1. REPORT OVERVIEW 16

1.1 Statement of the Report 17
1.2 Target Demographic 19
1.3 Report Sources 19
1.4 Purpose of the Report 20
1.4.1 To Survey Recent MSC Advancements 20
1.4.2 To Provide a “Snapshot” of Global MSC Market 20
1.4.3 To Assess Opportunities for Commercialization 21
1.4.4 To Identify Major Market Players and Assess the Competitive Environment 21
1.4.5 To Identify Existing and Emerging Trends 21
1.4.6 To Identify Critical Opportunities and Threats within the MSC Market 22
1.5 Executive Summary 22
1.6 Introduction 24

2. MESECHYMAL STEM CELLS (MSCS): AN OVERVIEW 26

2.1 The Impact of MSCs on Regenerative Medicine 26
2.2 Timeline of MSC Nomenclature 27
2.3 Sources of MSCs 27
2.3.1 Bone Marrow-Derived MSCs (BM-MSCs) 28
2.3.2 Adipose-Derived MSCs (AD-MSCs) 29
2.3.3 Umbilical Cord-Derived MSCs (UC-MSCs) 29
2.4 Cell Surface Markers in MSCs 30
2.5 In Vitro Differentiation Potentials of MSCs 31
2.6 Soluble Factors Secreted by MSCs 32

3. MANUFACTURE OF MESENCHYMAL STEM CELLS 34

3.1 Methods of Isolation of MSCs 35
3.2 From Conventional Cultures to Bioreactors 36
3.2.1 Monolayer Culture Systems 36
3.2.2 Bioreactor-Based Cell Expansion 37
3.2.3 Stirred Tank Bioreactor 37
3.2.4 Rocking Bioreactor 38
3.2.5 Hollow Fiber Bioreactors 38
3.2.6 Fixed-Bed Bioreactors 39
3.3 Main Features of Commercial Bioreactors 44
3.4 Microcarriers used for the Expansion of MSCs 46
3.5 Downstream Processing of MSCs 48
3.5.1 Cell Detachment and Separation 48
3.5.2 Cell Washing and Concentration 50
3.5.3 Safety and Potency Assays 50
3.5.4 Surface Markers for Identification during MSC Manufacture 50

4. COMPARISON OF AUTOLOGOUS AND ALLOGENEIC MSC MANUFACTURE 52

4.1 Manufacturing Cost Compared 52
4.1.1 Cost Differential 53
4.1.2 Cost of Donor Screening and Testing 53
4.1.3 Cost for Release Testing 54
4.2 Comparison of the Two Business Models 54
4.2.1 Risk of Immune Reaction 54
4.2.2 Risk of Cross Contamination 55
4.2.3 Commercially Attractive Option 55
4.3 Cost Breakdown in MSC Manufacturing 55

4.4 Opportunities for Cost Reduction 57
4.5 Partial Automation vs. Full Automation 58
4.5.1 Partial Automation: The Most Attractive Option 60

5. SMALL SCALE PROCESSING OF MSCS 61

5.1 Model Design 61
5.2 Culture Media 62

6. LARGE-SCALE EXPANSION OF MSCS 67

6.1 The Four Common Bioprocessing Strategies for Large-Scale Expansion 68
6.2 Commonly Used Sources of MSCs for Large-Scale Expansion 69
6.3 The Commonly Used Culture Medium for the Large-Scale Expansion of MSCs 70
6.3.1 Expansion Ratio Achieved with Different Culture Media 70
6.4 Comparison between Large-Scale Bioprocessing Strategies 72
6.5 Contract Manufacturing for Cell Therapies 72
6.5.1 Contract Manufacturing Organizations (CMOs) 73
6.5.2 Contract Development and Manufacturing Organizations (CDMOs) 73
6.5.2.1 Major Services Offered by CMOs 73
6.5.2.2 Regional Distribution of CMOs 74
6.6 Global Cell Therapy Manufacturing Capacity 75
6.6.1 Major Cell Therapy CMOs/CDMOs in the U.S 76
6.6.2 Major CMOs/CDMOs for Cell Therapy Manufacturing in Europe 77

7. ESTIMATED CONSUMPTION OF MSCS IN THE INDUSTRY 78

7.1 Consumption of MSCs in Academic and Preclinical Settings 79
7.2 MSC Consumption in Clinical Settings 79
7.3 Consumption of MSCs by Target Indications in Clinical Trials 80
7.4 Future Consumption through 2030 81
7.4.1 Consumption for MSC Therapeutics 81
7.4.2 Consumption for Engineered Tissues and Organs 81
7.4.3 MSC Consumption by MSC-Derived Products 82
7.4.4 MSC Consumption in Emerging Industries 82
7.5 Cost of MSCs per Patient used in Clinical Trials by Indication 82

8. PUBLISHED SCIENTIFIC PAPERS ON MSCS 84

8.1 Number of Papers on MSCs and iPSCs Compared 85
8.2 Number of Papers on MSCs by Source 87
8.3 Number of Papers Published on Clinical Trials Involving MSCs 88
8.3.1 Number of Papers on Clinical Trials using MSCs for Specific Diseases 89

9. CLINICAL TRIALS OF MSCS, MSC-BASED COVID-19, MSC-EXOSOMES 91

9.1 Analysis of Data from ClinicalTrials.gov 91
9.2 Sources of MSCs for Clinical Trials 92
9.3 Autologous vs. Allogeneic MSCs 93
9.4 Regional Distribution of MSC-Based Clinical Trials 94
9.4.1 Major Countries Involved in MSC-Based Clinical Trials 95
9.5 Types of Funding for MSC-Based Clinical Trials 97
9.6 Types of MSC-Based Clinical Trials 98
9.7 MSC-Based Clinical Trials by Phase of Development 99
9.8 Clinical Trials Involving MSCs for the Treatment of COVID-19 100
9.8.1 MSC-Based COVID-19 Clinical Trials by Geography 100
9.9 Clinical Trials Involving MSC-Derived Exosomes 102
9.10 NIH Funding for MSC Research 103
9.11 CIRM's Funding for MSC Projects 105
9.11.1 CIRM Funding for MSC-Based Clinical Trials 106

10. CURRENT SUB-OPTIMAL CLINICAL OUTCOMES and SOLUTIONS 107

10.1 To Overcome Challenges Arising from MSC Manufacture 107
10.1.1 Heterogeneity in the MSC Product 107
10.2 Cryopreservation and Culture Rescue 109
10.2.1 Bioengineering Solutions to Boost MSC Function 109
10.2.2 Engineering MSCs to Carry Anti-Cancer “Trogan Horses” 111
10.3 Overcoming Clinical Challenges Related to Infusion 112
10.3.1 Local Administration 112
10.3.2 Insufficient Retention and Survival 112
10.3.3 Strategies to Improve Local Administration 112
10.4 To Overcome Clinical Challenges from the Host 113

11. MODIFICATION OF MSCS 115

11.1 Genetic Modification 116
11.1.1 Gene Modification to Improve Migration 116
11.1.2 Gene Modification to Improve Adhesion 116
11.1.3 Genetic Modification to Improve Survival 116
11.1.4 Genetic Modification to Reduce Premature Senescence 117
11.2 Preconditioning Modifications 117
11.2.1 Preconditioning to Improve Migration 117
11.2.2 Preconditioning to Improve Adhesion 118
11.2.3 Preconditioning to Improve Survival 118
11.2.4 Preconditioning to Reduce Senescence 118
11.3 Therapeutic Application of Modified MSCs 118
11.3.1 Modified MSCs for Neurological Conditions 119
11.3.2 Modified MSCs for Cardiovascular Diseases 120
11.3.3 Modified MSCs for Lung Injury 120
11.3.4 Modified MSCs for Diabetes 121

12. MAJOR DISEASES ADDRESSED BY MSCS IN CLINICAL TRIALS 122

12.1 Clinical Trials using MSCs for Autoimmune Diseases 122
12.2 Clinical Trials using MSCs for Cardiovascular Diseases 123
12.3 Clinical Trials using MSCs for Neurodegenerative Diseases 124
12.4 Clinical Trials using MSCs for Bone and Cartilage Diseases 125

13. PRESENT STATUS OF MESENCHYMAL STEM CELL INDUSTRY 127

13.1 Sources of MSCs for Research and Clinical Applications 127
13.2 Allogeneic Products Gaining Traction 128
13.3 MSC-Based Products with Marketing Approval 129
13.3.1 Alofisel 131
13.3.2 Stemirac 132
13.3.3 Stempeucel 132
13.3.4 Temcell HS 132
13.3.5 Neuronata-R 133
13.3.6 Prochymal (Remestemcel-L) 133
13.3.7 Cupistem 133
13.3.8 Cartistem 133
13.3.9 Cellgram-AMI 134
13.3.10 Queencell 134
13.4 Currently Marketed MSC-Based Bone Matrices 134
13.4.1 Osteocel 135
13.4.2 AlloStem 136
13.4.3 Cellentra VCBM 136
13.4.4 HiQCell 137
13.4.5 Trinity ELITE 137

13.4.6 Map3 137
13.4.7 Trinity Evolution 137
13.4.8 Carticel 138
13.4.9 Chondron 138
13.4.10 DeNovo NT 138
13.4.11 Chondrocelect 138
13.4.12 Ossron 139
13.4.13 JACC 139
13.4.14 MACI 139
13.4.15 Ortho-ACI 140
13.4.16 Spherox 140
13.4.17 Ossgrow 140
13.4.18 Cartigrow 141
13.4.19 ViviGen 141
13.4.20 Bio4 141
13.4.21 Cartiform 141
13.5 From Whole Cell MSC Therapy to MSC-Derived Exosome Therapy 142
13.5.1 Advantages of MSC-Derived Exosomes 142
13.5.2 Contents of MSC-Derived Exosomes 142
13.5.3 Exosomes as Diagnostics 143
13.5.4 Exosomes as Drug Delivery Vectors 143
13.6 MSC-Based Therapy for COVID-19 143
13.7 MSC-Based Clean Meat Production 144
13.8 Stem Cell-Based Cosmetics 144
13.8.1 Marketed Stem Cell-Based Cosmetic Products 145

14. MARKET ANALYSIS 153

14.1 Price Tags for MSC-Based Cell Therapy (CT) Treatment 154
14.2 Price Tags for MSC-Based Matrices 155
14.3 Market Size of MSC-Based Therapies 156
14.4 Global Market for MSC-based Therapeutics 157
14.5 Global Demand for Mesenchymal Stem Cells (MSCs) 159
14.5.1 MSCs Required for Academic and Preclinical Research 159
14.5.2 Required MSCs for Clinical Trials 159
14.5.3 MSCs Required for Developing MSC-Based Therapeutics 159
14.5.4 MSCs Required for Developing MSC-Derived Products 160
14.5.5 MSCs Required for Emerging Industries 160
14.5.6 Global Market Size for Mesenchymal Stem Cells 160
14.6 Market Share of MSC-Based Business Segments 162

15. COMPANY PROFILES 164

15.1 101 Bio 164
15.1.1 Exosome Services 164
15.2 Adipomics, Inc. 165
15.3 Aegle Therapeutics 165
15.3.1 Aegle's Platform Technology 166
15.3.1.1 Epidermolysis Bullosa 166
15.4 Aethlon Medical, Inc. 166
15.4.1 Hemopurifier in Cancer 167
15.5 AgeX Therapeutics, Inc. 167
15.5.1 PureStem Technology 167
15.5.2 Induced Tissue Regeneration (iTR) 168
15.5.3 UniverCyte 168
15.6 Alexerion Biotech Corp. 169
15.6.1 Drug Development 169
15.7 AlloSource, Inc. 170

15.7.1 Products 170
15.7.1.1 AlloStem 170
15.8 American CryoStem Corporation 171
15.8.1 Services 171
15.8.1.1 ATGRAFT Fat Storage 171
15.8.1.2 Adult Stem Cell Program 171
15.8.2 Products 171
15.8.2.1 CELECT Tissue Harvesting System 171
15.8.2.2 ATCELL-AD-MSCs 172
15.8.2.3 ACSelerateMAX Growth Medium 172
15.9 American Type Culture Collection (ATCC) 173
15.9.1 Stem Cell Products 173
15.10 AMS Biotechnology, Ltd. (AMSBIO) 174
15.10.1 Products 174
15.11 Anemocyte S.r.l 175
15.11.1 Total GMP Capacity 175
15.11.2 Product Types 175
15.11.3 Manufacturing Services 175
15.12 Anjarium Biosciences 176
15.12.1 Anjarium's Hybridosome Platform 176
15.13 Anterogen, Co., Ltd. 177
15.13.1 Products 177
15.13.1.1 Cupistem Injection 177
15.13.1.2 Queencell Injection 177
15.14 Apceth Biopharma GmbH 178
15.14.1 Global Services 178
15.14.2 Assay Development Services 179
15.15 Aruna Bio 180
15.15.1 AB126 180
15.16 Athersys, Inc. 181
15.16.1 MultiStem 181
15.17 Avalon GloboCare Corp. 182
15.17.1 Avalon's Core Platforms 182
15.18 Axol Bioscience, Ltd. 183
15.18.1 Products 183
15.19 Azymus Therapeutics 184
15.19.1 AZ Platform 184
15.20 BioCat GmbH 185
15.20.1 Exosome Purification Kits 185
15.21 BioFluidica 186
15.21.1 Technology Platform 186
15.22 Bio-Techne 187
15.22.1 Total GMP Capacity 187
15.22.2 Prtoduct Types 187
15.23 BioVision, Inc. 188
15.24 Baylx, Inc. 189
15.24.1 Product Candidates 189
15.25 BrainStorm Cell Therapeutics 190
15.25.1 MSC-NTF Cells 190
15.26 Capricor Therapeutics 191
15.26.1 Exosome Program 191
15.27 Catalent Pharma Solutions 192
15.27.1 Cell Therapy Expertise 192
15.28 CCRM 193
15.28.1 Total GMP Capacity 193
15.28.2 Product Types 193

15.28.3 Manufacturing Services 193
15.29 CellResearch Corporation, Pte Ltd. 194
15.29.1 Umbilical Cord Lining Stem Cells 194
15.30 Celltex Therapeutics Corporation 195
15.30.1 Therapy Services 195
15.31 Ciloa 196
15.31.1 Exosome Customization Technology 196
15.32 Codiak Biosciences 197
15.32.1 engEx Platform 197
15.32.2 exoASO-STAT6 197
15.32.3 exoIL-12 197
15.33 Corestem, Inc. 198
15.33.1 Neuronata-R 198
15.34 CO-DON AG 199
15.34.1 M-ACT 199
15.35 Cognate BioServices, Inc. 200
15.35.1 Total GMP Capacity 200
15.35.2 Product Types 200
15.36 Creative Bioarray 201
15.37 Creative Biolabs 201
15.37.1 Products 202
15.37.2 Services 202
15.38 Cynata Therapeutics, Ltd. 203
15.38.1 Cymerus Platform 203
15.38.2 GvHD 203
15.38.3 Critical Limb Ischemia 204
15.38.4 Asthma 204
15.38.5 Heart Attack 204
15.38.6 Diabetic Wounds 204
15.38.7 Coronary Artery Disease (CAD) 205
15.38.8 Acute Respiratory Distress Syndrome (ARDS) 205
15.38.9 Sepsis 205
15.38.10 Osteoarthritis 205
15.39 DePuy Synthes 206
15.39.1 ViviGen 206
15.40 Direct Biologics 207
15.40.1 ExoFlo 207
15.41 EVerZom 208
15.41.1 Services 208
15.42 Evox Therapeutics, Ltd. 209
15.42.1 Protein Therapeutics - REPLACE 209
15.42.2 RNA Therapeutics - CORRECT 209
15.43 Exerkine Corp. 210
15.43.1 Clinical Development 210
15.43.1.1 Genetic Diseases 210
15.43.1.2 Aging-Associated Diseases 210
15.44 ExoCan Healthcare Technologies, Pvt. Ltd. 211
15.44.1 Technology 211
15.44.1.1 ExoEnrich Exosome Isolation Kit 211
15.44.1.2 ExoEngineering 211
15.45 ExoCoBio, Co., Ltd. 212
15.45.1 Products 212
15.46 Exogenus Therapeutics 213
15.47 EXoPERT 214
15.47.1 EXo-i 214
15.48 Exopharm 215

15.48.1 LEAP Technology 215
15.48.2 Cevaris and Plexaris 215
15.49 Exosome Diagnostics, Inc. 216
15.49.1 ExoDx Prostate Test 216
15.50 ExosomePlus 217
15.51 Exosome Sciences 218
15.51.1 TauSome Biomarker 218
15.52 Exosomics S.p.A 219
15.52.1 ExoRef 219
15.52.2 SeleCTEV Enrichment Kits 219
15.52.3 SoRTEV Enrichment Kit 219
15.53 Fraunhofer Institute for Cell Therapy and Immunology 220
15.53.1 Total GMP Capacity 220
15.53.2 Product Types 220
15.53.3 Manufacturing Services 220
15.54 HansaBioMed Life Sciences, Ltd. 221
15.54.1 Products 221
15.55 Hope Biosciences, LLC 222
15.55.1 Hope's Cell Culture Process 222
15.56 Japan Tissue Engineering, Co., Ltd. 223
15.56.1 JACC 223
15.57 JCR Pharmaceuticals, Co., Ltd. 224
15.57.1 TEMCELL HS Inj. 224
15.58 Kimera Labs, Inc. 224
15.59 Lonza Group Ltd. 225
15.59.1 Total GMP Capacity 225
15.59.2 Product Types 225
15.59.3 Manufacturing Services 225
15.60 Mantra Bio 226
15.60.1 Partnering 226
15.61 Medipost, Co., Ltd. 227
15.61.1 Cartistem 227
15.62 MDimune 228
15.62.1 BioDrone Technology 228
15.63 NanoSomix, Inc. 229
15.63.1 Technology 229
15.64 NanoView Biosciences 230
15.64.1 Products 230
15.64.1.1 ExoView R 100 230
15.64.1.2 ExoView Tetraspanin Kits 230
15.65 NeurExo Sciences 231
15.66 Nipro Corporation 232
15.66.1 Stemirac 232
15.67 Novus Biologicals, LLC 233
15.67.1 Exosomes Research Tools 233
15.68 NuVasive, Inc. 234
15.68.1 Osteocel Family 234
15.69 OmniSpirant Limited 235
15.69.1 Technology 235
15.70 Orthocell, Ltd. 236
15.70.1 Ortho-ATI 236
15.70.2 CelGro 236
15.71 Orthofix Medical, Inc. 237
15.71.1 Trinity ELITE 237
15.71.2 Trinity EVOLUTION 237
15.72 Osiris Therapeutics, Inc. 238

15.72.1 Cartiform 238
15.72.2 Bio4 238
15.73 Pharmicell, Co., Ltd. 239
15.73.1 Cellgram-AMI 239
15.73.2 Stem Cell Culture Media Cosmetics 240
15.74 Pluristem Therapeutics, Inc. 241
15.74.1 Products 241
15.74.2 PLX-PAD 241
15.74.3 PLX-R18 242
15.74.4 PLX-Immune 242
15.74.5 Partnerships and Collaborations 243
15.74.5.1 Collaboration with NASA 243
15.74.5.2 Collaboration with NIAID 243
15.74.5.3 Collaboration with U.S. Department of Defence (DOD) 243
15.74.5.4 License Agreement with Chart Industries, Inc. 243
15.74.5.5 Collaboration with Thermo Fisher Scientific 244
15.74.5.6 Partnership with Cha Biotech 244
15.75 Regeneus, Ltd. 245
15.75.1 HiQCell 245
15.76 Regrow Biosciences, Pvt., Ltd. 246
15.76.1 Ossgrow 246
15.76.2 Cartigrow 246
15.77 ReNeuron 247
15.77.1 Exosome Platform 247
15.78 RoosterBio 248
15.78.1 Products 248
15.78.2 Services 249
15.79 RoslinCT 250
15.79.1 Total GMP Capacity 250
15.79.2 Product Types 250
15.79.3 Manufacturing Services 250
15.80 RTI Surgical, Inc. 251
15.80.1 Map3 Allograft Chips 251
15.81 Sentien Biotechnologies, Inc. 252
15.81.1 SBI-101 252
15.81.2 Pipeline 253
15.82 STEMCELL Technologies, Inc. 254
15.82.1 Products 254
15.83 Stemedica Cell Technologies, Inc. 255
15.83.1 BioSmart Technology 255
15.83.2 Pipeline 255
15.84 Stemmatters Biotechnologia e Medicina Regenerative SA 256
15.85 Stempeutics Research, Pvt., Ltd. 257
15.85.1 Stempeucel 257
15.85.2 Stempeutron 257
15.85.3 Stempeucare (Cutisera) 258
15.86 System Biosciences, LLC 259
15.86.1 Products 259
15.86.2 Services 259
15.87 Takeda Pharmaceuticals U.S.A., Inc. 260
15.87.1 Alofisel 260
15.88 Tempo Bioscience 261
15.88.1 Products 261
15.88.1.1 Human Cell Models 261
15.88.1.2 Services and Alliances 262
15.89 Tavec Pharma 263

15.89.1 Technology 263
15.90 United Therapeutics Corp. 264
15.90.1 Unexisome 264
15.91 Vericel Corporation 265
15.91.1 MACI 265
15.91.2 Carticel 265
15.92 Versatope Therapeutics 266
15.92.1 VT-105 266
15.93 Vesigen Therapeutics, Inc. 267
15.93.1 Technology 267
15.94 Waisman Biomanufacturing 268
15.94.1 Total GMP Capacity 268
15.94.2 Product Types 268
15.94.3 Manufacturing Services 268
15.95 WuXi Advanced Therapies 269
15.95.1 Total GMP Capacity 269
15.95.2 Product Types 269
15.96 XOStem, Inc. 270
15.97 Zen-Bio, Inc. 271
15.97.1 Products 271
15.97.1.1 Human Exosomes 272
15.97.2 Contract Services 273
15.98 Zimmer Biomet 274
15.98.1 Cellentra 274

INDEX OF FIGURES
FIGURE 3.1: Monolayer Culture Systems 36
FIGURE 3.2: Stirred Tank Bioreactor 37
FIGURE 3.3: Rocking Bioreactor 38
FIGURE 3.4: Hollow Fiber Bioreactors 39
FIGURE 3.5: Fixed-Bed Bioreactors 39
FIGURE 3.6: Single-Use Harvestainer for Small Scale Application 49
FIGURE 3.7: Single-Use Harvestainer for Large Scale Application 49
FIGURE 4.1: CoG in MSC Manufacturing 56
FIGURE 4.2: Impact of Head Count on Overall CoG per Batch 57
FIGURE 4.3: CoG Breakdown in Partially-Automated MSC Manufacturing 58
FIGURE 4.4: Cost Breakdown in Fully Automated MSC Manufacturing 59
FIGURE 4.5: Higher Throughput in Partially Automated Facilities 60
FIGURE 5.1: Diagrammatic Representation of SelecT Automated Platform by Sartorius 65
FIGURE 5.2: Model of a Clean Room in a Small-Scale Manufacturing Facility 66
FIGURE 6.1: The Four Common Bioprocessing Strategies 69
FIGURE 6.2: Large-Scale Expansion of MSCs by Source 69
FIGURE 6.3: Commonly used Culture Media in the Large-Scale Expansion of MSCs 70
FIGURE 6.4: Major Services Offered by CMOs 74
FIGURE 6.5: Regional Distribution of CMOs 75
FIGURE 7.1: Share of Published Papers by Type 78
FIGURE 7.2: Consumption of MSCs in Academic and Preclinical Settings 79
FIGURE 7.3: MSC Consumption in Clinical Settings 80
FIGURE 7.4: Consumption of MSCs by Target Indications in Clinical Trials 80
FIGURE 8.1: Number of Published Papers on MSCs between 2010 and 2020 85
FIGURE 8.2: Number of Published Papers for MSCs and iPSCs Compared, 2010-2020 86
FIGURE 8.3: Number of Papers on MSCs by Source 88
FIGURE 8.4: Number of Papers on Clinical Trials Involving MSCs 89
FIGURE 8.5: Percent Share of Specific Diseases in Clinical Trials 90
FIGURE 9.1: Distribution of Clinical Trials involving MSCs across the World, 2020 92
FIGURE 9.2: Clinical Trials Involving MSCs by Source 93
FIGURE 9.3: Clinical Trials Involving Autologous and Allogeneic MSCs 94
FIGURE 9.4: Distribution of MSC-Based Clinical Trials by Geography, 2020 95
FIGURE 9.5: Type of Funding for MSC-Based Clinical Trials 97
FIGURE 9.6: The Three Types of Ongoing MSC-Based Clinical Trials, 2020 98
FIGURE 9.7: MSC-Based Clinical Trials by Phase of Development, 2020 99
FIGURE 9.8: MSC-Based COVID-19 Clinical Trials by Geography 100
FIGURE 10.1: Bioengineering Solutions to Boost the Function of MSC 109
FIGURE 10.2: Bioengineering Solutions for Improving Administration of MSCs 113
FIGURE 10.3: Solutions to Overcome Host Factors 114
FIGURE 11.1: Four Focal Points of Enhancement of MSC's Properties during Modification 115
FIGURE 11.2: The Cycle of Naïve MSCs to Modified MSCs for Clinical Application 119
FIGURE 12.1: Major Diseases Addressed by MSCs in Clinical Trials 122
FIGURE 12.2: Percent Share of Autoimmune Diseases in Clinical Trials using MSCs 123
FIGURE 12.3: Percent Share of MSC by Source in Trials for Cardiovascular Diseases 124
FIGURE 12.4: Percent Shares of Neurodenerative Diseases in Clinical Trials using MSCs 125
FIGURE 12.5: Percent Share of MSC by Source in Trials for Bone and Cartilage Diseases 126
FIGURE 14.1: Percent Share of Marketed CT, GT and TE Products 153
FIGURE 14.2: Percent Share of CT Products by Indication 154
FIGURE 14.3: Market for MSC-Based Cell Therapy Products by Geography, 2020-2027 158
FIGURE 14.4: Global Market for Mesenchymal Stem Cells by Geography, 2020-2027 161
FIGURE 14.5: Market Share of MSCc by Business Segments 163

INDEX OF TABLES
TABLE 2.1: Timeline of MSC Nomeclature 27
TABLE 2.2: Sources of MSCs 28
TABLE 2.3: Advantages and Disadvantages of BM-MSCs 29
TABLE 2.4: Advantages and Disadvantages of AD-MSCs 29
TABLE 2.5: Advantages and Disadvantages of UC-MSCs 30
TABLE 2.6: Positive and Negative Markers for MSCs Derived from Different Sources 30
TABLE 2.7: In Vitro Differentiation Potentials of MSCs 31
TABLE 2.8: Soluble Factors Secreted by MSCs 32
TABLE 3.1: Initial Story of MSCs: A Snapshot 34
TABLE 3.2: Methods of Isolation of MSCs and Corresponding Culture Media 35
TABLE 3.3: A Snapshot of Commercially Available Culture Systems 40
TABLE 3.3: (CONTINUED) 41
TABLE 3.3: (CONTINUED) 42
TABLE 3.3: (CONTINUED) 43
TABLE 3.3: (CONTINUED) 44
TABLE 3.4: Main Features of Commercally Available Bioreactors 45
TABLE 3.5: Microcarriers used for the Expansion of MSCs 46
TABLE 3.5: (CONTINUED) 47
TABLE 3.5: (CONTINUED) 48
TABLE 3.6: Basic Assays for MSCs 50
TABLE 3.7: Cell Surface Markers on MSCs and Fibroblasts 51
TABLE 4.1: Cost of Manufacturing Allogeneic MSCs 52
TABLE 4.2: Cost of Manufacturing Autologous MSCs 53
TABLE 4.3: Comparison of Allogeneic and Autologous Therapies 55
TABLE 4.4: Cost of Goods (CoG) in MSC Manufacturing 56
TABLE 4.5: CoG Breakdown in Partially-Automated MSC Manufacturing 58
TABLE 4.6: Cost Breakdown in Fully Automated MSC Manufacturing 59
TABLE 4.7: Higher Throughput in Partially Automated Facilities 60
TABLE 5.1: Key Process and Cost Assumptions 62
TABLE 5.2: Quality Control Panel with Cost Assessments 63
TABLE 5.3: Additional Supporting Labor Cost Assumptions 63
TABLE 5.3: (CONTINUED) 64
TABLE 5.4: Additional Supporting Facility and Process Assumptions 64
TABLE 5.4: (CONTINUED) 65
TABLE 6.1: Large-Scale Expansion of MSCs by Method, Cell Source and Media 67
TABLE 6.1: (CONTINUED) 68
TABLE 6.2: Expansion Ratio Achieved with Different Culture Media 71
TABLE 6.3: Comparison between Large-Scale Bioprocessing Strategies 72
TABLE 6.4: Regional Distribution of CMOs 74
TABLE 6.5: Global Cell Therapy Manufacturing Capacity 76
TABLE 6.6: Major CDMOs and CMOs in North America 76
TABLE 6.7: Major CDMOs and CMOs in Europe 77
TABLE 7.1: Cost of MSCs per Patient in Clinical Trials by Indication 83
TABLE 8.1: Number of Published Papers on MSCs between 2010 and 2020 84
TABLE 8.2: Number of Papers on MSCs and iPSCs Compared between 2010 and 2020 86
TABLE 8.3: Number of Papers on MSCs by Source 87
TABLE 8.4: Number of Papers on Clinical Trials Involving MSCs, 2010-2020 88
TABLE 8.5: Number of Papers on Trials using MSCs for Specific Diseases, 2010-2020 90
TABLE 9.1: Number of Clinical Trials Involving MSCs by Region as of Apr. 2020 91
TABLE 9.2: Clinical Trials Involving MSCs by Source 93
TABLE 9.3: Clinical Trials Involving Autologous vs. Allogeneic MSCs 94
TABLE 9.4: Distribution of MSC-Based Clinical Trials by Geography, 2020 95

TABLE 9.5: Number of MSC-Based Clinical Trials by Country as of 2020 96
TABLE 9.6: Type of Funding for MSC-Based Clinical Trials, 2020 97
TABLE 9.7: The Three Types of Ongoing MSC-Based Clinical Trials, 2020 98
TABLE 9.8: MSC-Based Clinical Trials by Phase of Development, 2020 99
TABLE 9.9: Number of COVID-19 Clinical Trials by Country 101
TABLE 9.10: Examples of Clinical Trials involving MSC-Derived Exosomes 102
TABLE 9.11: NIH Funding for Research on MSCs, 2020 103
TABLE 9.11: (CONTINUED) 104
TABLE 9.12: CIRM-Funded MSC Projects 105
TABLE 9.13: MSC-Based Clinical Trials Funded by CIRM 106
TABLE 10.1: Examples of Bioengineered MSCs Loaded with Therapeutics 110
TABLE 10.2: Examples of Bioengineered MSCs used as Anti-Cancer Trojan Horses 111
TABLE 11.1: Select Cases of Modified MSC Applications and Therapeutic Outcome 121
TABLE 12.1: Select MSC-Based Clinical Trials for Autoimmune Diseases 123
TABLE 12.2: Select MSC-Based Clinical Trials for Cardiovascular Diseases 124
TABLE 12.3: Select MSC-Based Clinical Trials for Neurodegenerative Diseases 125
TABLE 12.4: Select MSC-Based Clinical Trials for Bone and Cartilage Diseases 126
TABLE 13.1: Examples of Completed Clinical Trials involving MSCs 129
TABLE 13.2: MSC Products with Marketing Approval 130
TABLE 13.3: Marketed Products Containing MSCs in Matrices 135
TABLE 13.4: Disease Conditions Studied using Stem Cell Conditioned Medium (CM) 145
TABLE 13.5: List of Stem Cell-Based Cosmetics 146
TABLE 13.5: (CONTINUED) 147
TABLE 13.5: (CONTINUED) 148
TABLE 13.5: (CONTINUED) 149
TABLE 13.5: (CONTINUED) 150
TABLE 13.5: (CONTINUED) 151
TABLE 13.5: (CONTINUED) 152
TABLE 14.1: Price Tags of MSC-Based Approved CT Products 155
TABLE 14.2: Price Tags for Select MSC Progenitor-Based Products 156
TABLE 14.3: Global Market for MSC-Based Cell Therapy by Geography, 2020-2027 158
TABLE 14.4: Global Market for Mesenchymal Stem Cells by Geography, 2020-2027 161
TABLE 15.1: Alexerion's Exosome-Based Pipeline 169
TABLE 15.2: BrainStorm's Product Pipeline 190
TABLE 15.3: Celltex Therapeutics' Clinical Trials 195
TABLE 15.4: The Cellgram Pipeline from Pharmicell 239
TABLE 15.5: Pluristem's Clinical Pipeline 242
TABLE 15.6: Sentien's Pipeline 253
TABLE 15.7: Stemedica's Clinical Pipeline 256