Sessio formacio bst terapies avancades
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This document summarizes several case studies using mesenchymal stem cells (MSCs) for regenerative medicine applications: 1. A pre-clinical study using ovine MSCs implanted in a critical-sized bone defect in sheep tibias showed effective bone regeneration compared to autograft or no cell controls. 2. A large animal study treating induced osteonecrosis of the femoral head in sheep with ovine MSCs implanted at the lesion site showed persistence of cells differentiating into bone and effective treatment compared to controls. 3. A Phase I/IIa clinical trial in humans with osteonecrosis of the femoral head treated with implanted human MSCs showed safety and potential efficacy based on imaging follow-up
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Sessio formacio bst terapies avancades
- 1. TERÀPIES AVANÇADES Dr. Joaquim Vives
- 2. Advanced Therapies Cells (cell therapy)1 Tissues (tissue engineering)3 Genes (gene therapy)2
- 4. Advanced Therapies No immunogenicity 1 donor/patient, 1 dose Expensive Time-consuming 1 donor, several doses Reasonable cost Off-the-self Possible immunogenicity
- 5. Regenerative Medicine Sharpe et al. in: Cell Therapy GxP (2015) [Vives&Carmona eds]
- 7. Potentiality
- 8. Development
- 9. Potentiality&Development Pluripotent: ES cells Totipotent: zygote Multipotent: HPC MSC Oligopotent : lymphoid stem cells Unipotent : germ cells Terminally differentiated cells. i.e. Fibroblasts +POTENTIALITY- DEVELOPMENT
- 10. Blastocyst From Dr. L. Batlle-Morera, CRG
- 16. Fetus
- 18. Adult organism
- 20. Qualities of MSC for clinical use 20 Reis et al (2016) Front Immunol 7, 500 Nombela-Arrieta et al (2011) Nat Rev Mol Cell Biol 12, 126
- 21. From Dr. L. Rodríguez (BST) Dominici, M. et al. (2006). The International Society for Cellular Therapy position statement. Cytotherapy 8, 315–317.
- 23. 23 Wagner, W. et al. (2005). Exp. Hematol. 33, 1402–1416
- 25. Neonatal tissue Oliver-Vila & Coca et al (2015) Cytotherapy
- 26. Potentiality
- 27. Potentiality&Development Pluripotent: ES cells Totipotent: zygote Multipotent: HPC MSC Oligopotent : lymphoid stem cells Unipotent : germ cells Terminally differentiated cells. i.e. Fibroblasts +POTENTIALITY- DEVELOPMENT
- 32. iPSC 32
- 33. Applications BASIC RESEARCH DISEASE MODELLING DRUG SCREENING
- 34. Applications
- 35. Applications Cherry & Daley (2012) Cell 148, 1110
- 36. Cell Culture Technology Sart et al (2014) Cytotechnology 68,709
- 38. Cell Culture Technology Robey et al (2015) Bone 70,87
- 41. Overview of BST’s Advanced Therapies Auto BM-MSC Gonarthrosis Degenerative meniscus Combined with bone scaffolds ONFH Spinal Fusion Pseudoarthrosi sCriopreserved Multiple Sclerosis Spinal cord injury GvHD Cardiomyopathy Proximal femoral fractures in the elderly Combined with bone scaffolds Deficiency of specific immunity Allo BM-MSC (cryopreserved) Allo WJ-MSC (cryopreserved) Virus-specific activated T cells Auto Allo
- 42. Product development overview Caminal et al (2014) New Biotech 31, 492 Codinach et al (2016) Cytotherapy 18, 1197 Soler et al (2016) Knee 23, 647 Vives et al (2015) Cytotherapy 17, 1009 Vives et al (2015) BMC Proceedings 9, O9
- 43. BACKGROUNDOn-going Autologous BM-MSC-based CT at BST Femoral head osteonecrosis • Study name: XCEL-MT-10-01 • EudraCT: 2010-023998-18 • Phase: I-II b • Number of participants: 23/24 • Finished; pending results Spinal fusion • Study name: XCEL-MT-10-02 • EudraCT: 2010-023999-12 • Phase: I-II b • Number of participants: 66 • Finished; pending results Pseudo arthrosis • Study name: XCEL-PSART-01 • EudraCT: 2013-005025-23 • Phase: I-II b • Number of participants: 19/20 • Finished; pending results MSC sources XCEL-MT-OSTEO- ALPHA
- 44. TERÀPIES AVANÇADES Dr. Joaquim Vives
- 45. Case study GLP GMP Study description Experimental system Dose; Route of administration X Proof of concept: Bone regeneration in a model of critical-sized segmental tibial defect Ovis aries (Ripollesa breed, ♀); critical sized defect in tibia 5.8x106 ±0.1x106 oMSC/cc; implant Pilot study: Bone regeneration in a model of femoral head osteonecrosis Ovis aries (Ripollesa breed, ♀); avascular ONFH 5.4x106 ±0.3x106 oMSC/cc; implant X X Biodistribution of hMSC in an immunodeficient mouse model Mus musculus (NRG, ♀ and ♂) 4x105 hMSC; tail-vein injection X X Analysis of protooncogen expression levels, hTERT activity, senescense, G-banding karyotype, and CGH arrays on clinical grade hMSC In vitro assays N/A
- 46. Case study o Experimental groups : Autograft (gold standard) Bone construct without cells (control without cells) XCEL-MT-OSTEO-ALPHA (ovine) (test item) o Procedures: Critical-sized defect (=2.5xØ cm) in tibia. Euthanasia at 3 months post- treatment. Clinical follow-up and histological/biomechanical analysis of the tibias. o Conclusions: Large animal model. Extreme conditions. Safe. Effective as an alternative to autologous bone, avoiding the associated morbidity to the gold standard. Score histology Gold standard (I) Without oMSC (II) With oMSC (III) P < 0,1 Biomechanical Analysis
- 47. Case study o Experimental groups: A: Core decompression (gold standard) B: Bone construct without cells (control without MSC) C: XCEL-MT-OSTEO- ALPHA (ovine) (test item) o Procedures: Induced ONFH 6 weeks pre- treatment. Euthanasia 3 months post- treatment. Clinical follow-up and histological analysis of the femoral heads. o Conclusions: Large animal model. Non-invasive techniques for the clinical follow-up. Safe. Effective.
- 48. Case study o Experimental groups: XCEL-MT-OSTEO-ALPHA (eGFP labelled-ovine MSC) o Procedures: Induced ONFH 6 weeks pre- treatment. Euthanasia 3 months post- treatment. Clinical follow-up and histological analysis of the femoral heads. o Conclusions: Cells applied differentiate into bone and persist.
- 49. Case study GMP GCP Study description Experimental system Dose; Route of administration X X Mesenchymal Stem Cells in Osteonecrosis of the Femoral Head: a Phase I/IIa Clinical Trial (EUDRA- CT:2010-023998-18; ClinicalTrials.gov Id: NCT01605383) Human (♀ and ♂); ARCO grade I or II ONFH 3-10x105 hMSC/cc of bone; impant
- 50. Case study TEP (F18) Pre-Op 6 m 12 m MRI
Editor's Notes
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