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Bone and Cartilage regeneration with cells
and tissue engineering products
Enric Càceres
Chair Orthopaedics
Universitat Au...
The role of mesenchymal stem cells
• Management of large bone defects and cartilage
loss continues to be a challenge
• Uri...
The role of mesenchymal stem cells
MSCs Origin
•Bone marrow
•Adipose tissue (including fat pad from knee)
•Periostium
•Syn...
The role of mesenchymal stem cells
The role of mesenchymal stem cells
XCEL-MT-10-02
• Lumbar fusion in degenerative surgery:
Autologous iliac graft  Gold standard
– Local complications
– Limi...
XCEL-MT-10-02
PUBMED:
Mesenchymal stem cells 26129
Mesenchymal stem cells and bone regeneration  2911
Mesenchymal stem c...
XCEL-MT-10-02
Biomaterials. 2008 Oct;29(29):3973-82. doi: 10.1016/j.biomaterials.2008.06.026.
Epub 2008 Jul 18.
The clinic...
XCEL-MT-10-02
Zhonghua Wai Ke Za Zhi. 2008 Apr 1;46(7):493-6.
Clinical study of lumbar fusion by hybrid construct of stem ...
11
Title: "Ex Vivo" Expanded Autologous Bone Marrow
Mesenchymal Stem Cells Fixed in Allogenic
Human Bone Tissue for Spinal...
XCEL-MT-10-02
Design: Phase I/II, prospective, open (blind assessment),
randomized, parallel, only one dose and multicentr...
Experimental study
Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
Experimental study
Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
Experimental study
Focal cryogen insults for inducing
osteonecrosis
Lead By Mario Aguirre and Roberto Vélez,Hospital Valle...
Experimental study
Histology of therapeutic model
Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
Purpose and hypothesis
Purpose
Randomized study, compares the spinal fusion obtained after
instrumentation and the use of ...
18
Sample: 62 Patients, age18-85a, bout sex.
Group A: Surgical fusion using autologous mesenchymal cells
expanded “ex vivo...
• Extracción
Bone marrow aspiration
Bone marrow aspiration
• Extracción
Initial harvest bone marrow
Spread Cell Stack
Microscopically assessment of the sample
celularity and brooding culture
Cul...
Volume Reduction (Spin cycle place the MSCc at the
bottom of the pack)
CellStacks
Strict
conditions
Cèl-lules mesenquimals...
• Extracción
Implant:Implant: TLIF L4-L5
TLIFTLIF
Implant:Implant: TLIF L4-L5
XCEL-MT-OSTEO-ALPHAXCEL-MT-OSTEO-ALPHA
XR AssessmentXR Assessment
independent radiologistindependent radiologist
• Molinari score by independent radiologistMolin...
CT AssessmentCT Assessment
independent radiologistindependent radiologist
• Anterior interbody fusion, facet fusion andAnt...
2014 status of the study2014 status of the study
Centre Selected
(CI signature)
Selection
Failure
Random Random On going
p...
007 patient007 patient
Radiologist report
Posterorolateral multiple graft around rods with
continuous bridges more special...
007007
patientpatient
001 Pacient001 Pacient
BCN Trials
Process to applying MSCs for bone repair
MSCs directly
implanted without ex vivo
expansion
BCN Experience
Non expanded MSCs
• Avoid cost and time
• Depend on the number and concentration
• <1000 cell per cm3
or< 30.000 cells in ...
Future MCSs in Orthopedics
Looks promising as advances in
• Tissue engineering
• Biomaterial
• Cell biology
Converge
• To ...
Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015
Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015
Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015
Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015
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Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015

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Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015 http://www.bdebate.org/en/forum/advanced-therapies-and-regenerative-medicine-promise-21st-century

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Bone and Cartilage regeneration with cells and tissue engineering products - Dr. Enric Cáceres - B-Debate 17/02/2015

  1. 1. Bone and Cartilage regeneration with cells and tissue engineering products Enric Càceres Chair Orthopaedics Universitat Autònoma de Barcelona
  2. 2. The role of mesenchymal stem cells • Management of large bone defects and cartilage loss continues to be a challenge • Urist 1970 discovers Bone Morphogenetic Protein • Autologous or allogeneic MSCs can be expanded and then may be loaded in the variety of scaffolds
  3. 3. The role of mesenchymal stem cells MSCs Origin •Bone marrow •Adipose tissue (including fat pad from knee) •Periostium •Synovium •Artery walls
  4. 4. The role of mesenchymal stem cells
  5. 5. The role of mesenchymal stem cells
  6. 6. XCEL-MT-10-02 • Lumbar fusion in degenerative surgery: Autologous iliac graft  Gold standard – Local complications – Limited amount of material No union 5-35% (depending condition) • Alternatives: • BMP • Mesenchyme Stem Cells
  7. 7. XCEL-MT-10-02 PUBMED: Mesenchymal stem cells 26129 Mesenchymal stem cells and bone regeneration  2911 Mesenchymal stem cells and spinal fusion  86 Mesenchymal stem cells and spinal fusion, clinical trial  3
  8. 8. XCEL-MT-10-02 Biomaterials. 2008 Oct;29(29):3973-82. doi: 10.1016/j.biomaterials.2008.06.026. Epub 2008 Jul 18. The clinical use of enriched bone marrow stem cells combined with porous beta-tricalcium phosphate in posterior spinal fusion. Gan Y, Dai K, Zhang P, Tang T, Zhu Z, Lu J. Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China. 41 patients / 95% posterolateral fusion
  9. 9. XCEL-MT-10-02 Zhonghua Wai Ke Za Zhi. 2008 Apr 1;46(7):493-6. Clinical study of lumbar fusion by hybrid construct of stem cells technique and biodegradable material. [Article in Chinese] Zhang P, Gan YK, Tang J, Hao YQ, Wang Y, Sun YH, Zhu ZA, Dai KR. Department of Orthopaedics, Shanghai Ninth People's Hospital, School of Medicine of Shanghai Jiaotong University, Shanghai 200011, China. Bone marrow mesenchyme stem cells hybridized with beta-tri calcium phosphate 93% fusion Autologous iliac crest bone graft 96% fusion
  10. 10. 11 Title: "Ex Vivo" Expanded Autologous Bone Marrow Mesenchymal Stem Cells Fixed in Allogenic Human Bone Tissue for Spinal Fusion in Spine Degenerative Disease (XCEL-MT-OSTEO-ALPHA)” Target: Degenerative Spondylolisthesis L4-L5 degrees I-II of Meyerding Product: XCEL-MT-OSTEO-ALPHA Promotion: BST (Banc de Sang i Teixits) Source: Agencia Nacional del medicamento XCEL-MT-10-02
  11. 11. XCEL-MT-10-02 Design: Phase I/II, prospective, open (blind assessment), randomized, parallel, only one dose and multicentric Centres / IP: Vall d’Hebron, Hosp Germans Trias i Pujol, Hosp del Mar, Hosp St Pau, ICATME-Dexeus Objectives: 1st: To evaluate viability and safety of the product Second: Assess efficacy through image (CT and XR evaluation of fusion status at 6 and 12m) and clinical assessment( VAS, Oswestry, SF-36)
  12. 12. Experimental study Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
  13. 13. Experimental study Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
  14. 14. Experimental study Focal cryogen insults for inducing osteonecrosis Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
  15. 15. Experimental study Histology of therapeutic model Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
  16. 16. Purpose and hypothesis Purpose Randomized study, compares the spinal fusion obtained after instrumentation and the use of a biologic product (patients MSCs bone marrow fixed in human bone tissue from a donor), with the current procedure that consist in instrumented spinal fusion and the use of each patient’s bone obtained from his/her iliac crest Working hypothesis Proposes that the tissue engineering is valid and useful technique to achieve bone regeneration avoiding iliac crest patient harvesting
  17. 17. 18 Sample: 62 Patients, age18-85a, bout sex. Group A: Surgical fusion using autologous mesenchymal cells expanded “ex vivo” fixed in allogenic osseous matrix (XCEL-MT- OSTEO-ALPHA)” Group B: Surgical fusion using autologous iliac graft XCEL-MT-10-02
  18. 18. • Extracción
  19. 19. Bone marrow aspiration
  20. 20. Bone marrow aspiration
  21. 21. • Extracción
  22. 22. Initial harvest bone marrow Spread Cell Stack Microscopically assessment of the sample celularity and brooding culture Culture andCulture and enlargementenlargement
  23. 23. Volume Reduction (Spin cycle place the MSCc at the bottom of the pack) CellStacks Strict conditions Cèl-lules mesenquimals, previes a la colonització
  24. 24. • Extracción
  25. 25. Implant:Implant: TLIF L4-L5 TLIFTLIF
  26. 26. Implant:Implant: TLIF L4-L5 XCEL-MT-OSTEO-ALPHAXCEL-MT-OSTEO-ALPHA
  27. 27. XR AssessmentXR Assessment independent radiologistindependent radiologist • Molinari score by independent radiologistMolinari score by independent radiologist
  28. 28. CT AssessmentCT Assessment independent radiologistindependent radiologist • Anterior interbody fusion, facet fusion andAnterior interbody fusion, facet fusion and inter transverse process fusioninter transverse process fusion
  29. 29. 2014 status of the study2014 status of the study Centre Selected (CI signature) Selection Failure Random Random On going postIQ Concluded Tto A TTo B 1 15 3 8 4 10 3 2 2 9 4 5 5 3 3 3 12 1 5 6 4 2 4 4 4 2 2 2 2 5 5 1 1 1 1 41 4 19 18 22 8
  30. 30. 007 patient007 patient Radiologist report Posterorolateral multiple graft around rods with continuous bridges more specially in the right side.
  31. 31. 007007 patientpatient
  32. 32. 001 Pacient001 Pacient
  33. 33. BCN Trials
  34. 34. Process to applying MSCs for bone repair
  35. 35. MSCs directly implanted without ex vivo expansion BCN Experience
  36. 36. Non expanded MSCs • Avoid cost and time • Depend on the number and concentration • <1000 cell per cm3 or< 30.000 cells in total • Small volumes range 2 / 4 ml in aspiration • Centrifuging the aspirate before injection • Lack of strict analysis in many current practice
  37. 37. Future MCSs in Orthopedics Looks promising as advances in • Tissue engineering • Biomaterial • Cell biology Converge • To play a major role in the repair and regeneration of musculoskeletal disease and injuries

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