bone and cartilage regeneration with cells and tissue engineering products - dr. enric cáceres -...
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Bone and Cartilage regeneration with cells and tissue engineering products
Enric CàceresChair Orthopaedics
Universitat Autònoma de Barcelona
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
The role of mesenchymal stem cells
MSCs Origin
•Bone marrow•Adipose tissue (including fat pad from knee)•Periostium•Synovium•Artery walls
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
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
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
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
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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 MeyerdingProduct: XCEL-MT-OSTEO-ALPHA
Promotion: BST (Banc de Sang i Teixits)
Source: Agencia Nacional del medicamento
XCEL-MT-10-02
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)
Experimental study
Focal cryogen insults for inducing osteonecrosis
Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
Experimental study
Histology of therapeutic model
Lead By Mario Aguirre and Roberto Vélez,Hospital Valle Hebron)
Purpose and hypothesisPurposeRandomized 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
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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
Initial harvest bone marrow
Spread Cell Stack
Microscopically assessment of the sample celularity and brooding culture
Culture and Culture and enlargementenlargement
Volume Reduction (Spin cycle place the MSCc at the bottom of the pack)
CellStacks Strict conditions
Cèl-lules mesenquimals, previes a la colonització
XR AssessmentXR Assessmentindependent radiologistindependent radiologist
• Molinari score by independent radiologistMolinari score by independent radiologist
CT AssessmentCT Assessmentindependent radiologistindependent radiologist
• Anterior interbody fusion, facet fusion and Anterior interbody fusion, facet fusion and inter transverse process fusioninter transverse process fusion
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
007 patient007 patient
Radiologist reportPosterorolateral multiple graft around rods with continuous bridges more specially in the right side.
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