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STEFANO ZANASI VILLA ERBOSA HOSPITAL GRUPPO SAN DONATO ORTHOPAEDICS DEPARTMENT IIIRD DIVISION – JOINT ARTHROPLASTY OPERATIVE CENTER CHIEF: STEFANO ZANASI.

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Presentazione sul tema: "STEFANO ZANASI VILLA ERBOSA HOSPITAL GRUPPO SAN DONATO ORTHOPAEDICS DEPARTMENT IIIRD DIVISION – JOINT ARTHROPLASTY OPERATIVE CENTER CHIEF: STEFANO ZANASI."— Transcript della presentazione:

1 STEFANO ZANASI VILLA ERBOSA HOSPITAL GRUPPO SAN DONATO ORTHOPAEDICS DEPARTMENT IIIRD DIVISION – JOINT ARTHROPLASTY OPERATIVE CENTER CHIEF: STEFANO ZANASI M.D.

2 Ther’s high incidence of cartilage injuries in sport sports at greatest risk are linked to sudden direction changes with knee or ankle sprain Football/soccer Rugby Volleyball Basket Ski tennis Cartilage injury is due to - single trauma (sprain) or to - overuse for repetitive microtraumatism in athletic gesture

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4 Costituiscono una popolazione residente nel midollo osseo di cellule adulte non differenziate capace di autorigenerarsi e differenziarsi in cellule del tessuto adiposo, del tessuto cartilagineo, del tessuto osseo e nello stroma che supporta l’ematopoiesi

5 Si ottengono in soli 15 minuti partendo da midollo osseo aspirato da cresta iliaca (60 o 120 ml) attraverso ciclo di centrifugazione operato da una centrifuga di piccole dimensioni, da usare in sala operatoria senza necessità di personale specializzato.

6 La procedura elimina i globuli rossi e il prodotto finale contiene Cellule staminali emopoietiche Cellule staminali mesenchimali Progenitori vascolari Cellule immunitarie e piastrine Fattori di crescita (attivazione con trombina autologa) in un volume finale di 10 o 20 ml La procedura di concentrazione richiede l’utilizzo della centrifuga e del kit BMAC composto di due confezioni (A) contiene il materiale utilizzato nel campo operatorio sterile per il prelievo del midollo da paziente (B) contiene il materiale per la procedura di concentrazione dell’aspirato midollare A B

7 Procedura nella fase 1, si procede al prelievo del midollo da paziente, che viene raccolto in una apposita sacca di sangue e infine trasferito in una siringa per essere passato all’esterno del campo sterile nella fase 2, il campione di midollo viene immesso nella provetta, centrifugato, concentrato nel volume desiderato e di nuovo trasferito al campo operatorio per il definitivo utilizzo mediante connessione di 2 siringhe diverse

8 Sono stati inclusi in questo studio 40 pazienti sportivi di medio-alto livello Affetti da lesione a stampo (>3 <9cm2)), III-IV stadio di Outerbridge interessanti CFM,CFL,rotula Trattati dal 2/2009 al 2/2012 con impianto one step di MSCs da aspirato midollare L ’ et à media è stata di 32a (+/-9a). Tutti i pazienti sono stati ricontrollati ad follow-up medio di 18mesi (8-36ms). La valutazione clinica è stata effettuata utilizzando il La valutazione clinica è stata effettuata utilizzando il protocollo ICRS-IKDC ; la valutazione dell ’ impianto cartilagineo è stato effettuata con RMN ad 1.5T applicando il la valutazione dell ’ impianto cartilagineo è stato effettuata con RMN ad 1.5T applicando il MOCART scoring system. L ’ EuroQol EQ-5D L ’ EuroQol EQ-5D è stato utilizzato per valutare la la qualit à della vita dei pazienti. è stato utilizzato per valutare la la qualit à della vita dei pazienti.

9 Exemplificative case MSCs: PATELLA simple Defect: coin lesion Location: centro- medial area of LEFT/RIGHT patella Size: 1.5 x 2.5 cm Patient: C. V., male, 28 ys. football player Symptoms: Severe pain, locking, giving-way, recurrent effusion History:bilateral ACL reconstruction on summer of 2009 grafted CONCURRENTLY BILATERALLY on 21/06/2009, 2 nd look arthroscopy at 12 ms.

10 C.V., male, 28 years old - grafted on 11/04/2009

11 C.V., male, 28 years old –grafted on 11/04/2009 : DX

12 C.V., male, 28 years old - grafted on 11/04/2009 : SN

13 Patient: C.V. Male, 28 years old Arthroscopy Time: 12 months Follow-up time: 12 months IKDC Subjective Evaluation Score: 95.5 (improvement from baseline: 49.0) Knee functional grade: Normal ICRS Cartilage repair assessment: 12 C.V., male, 28 years old - grafted on 11/04/2009 2nd look at 12ms.f.up

14 C.V., male, 28 years old - grafted on 11/04/2009 2nd look at 12ms.f.up RMN AT 12 MS

15 C.V., male, 28 years old - grafted on 11/04/2009 2nd look at 12ms.f.up - HYSTOLOGY LIGHT STAINING FOR GAGS LOW CONTENT AND NOT-UNIFORM DISTRIBUTION OF TYPE II COLLAGEN PRESENCE OF TYPE I COLLAGEN, NOT CELL CLUSTERING AND COLUMNAR ORGANIZATION DEMONSTRATES THE MATURATION OF IMPLANTED MSCS TO A CLEAR FIBRO-HYALINE-LIKE PHENOTYPE TO A CLEAR FIBRO-HYALINE-LIKE PHENOTYPE WITHOUT PECULIAR CELL ORGANIZATION

16 Exemplificative case: MFC simple C.D, male, 18 years old - grafted on 19/01/2002 Defect: coin lesion Location: medial femoral condyle Size: 2 x 2.5 cm Patient: C.D., male, 21 years old. A1 male Serie football athlete Juvenile National Italian football team History:grafted on 19/01/2002, NMR at 3, 6 and 9, 12, 24 months post op arthroscopic 2nd look on 12/01/2003 **

17 ARTHROSCOPIC ACI TECHNIQUE DEVELOPED BY M. MARCACCI C.D, male, 18 years old - grafted on 19/01/2002

18 2nd look artroscopy at 18 ms f.up 19/01/2002 Follow-up time: 18 months Subjective Evaluation Score: 97.5 (improvement from baseline: 49.0 Knee functional grade:Normal Cartilage repair assessment:12

19 In collaboration with: Prof. A. HOLLANDER, University of Bristol. WELL-MATURED NEOCARTILAGE, WITH STRONG GLICOSAMINOGLYCANS DEPOSITION. STRONG COLLAGEN TYPE II DEPOSITION COLUMNAR CHONDROCYTE REARRANGEMENT INSIDE THE GRAFTED TISSUE C.D, male, 18 years old - grafted on 19/01/2002 2nd look artroscopy at 18 ms f.up C.D, male, 18 years old - grafted on 19/01/2002 2nd look artroscopy at 18 ms f.up

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21 EuroQol (EQ-5D) (N=25 ACT VS 25 MSCs) Statistically significant improvement similar for both groups (pain reduction) (Wilcoxon signed rank test: p<0.0001) Statistically significant improvement in mobility similar for both groups (Wilcoxon signed rank test: p<0.0001) (Wilcoxon signed rank test: p<0.0001) * Roset M et al. Sample size calculations in studies using EuroQol EQ5D. Quality of Life Research 8: , 1999 Pain/discomfort Mobility

22 Normal post-op without serious adverse events correlated to the graft 6/28 cases of increased temperature (<39°) completely ceased within 7 days clinical sympthoms (pain, effusion, catching, giving- way) significantly decreased within the 2nd month, and completely ceased, in all cases, within 3 months WITH GOOD/EXCELLENT JOINT FUNCTIONAL RECOVERY Significative improvement of ROM (flex-ext >15%): average pre-op. active ROM 120° (range 80° - 140°) average post-op active ROM 135° (range 110° - 140°) SATISFACTORY CLINICAL RESULTS at 18 ms. average f. up PRELIMINARY CONCLUSIONS: resurfacing by MSCs

23 Second look arthroscopy at 12 mo.:9/28 Significantly improved appearance of the tissue Total scaffold biodegradation Complete and uniform fibrocartilagineous tissue resurfacing discrete mechanical resistence to probe palpation Areas of uneven cartilage stiffness PRELIMINARY CONCLUSIONS:

24 THE MATURATION THE MATURATION OF IMPLANTED TISSUE ENGINEERED CARTILAGE TO A CLEAR HYALINE-LIKE PHENOTYPE TO A CLEAR HYALINE-LIKE PHENOTYPE WITH PECULIAR CELL ORGANIZATION 2nd look arthroscopy at 12 ms f. up: biopsy DEMONSTRATES HIGH CONTENT AND UNIFORM DISTRIBUTION OF TYPE II COLLAGEN STRONG STAINING FOR GAGS ABSENCE OF TYPE I COLLAGEN, CELL CLUSTERING AND COLUMNAR ORGANIZATION 20x2.5x THE MATURATION THE MATURATION OF IMPLANTED MSCS TO A CLEAR FIBRO-HYALINE-LIKE PHENOTYPE TO A CLEAR FIBRO-HYALINE-LIKE PHENOTYPE WITHOUT PECULIAR CELL ORGANIZATION LIGHT STAINING FOR GAGS LOW CONTENT AND NOT-UNIFORM DISTRIBUTION OF TYPE II COLLAGEN PRESENCE OF TYPE I COLLAGEN, NOT CELL CLUSTERING AND COLUMNAR ORGANIZATION

25 Need to verify the results at 3 and 5 years to appreciate the quality of the reconstructed tissue and the Maintainance/IMPROVEMENT of the (FIBRO)cartilage quality (no degenerative changes?) PRELIMINARY CONCLUSIONS: MSCs RECONSTRUCTION

26 In accordo con quanto scritto in Giannini S., “One-Step Bone Marrow-derived Cell Trasnsplantation in Talar Osteochondral Lesion”, Clin. Orthop. Relat. Res. DOI /s (Associaton of Bone and Joint Surgeons 2009). Questo studio riporta che, in seguito a inoculo del concentrato di midollo osseo su uno scaffold di acido ialuronico esterificato (HYAFF): - non si osserva alcuna complicanza locale nè sistemica - si ha la riformazione di tessuto cartilagineo in modo del tutto sovrapponibile alla consolidata in modo del tutto sovrapponibile alla consolidata tecnica del trapianto di condrociti autologhi. tecnica del trapianto di condrociti autologhi. - in un unico tempo operatorio - in un unico tempo operatorio, senza necessità di prelievo di cartilagine e clonazione della stessa in centro di coltura specializzato con reimpianto successivo dopo circa 30 gg - Significativo minor costo della procedura

27 MSCs cartilage defect 4cm2 Simple wide, ShoulderedComplex-salvage to delay implant arthroplasty Long term Validated results Short term Evaluating results Good functional/clinical results Good (?) % of hyaline tissue duration? Good functional/clinical results Good % of hyaline tissue 14 yrs f.up

28 EXCELLENT INTEGRATION OF THE NEOFORMED TISSUE WITH THE SUBCHONDRAL BONE. THE TYDE-MARK IS DEVELOPING EXCELLENT INTEGRATION OF THE NEOFORMED TISSUE WITH THE SUBCHONDRAL BONE. THE TYDE-MARK IS DEVELOPING C.D, male, 18 years old - grafted on 19/01/2002 2nd look artroscopy at 18 ms f.up

29 MSCs 56 pts. from 02/09 to 02/12 MSCs : 56 pts. from 02/09 to 02/12 for chondral knee defects Outerbridge stage III/IV according to Tom Minas’ classification simple 32/56 simple 32/56 26 sportmen coin defect (troclea, patellar, condyle/s, emi-tibial plate) coin defect (troclea, patellar, condyle/s, emi-tibial plate) complex 11/56 complex 11/56 5 sportmen shouldered massive unipolar defect of the lateral/medial condyle plurifocal not kissed and differently combined/spared coin defects plurifocal not kissed and differently combined/spared coin defects (troclea, patellar, condyle/s, emi-tibial plate) (troclea, patellar, condyle/s, emi-tibial plate) salvage 13/56 salvage 13/56 11 sportmen shouldered, limited kissing lesions not requiring realignment procedure unshouldered kissing lesions and uni-compartmental OA concurrently with unloading/corrective osteotomy concurrently with unloading/corrective osteotomy 32/56 sportmen average age 25 ys (range ) - 47% F average defect size 3.5 cm 2 (range 2.5 – 12.5cm)


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