Table of Contents

EXECUTIVE SUMMARY…………………………………………………………………………. ES-1
i. Methodology……………………………………………………………………….. ES-2
1. TISSUE ENGINEERING AND CELLULAR THERAPY TOOLS AND TECHNIQUES…………………………………………………………………………………. 1-1
1.1 Biomaterials…………………………………………………………………………… 1-1
1.1.1 Biologically Derived Biomaterials ……………………………….. 1-1
1.1.1.1 Collagen …………………………………………………… 1-2
1.1.1.2 Xenogenic Tissue………………………………………. 1-2
1.1.2 Genetically Engineered Biomaterials…………………………… 1-2
1.1.2.1 Deoxyribonucleic Acid Transfection Vectors ….. 1-3
1.1.2.2 Genetically Manipulated Cells ……………………… 1-3
1.1.2.3 Three-Dimensional Polymer Technology ………. 1-3
1.1.2.4 Transgenics………………………………………………. 1-4
1.1.2.5 Fibroblasts………………………………………………… 1-4
1.1.2.6 Immortalized Neural Stem Cells…………………… 1-4
1.1.2.7 Gene Activated Matrices …………………………….. 1-5
1.1.3 Hybrid Biomaterials ………………………………………………….. 1-5
1.1.4 Synthetic Biomaterials………………………………………………. 1-6
1.1.5 Scaffolds…………………………………………………………………. 1-6
1.1.6 Vascular Grafts………………………………………………………… 1-9
1.2 Cell Culture Technology ………………………………………………………… 1-10
1.2.1 Bioreactors ……………………………………………………………. 1-10
1.2.1.1 Flatbed Perfusion Systems ……………………….. 1-11
1.2.1.2 Hollow Fiber Bioreactor Systems ……………….. 1-12
1.2.1.3 Cell Suspension Systems………………………….. 1-12
1.2.1.4 Disposable Bioreactors …………………………….. 1-13
1.3 Stem Cell Technology …………………………………………………………… 1-13
1.3.1 Cell Extraction and Expansion………………………………….. 1-13
1.4 Immunoisolation Technology………………………………………………….. 1-15
1.4.1 Chimeric Immunity………………………………………………….. 1-16
1.4.2 Cell Encapsulation Technology ………………………………… 1-16
2. EMERGING APPLICATIONS OF TISSUE ENGINEERING FOR CARDIOVASCULAR DISEASE MANAGEMENT ………………………………… 2-1
2.1 Cellular Therapy and Tissue Engineering…………………………………… 2-2
2.1.1 Skeletal Myoblasts …………………………………………………… 2-3 2015 Medtech Insight i #A427
U.S. Markets for Biologic and Tissue Engineered
Devices – Cardiovascular and Neurological Products Table of Contents
2.1.2 Bone Marrow-Derived Stem Cells ………………………………. 2-4
2.1.3 Adipose Tissue-Derived Stem Cells ……………………………. 2-4
2.1.4 Cardiac Stem Cells…………………………………………………… 2-6
2.1.5 Human Embryonic Stem Cells……………………………………. 2-6
2.1.6 Induced Pluripotent Stem Cells ………………………………….. 2-8
2.2 Cellular Therapy Administration ……………………………………………….. 2-8
2.3 Clinical Experience with Stem Cell-Based Myocardial Tissue Repair and Regeneration…………………………………………………………………. 2-12
2.4 Cellular Therapies for Myocardial Repair and Regeneration in Development ……………………………………………………………………….. 2-13
2.4.1 Athersys ……………………………………………………………….. 2-15
2.4.2 Baxter…………………………………………………………………… 2-15
2.4.3 Bioheart, Inc. …………………………………………………………. 2-16
2.4.4 Capricor Therapeutics …………………………………………….. 2-16
2.4.5 Cytori Therapeutics ………………………………………………… 2-17
2.4.6 Mesoblast Ltd. ……………………………………………………….. 2-18
2.4.7 NeoStem ………………………………………………………………. 2-19
2.4.8 Osiris Therapeutics ………………………………………………… 2-20
2.4.9 Terumo Corporation ……………………………………………….. 2-21
2.4.10 Vericel ………………………………………………………………….. 2-21
2.4.11 Conceivable Regulatory Timetable……………………………. 2-22
2.5 Emerging Cellular Therapies for Limb Salvage in Critical Limb Ischemia Patients …………………………………………………………………. 2-27
2.5.1 Therapeutic Angiogenesis……………………………………….. 2-27
2.5.1.1 Growth Factor/Gene-Based Angiogenic Therapy …………………………………. 2-29
2.5.1.2 Stem Cell-Based Angiogenic Therapy…………. 2-31
2.5.1.3 Therapeutic Angiogenesis Products in Development …………………………………………… 2-32
2.5.1.3.1 Biomet Biologics …………………… 2-33
2.5.1.3.2 Harvest Technologies ……………. 2-33
2.5.1.3.3 Pluristem Therapeutics ………….. 2-34
2.5.1.3.4 Taxus Cardium Pharmaceuticals Group …………. 2-35
2.5.1.4 Conceivable Regulatory Timetable……………… 2-35
2.6 Bioengineered Vascular Conduits …………………………………………… 2-36
2.6.1 Products in Development ………………………………………… 2-38 2015 Medtech Insight ii #A427
U.S. Markets for Biologic and Tissue Engineered
Devices – Cardiovascular and Neurological Products Table of Contents
2.6.2 Conceivable Regulatory Timetable……………………………. 2-40
2.7 Current and Emerging U.S. Market for Cardiovascular Disease-Related Tissue Engineering and Cellular Therapy Products …………………… 2-40
Exhibit 2-1: Comparative Advantages and Disadvantages of Selected Stem Cell Grafts for Myocardial Repair and Regeneration……………………………………………… 2-9
Exhibit 2-2: Selected Myocardial Cellular Repair and Regeneration Therapies in Development……………………………………………………………………………………….. 2-23
Exhibit 2-3: Estimated Growth of Potential Myocardial Cellular Repair and Regeneration Caseloads, U.S., 2017-2020 …………………………………………………. 2-28
Exhibit 2-4: Estimated Growth of Potential Therapeutic Angiogenesis Cellular Therapy Caseloads, U.S., 2017-2022…………………………………………………………. 2-37
Exhibit 2-5: Estimated Growth of Potential Bioengineered Vascular Graft Caseloads, U.S., 2017-2022……………………………………………………………………… 2-41
Exhibit 2-6: Tissue Engineered Cardiac and Vascular Products, Expected Product Launch, by Indication……………………………………………………………………………….. 2-44
Exhibit 2-7: Tissue Engineered Cardiac and Vascular Products, Estimated Market Forecast, 2017 and 2022………………………………………………………………………….. 2-47
3. EMERGING APPLICATIONS OF TISSUE ENGINEERING FOR NEUROLOGICAL DISEASE MANAGEMENT …………………………………….. 3-1
3.1 Types of Cells Used for Cellular Therapies in Development …………. 3-1
3.1.1 Bone Marrow-Derived Stem Cells ………………………………. 3-2
3.1.2 Adipose Tissue-Derived Stem Cells ……………………………. 3-2
3.1.3 Embryonic Stem Cells ………………………………………………. 3-3
3.1.4 Induced Pluripotent Stem Cells ………………………………….. 3-4
3.1.5 Mesenchymal Stem Cells………………………………………….. 3-4
3.1.6 Neural Stem Cells ……………………………………………………. 3-5
3.2 Emerging Stem Cell-Based Therapies for Alzheimer’s Disease…….. 3-5
3.2.1 Cellular Therapies in Development for Alzheimer’s Disease…………………………………………………. 3-6
3.2.1.1 Chinese Academy of Military Medical Sciences ………………………………………. 3-6
3.2.1.2 Medipost…………………………………………………… 3-7
3.2.1.3 Neuralstem……………………………………………….. 3-7
3.2.1.4 StemCells, Inc. ………………………………………….. 3-7
3.2.2 Conceivable Regulatory Timetable……………………………… 3-8 2015 Medtech Insight iii #A427
U.S. Markets for Biologic and Tissue Engineered
Devices – Cardiovascular and Neurological Products Table of Contents
3.3 Emerging Stem Cell-Based Therapies for Parkinson’s Disease…….. 3-8
3.3.1 Cellular Therapies for Parkinson’s Disease in Development ……………………………………………………… 3-11
3.3.1.1 Bundang CHA Hospital …………………………….. 3-11
3.3.1.2 Fondazione IRCCS Ca’Granda, Ospedale Maggiore Policlinico …………………………………. 3-11
3.3.1.3 Instituto de Medicina Regenerativa/Ageless Regenerative Institute ………………………………. 3-12
3.3.1.4 International Stem Cell Corporation ……………. 3-12
3.3.1.5 Neuralstem……………………………………………… 3-13
3.3.2 Conceivable Regulatory Timetable……………………………. 3-13
3.4 Emerging Stem Cell-Based Therapies for Spinal Cord Injury………. 3-13
3.4.1 Spinal Cord Injury Cellular Therapies in Development …. 3-16
3.4.1.1 Bukwang Pharmaceutical………………………….. 3-16
3.4.1.2 The General Hospital of Chinese Armed Police Forces…………………………………………… 3-16
3.4.1.3 Hospital Sao Rafael………………………………….. 3-17
3.4.1.4 Neuralstem……………………………………………… 3-17
3.4.1.5 Neurogen Brain and Spine Insitute……………… 3-17
3.4.1.6 Pharmicell ………………………………………………. 3-18
3.4.1.7 StemCells, Inc. ………………………………………… 3-18
3.4.1.8 Translational Biosciences………………………….. 3-19
3.4.2 Conceivable Regulatory Timetable……………………………. 3-19
3.5 Emerging Stem Cell-Based Therapies for Post-Ischemic Stroke …. 3-20
3.5.1 Stem Cell Therapies for Ischemic Stroke in Development ……………………………………………………… 3-22
3.5.1.1 Athersys …………………………………………………. 3-22
3.5.1.2 Ecron Acunova………………………………………… 3-24
3.5.1.3 International Stem Cell Corporation ……………. 3-24
3.5.1.4 Pharmicell ………………………………………………. 3-24
3.5.1.5 ReNeuron, Ltd. ………………………………………… 3-25
3.5.1.6 SanBio……………………………………………………. 3-25
3.5.1.7 Stemedica ………………………………………………. 3-26
3.5.1.8 Stempeutics…………………………………………….. 3-26
3.5.1.9 University of Irvine……………………………………. 3-27
3.5.2 Conceivable Regulatory Timetable……………………………. 3-27 2015 Medtech Insight iv #A427
U.S. Markets for Biologic and Tissue Engineered
Devices – Cardiovascular and Neurological Products Table of Contents
3.6 Potential U.S. Market for Neurological Disease-Related Cellular Therapy Products …………………………………………………………………. 3-28
Exhibit 3-1: Estimated Growth of Potential Early-Stage Alzheimer’s Cellular Therapy Caseloads, U.S., 2015-2020…………………………………………………………… 3-1
Exhibit 3-2: Estimated Growth of Early-Stage Parkinson’s Disease Cellular Therapy Caseloads, U.S., 2015-2020…………………………………………………………. 3-10
Exhibit 3-3: Estimated Growth of Potential Spinal Cord Injury Cellular Therapy Caseloads, U.S., 2015-2020……………………………………………………………………… 3-16
Exhibit 3-4: Estimated Growth of Potential Ischemic Stroke Cellular Therapy Caseloads, U.S., 2015-2020……………………………………………………………………… 3-22
Exhibit 3-5: Tissue Engineered Neurological Disease Products, Expected Product Launch, by Indication……………………………………………………………………………….. 3-31
Exhibit 3-6: Tissue Engineered Neurological Disease Products, Estimated Market Forecast, 2020………………………………………………………………………………………… 3-35
APPENDIX: COMPANY LISTING……………………………………………………………… A-1
BIBLIOGRAPHY ……………………………………………………………………………………… B-1