Stem Cell Primer. Hyun Bae, M.D. Professor of Surgery Department of Surgery Director of Education Cedars Spine Center

Transcription

1 Stem Cell Primer Hyun Bae, M.D. Professor of Surgery Department of Surgery Director of Education Cedars Spine Center

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4 Perinatal Stem Cells Perinatal Stem Cells are defined as stem cells that are associated with Pregnancy. Perinatal stem cells demonstrate some of the key markers of Embryonic stem cells such as: Oct-4+ **, Sox-2+ **, Nanog+ ** Perinatal stem cells also demonstrate adult stem cell markers such as but not limited to: CD105+ (endoglin, SH2), CD73+ (SH3), CD90+ (Thy-1), HLA- A,B,C+ (MHC class I)*, CD105+ (endoglin, SH2), CD73+ (SH3), CD90+ (Thy-1), HLA-A,B,C+ (MHC class I)* Therefore, Perinatal Stem Cells are neither adult stem cells nor are they embryonic stem cells and as such require their own classification as Perinatal Stem Cells. Karahuseyinoglu et al, Stem Cells; 25: , Weiss et al, Stem Cells; 24: , * Expressed less by UCM-MSCs, compared to BM-MSCs **Expressed only by UCM-MSCs, not BM-MSCs 6

5 Sources of Stem Cells

6 MSCs have been extracted from virtually all organs Adult bone marrow (Friedenstein, 1965) Dental pulp (Gronthos et al., 2000) Dermis (Young et al., 2001) White fat (Zuk et al., 2001) Synovial membrane (de Bari et al., 2001) Perichondrium (Arai et al., 2002) Pancreas (Hu et al., 2003) Fetal Bone marrow, liver, lung (Anker, 2003) Umbilical cord (Romanov et al., 2003) Umbilical cord blood (Wagner et al., 2005) Adult blood (Mansilla et al., 2006) Placenta (Li et al., 2007) Ear (Gawronska-Kozak et al., 2007) Cornea (Choong et al., 2007) Lung (Lama et al., 2007) Skeletal muscle (Zheng et al., 2007)

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8 Mechanisms of Action

9 ADULT STEM CELL EXOSOME Conventional view of paracrine function soluble proteins are secreted through fusion of secretary granules LOCAL EFFECT RECIPIENT CELL EXOSOMES AS MEDIATORS OF PARACRINE EFFECT _endosomal origin. Exosomes are secreted through fusion of multivesicular bodies with cell membranes They are bilipid membrane vesicles with protein and mrna

10 Products & Technologies

11 Regulation of Tissue Code Fed Reg. 21 Part 1271 Minimally Manipulation Does not require premarket review or notification by FDA. Note: All tissue must undergo strict screening and sterilization processing for safety. U0MzzPtfUYzZTDhtDPb4a6j_BkR6

12 NuCel Amniotic Fluid Stem Cells are present Amnio Clear Amniotic Membrane

13 NuTechMedical.com NuCel FAQ Have cell been characterized and are there confirmed stem cells in this population. To date there has been no characterization performed on this product What studies specifically related to spine and orthopaedics have been completed. there are no studies specifically related to spine and/or orthopaedics (for NuCel)

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15 Buffy Coat White Cells Lymphocytes Neutrophils PRP STEM CELLS

16 7-33 MSC per 1 million nucleated cells Increase MSCs but also increases nucleated cells 3cc vs 60cc 1008 to MSCs 13 M to 128 M Ref. Athrex Develpment

17 Fresh Frozen Cellular Allograft-- Osetecell

18 Selective Immunodepletion NuVasive, Inc. 2010

19 Paradigm Shift Bone Cells (Osteoblasts and Osteocytes) are the preferred cell types for bone repair 2,3,4,5,6

20 BIO 4 _ Next Generation BIO 4 is processed from allograft donor bone using proprietary methods BIO 4 includes all components of natural bone: cancellous bone containing endogenous cells and cortical bone, and periosteum Cancellous bone Scaffold Cancellous bone Cells Cortical bone Signals Periosteum Signals Osiris Data on File

21 Cellular Allograft in Anterior Cervical Discectomy and Fusion (ACDF) Evaluation of Clinical and Radiographic Outcomes from a Prospective Multi-center Study Robert Eastlack 1, Christopher R. Brown 2, Craig Meyer 3. IMAST, July Scripps Clinic, La Jolla, CA 2 Duke University Medical Center, Durham, NC 3 Columbia Orthopaedic Group, Columbia, MO BACKGROUND Prospective, multicenter trial (17 sites) 249 levels (182 patients) 1- (63%) or 2- (37%) level ACDF (C3-T1) 2 year follow-up with radiograph and CT data Data reviewed by 3 independent spine surgeon reviewers SUMMARY OF RESULTS Single Level: 95% fusion (<3 ROM on F/E); 92% fusion (CT) Two Level: 89% fusion (<3 ROM on F/E); 83% fusion (CT) All Levels: 92% fusion (<3 ROM on F/E); 87% fusion (CT) 93% patient satisfaction scores

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23 MSC Allograft vs DBM

24 Commercial Viability

25 bone marrow + antibody beads/magnet Cell Bank to Provide Off the Shelf Solution MPC Highly Expandable + Non-Immunogenic bone cartilage US Bone Repair Patent granted Orthopaedic Products Products For Eye Diseases Isolated Cells Culture-expanded Cells heart muscle pancreas Products For Cardiac Diseases + Diabetes US Composition Patent granted US Manufacturing Process Patent granted Global Use Patents filed Blood vessel 35

26 Bioreactor Cell Processing

27 Phase II Results

28 MPC groups have a significantly greater proportion of patients with a 50% pain reduction with no intervention compared to 24 months Proportion of Patients 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 50% back pain reduction with no 24 months p = p = % 60.9% p = vs. saline 47.8% p = vs. saline p = vs. saline p = vs. saline 10.0% 0.0% Saline 6 million MPCs 18 million MPCs

29 Missing Link Evidence Based Efficacy

30 Mesoblast Phase III Study 60 investigative sites across US and Australia 660 subjects 2 identical protocols: MSB-DR002 MSB-DR003 Only MSB-DR003 will undergo interim analysis Study period (subject): ~15 months Randomization scheme 1:1:1 rexlemestrocel-l + saline rexlemestrocel-l + HA Saline First patient screen target date: 05 March 2015 Last patient screen target date: 09 November 2016

31 THANK YOU

32 Study Comparing Mesenchymal Precursor Cells and Autogenous Iliac Crest Bone Graft for Lumbar Interbody Fusion in a Randomized Controlled Phase 2 FDA Clinical Trial 42Caution: New Drug Limited by Federal (or United States) law to investigational use.

33 MPC Treated Patients Achieved Similar Fusion Success to Iliac Crest Harvested Autograft 100% 90% 88% 86% 80% 75% 75% 75% 70% 60% 63% 63% 67% 67% 63% 50% 50% 40% 38% 30% 20% 10% 0% 3-Month 6-Month 9-Month 12-Month AutoGraft 25 M MPCs 75 M MPCs Fusion definition - Bridging bone, <5 angular motion & < 3 translational motion 43

34 Radiographic Results Over Time Patient Treated with 25M MPCs 1 Month 3 Months 6 Months 9 Months 12 Months 24 Months 44

35 CT Results Over Time Patient Treated with 25M MPCs 3 Months 6 Months 12 Months 36 Months 45

36 12 Month CT Results Patient Treated with 25M MPCs 46