee.
Level of Evidence: Level I, randomized controlled multi-center trial
176 patients / RCT HA vs PRP (up to 24 weeks of follow-up)
Evidence - Level 1
Sanchez et al, Arthroscopy 2012; 28(8): 1070-78
Personal Experience
5 years - 365 cases (in protocols - RC, Achilles, Elbow, Patella, Muscle,
Chondral injury - knee)
- more than 6 months of pain, chronic, more than 2 treatments without
success, indication for surgery
* Tennis elbow paper: 78 cases - minimum FU of 1 year (clinical)
- 75,6% of the patients (59) return to play tennis (same level)
- average = RTP after 8 weeks and 3 days (5 to 16 weeks)
- Failure:
*Surgery on 8 patients (10,25%)
* Lost to FU or stop to play tennis = 11 (14,15%)
Adult Mesenquimal Stem
Cell
New treatment, with old concepts = restore cartilage cells
- fat = a good source for harvesting the stem cell
- Lipoaspirate samples = perfect for culture (protocol = Baptista et al, 2009)
Adipose Mesenquimal Stem
Cell
New treatment, with old concepts = restore cartilage cells
- fat = a good source for harvesting the stem cell
- Lipoaspirate samples = perfect for culture (protocol = Baptista et al, 2009)
Stem Cell - Tendons
Carvalho AM et al, 2011
Protocol - Chondral Injury
(Knee)
Example of a grade III medial femural condyle chondral injury
- Arthroscopy + microfracture
- Harvesting - 150ml lipoaspirate (abdominal region)
- Sent to the lab for culture (air transportation)
- 4 to 6 weeks: cells are good for implantation
- Injection of 2 x 106
cells / 3 applications / 2 weeks intervals
Protocol - Harvesting Kit
FAT RECIPIENT
(FOR STEM CELL)
BLOOD TUBES (4)
(FOR PRP / TEST)
Protocol - Lipoaspirate
Protocol - Lipoaspirate
Protocol - Harvesting Kit
Stem Cell Injection + PRP
MISHRA ET AL, 2009
Stem Cell Injection + HA
SAW ET AL, ARTHROSCOPY PREVIEW 2013
Conclusions: After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions,
postoperative intra-articular injections of autologous PBSC in combination with HA resulted in
an improvement of the quality of articular cartilage repair over the same treatment without
PBSC, as shown by histologic and MRI evaluation.
Level of Evidence: Level II, randomized controlled trial (RCT).
50 patients / Chondral injuries of the knee / Drilling + PBSC injections and/or HA
Stem Cell Injection + HA
SAW ET AL, ARTHROSCOPY PREVIEW 2013
18 MONTHS (PO)
The results can be
promising
AT, 57 yo, male, runner (amateur), pain at the R ankle during the last 3 years
- Ankle arthroscopy 2 year ago: didn’t return to run after 1 year PO (still felt
pain for run / walk + swelling)
- THERAPY: Arthroscopy + microfracture + PRP + Stem Cell (patient
consent - initial study for protocol) - Able to run (12 km / week) = 6 months
6 MONTHS
PRP + STEM
CELL
But...we need more
research
Clinical protocols - 9 cases until now
(Chondral injury 6 - knee and ankle / OA 3)
- FU = 6 months
- Good results to control pain
- It seems that the coverage of the cartilage
defect is better (MRI view)
BUT = we need to WAIT to confirm our
HYPOTESIS
To PRP or NOT PRP = that’s the
question
For me it is AN OPTION of TREATMENT
MEDICINE
“The science of transient solutions”...let’s see it in the future
Don’t believe in miracles in your life
PRP in my hands:
- helped me to solve some chronic tennis elbow
- help some patients that didn’t want to operate
(aquiles and elbow tendinopathy)
- help my PT team for pain control during rehab
(rotator cuff tendinopathy)
- stimulated myself to study biology
Rogerio Teixeira da Silva, MD,
PhD
Orthopedic and Sports Medicine
Sao Paulo, Brazil
Sao Paulo, Brazil
Sao Paulo, Brazil
rgtsilva67@me.com
www.neoesporte.com

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Cell Therapy in Orthopedic and Cartilage Healing

  • 1. Cell Therapy in Orthopedic and Cartilage Healing - New Frontiers Rogerio Teixeira da Silva, MD. PhD Chairman - NEO Orthopedic Sports Medicine Samaritano Hospital - São Paulo, Brazil Director - Brazilian Orthopedic Society for Sports Medicine Toronto, May 14th 2013 www.neo.org.br http://docroger.blogspot.com
  • 2. The Biological Era PLATELET RICH PLASMA / STEM CELL / TISSUE ENGINEERING
  • 3. Cartilage Healing Example 1. Good environment Scaffold / Clot 2. Good stem cell Chondroblasts 3. Growth factors PDGF, TGF beta THE NEEDS FOR SUCCESSFUL TREATMENT
  • 4. Case Report - Pro Tennis Knee Injury 23 yo, female, rk 1 in Brazil, rk 150 WTA in 2010 Partial lateral meniscectomy 7 months before Pain + swelling after practice Didn’t return to competitions after the prior surgery Physical exam: effusion + pain at the lateral side MRI - Chondral damage LFC grade 3-4
  • 5. O QuickTime™ e um xvid descompressor são necessários para ver esta imagem. Case Report - Pro Tennis Knee Injury
  • 6. Drilling + PRP O QuickTime™ e um xvid descompressor são necessários para ver esta imagem.
  • 7. O QuickTime™ e um xvid descompressor são necessários para ver esta imagem. Drilling + PRP
  • 8. O QuickTime™ e um xvid descompressor são necessários para ver esta imagem. Drilling + PRP
  • 9. Aquiles Tendinopathy PRP therapy for chronic tendon pathology for the aquiles tendon
  • 10. Clinical Evidence PRP not better than placebo Achilles tendinopaty with NO rupture (LE 1, PRCT) 2 groups (27 pts each) - ONLY tendon thickening PRP (GPS II, Biomet®) vs Saline / Eccentric Training) OBS: EXCLUDED PARTIAL RUPTURES
  • 11. Clinical Evidence Partial Rupture - Aquiles (2011) - level 4
  • 12. Clinical case MC, 42 YO, AMATEUR TENNIS RUPTURE - ACUTE
  • 13. Male, 45 yo - Jan 2011 August 2011(7 months) Courtesy: JL Runco
  • 14. Soccer, male, 47 yo - October 2006 - complete rupture January 2007 (3 months) Courtesy: JL Runco
  • 15. Tennis elbow PRP therapy for chronic tendon pathology around the elbow joint
  • 16. Clinical Case 1 (amateur) FMC, 44 yo, male, elbow pain 8 mponths (PT + SWT without resolution of the pain)
  • 17. Proposed treatment - US guided PRP injection (2ml) / non activated / tendon dry needling 4 WEEKS POS PRP NO SYMPTONS Clinical Case 1 (amateur) RTP AFTER 6 WEEKS
  • 18. 2 year follow-up MRI A - MRI before treatment (coronal, T2 fat) B - 2 year FU MRI (coronal, T2 fat)
  • 19. RCCA, 66 yo, male, tennis player (8hs/week), pain at the R elbow during the last 2 years (PT 65 sections / acupunture) Partial rupture 1,2cm (ERC tendon) Clinical Case 2 (amateur)
  • 20. 5 WEEKS - PAIN VAS = 2 PRP injection (2.5ml) guided by US PT after 5 days Clinical Case 2 (amateur)
  • 21. Rotator Cuff Use of PRP injection for the treatment of RC patology (partial tears (articular) / tendinopathy
  • 22. Clinical case - RC partial tear RBF, 65 yo, male, amateur tennis player, R shoulder pain last 3 years (PT / acupunture / 2 CE infiltration) Partial tear 1,0cm (PASTA)
  • 23. Infiltration of 2.5ml of PRP - non activated O QuickTime™ e um DVCPRO50 - NTSC descompressor são necessários para ver esta imagem. Clinical case - RC partial tear
  • 24. Pain (moderate) during the first 3 days (analgesic drug for this period) Pain decreased progressively 2 weeks FU: it is possible to sleep without pain 6 WEEKS - POST NO PAIN US showing no doppler active sites with healing Clinical case - RC partial tear
  • 25. Caso Clínico - MR (amador) 6 WEEKS - POST NO PAIN
  • 26. Muscle rupture PRP treatment for partial and complete muscle ruptures
  • 27. Clinical Case - Tennis leg FF, 44yo, male, business man, amateur tennis player Pain at the R calf when running to the net (4 hours ago) Muscle rupture (g.3) medial gastroc. (5 cm) D D E D E
  • 28. PRP injection guided by US (48 hours after the injury) 6ml (total) O QuickTime™ e um Microsoft Video 1 descompressor são necessários para ver esta imagem. Clinical Case - Tennis leg
  • 29. Return to tennis = 3 weeks (no pain 1 week after the injection) FU (2 years and 6 months) = normal US (CONTROL) = 4 WEEKS Clinical Case - Tennis leg
  • 30. Knee Osteoarthitis PRP treatment for mild to moderate OA of the knee
  • 31. Evidence - Level 2 Spakova et al, Am J Phys Med Rehabil 2012; 91: 411-17 Conclusions: Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis. Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed Level of Evidence: Level II, cohort prospective study 120 patients / HA vs PRP (up to 6 months follow-up) Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A:́ ́ Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil 2012; 91:411-417.
  • 32. Evidence - Level 1 Sanchez et al, Arthroscopy 2012; 28(8): 1070-78 Conclusions: Plasma rich in growth factors showed superior short- term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level of Evidence: Level I, randomized controlled multi-center trial 176 patients / RCT HA vs PRP (up to 24 weeks of follow-up)
  • 33. Evidence - Level 1 Sanchez et al, Arthroscopy 2012; 28(8): 1070-78
  • 34. Personal Experience 5 years - 365 cases (in protocols - RC, Achilles, Elbow, Patella, Muscle, Chondral injury - knee) - more than 6 months of pain, chronic, more than 2 treatments without success, indication for surgery * Tennis elbow paper: 78 cases - minimum FU of 1 year (clinical) - 75,6% of the patients (59) return to play tennis (same level) - average = RTP after 8 weeks and 3 days (5 to 16 weeks) - Failure: *Surgery on 8 patients (10,25%) * Lost to FU or stop to play tennis = 11 (14,15%)
  • 35. Adult Mesenquimal Stem Cell New treatment, with old concepts = restore cartilage cells - fat = a good source for harvesting the stem cell - Lipoaspirate samples = perfect for culture (protocol = Baptista et al, 2009)
  • 36. Adipose Mesenquimal Stem Cell New treatment, with old concepts = restore cartilage cells - fat = a good source for harvesting the stem cell - Lipoaspirate samples = perfect for culture (protocol = Baptista et al, 2009)
  • 37. Stem Cell - Tendons Carvalho AM et al, 2011
  • 38. Protocol - Chondral Injury (Knee) Example of a grade III medial femural condyle chondral injury - Arthroscopy + microfracture - Harvesting - 150ml lipoaspirate (abdominal region) - Sent to the lab for culture (air transportation) - 4 to 6 weeks: cells are good for implantation - Injection of 2 x 106 cells / 3 applications / 2 weeks intervals
  • 39. Protocol - Harvesting Kit FAT RECIPIENT (FOR STEM CELL) BLOOD TUBES (4) (FOR PRP / TEST)
  • 43. Stem Cell Injection + PRP MISHRA ET AL, 2009
  • 44. Stem Cell Injection + HA SAW ET AL, ARTHROSCOPY PREVIEW 2013 Conclusions: After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions, postoperative intra-articular injections of autologous PBSC in combination with HA resulted in an improvement of the quality of articular cartilage repair over the same treatment without PBSC, as shown by histologic and MRI evaluation. Level of Evidence: Level II, randomized controlled trial (RCT). 50 patients / Chondral injuries of the knee / Drilling + PBSC injections and/or HA
  • 45. Stem Cell Injection + HA SAW ET AL, ARTHROSCOPY PREVIEW 2013 18 MONTHS (PO)
  • 46. The results can be promising AT, 57 yo, male, runner (amateur), pain at the R ankle during the last 3 years - Ankle arthroscopy 2 year ago: didn’t return to run after 1 year PO (still felt pain for run / walk + swelling) - THERAPY: Arthroscopy + microfracture + PRP + Stem Cell (patient consent - initial study for protocol) - Able to run (12 km / week) = 6 months 6 MONTHS PRP + STEM CELL
  • 47. But...we need more research Clinical protocols - 9 cases until now (Chondral injury 6 - knee and ankle / OA 3) - FU = 6 months - Good results to control pain - It seems that the coverage of the cartilage defect is better (MRI view) BUT = we need to WAIT to confirm our HYPOTESIS
  • 48. To PRP or NOT PRP = that’s the question For me it is AN OPTION of TREATMENT MEDICINE “The science of transient solutions”...let’s see it in the future Don’t believe in miracles in your life PRP in my hands: - helped me to solve some chronic tennis elbow - help some patients that didn’t want to operate (aquiles and elbow tendinopathy) - help my PT team for pain control during rehab (rotator cuff tendinopathy) - stimulated myself to study biology
  • 49. Rogerio Teixeira da Silva, MD, PhD Orthopedic and Sports Medicine Sao Paulo, Brazil Sao Paulo, Brazil Sao Paulo, Brazil rgtsilva67@me.com www.neoesporte.com