Slide 1: Adult Stem Cell Therapy for Adult Nonunions
ADULT STEM CELL THERAPY FOR ADULT NONUNIONS Matthew L. Jimenez, MD Illinois Bone and Joint Institute Lutheran General Hospital
Slide 2: Outline
OUTLINE Review Study Design Review Surgical Technique Clinical Case Examples
Slide 3: Tissue Repair Cells (TRCs)
TISSUE REPAIR CELLS (TRCs) Aastrom Biosciences, Inc. Ann Arbor, MI
Slide 4: The TRC Production Process
THE TRC PRODUCTION PROCESS Small aspirate from patient Office procedure TRCs generate healthy tissues > 200 patients treated to date TRCs produced in AastromReplicell System Centralized GMP manufacturing facility Bone marrow stem cell product in 12 days
Slide 5: Study Design
STUDY DESIGN
Slide 6: United States Phase Fracture Trial
UNITED STATES PHASE 2 FRACTURE TRIAL Objective: Determine Safety of TRC Cell Therapy as an Adjunct for Non-union Fracture Healing Multi-site, Prospective, Consecutive Case Series
Slide 7: United States Phase Fracture Trial: Patients
UNITED STATES PHASE 2 FRACTURE TRIAL Total No. Patients (all sites): 36 Pilot Phase: 11 Patients 7 Subjects have completed 6 months observation (this report) Expanded Phase: 25 Subjects Protocol changes for improved process and data collection
Slide 8: United States Phase Fracture Trial: Primary Endpoint
UNITED STATES PHASE 2 FRACTURE TRIAL Primary Endpoint: 6 months * Frequency and Type of Adverse Events Fracture Healing Cortical bone bridging in 2 orthogonal radiographs Safety Surveillance: 12 Months
Slide 9: Study Inclusion Criteria
STUDY INCLUSION CRITERIA Inclusion Duration of Non-healing: 4 Months Minimum from Original Fracture Reduction Fracture Gap 0-6 cm Distance > 4cm from Joint Atrophic Non-union by Radiographs, CT, Ultrasound
Slide 10: Study Inclusion Criteria
STUDY INCLUSION CRITERIA Acute Open Tibial Fracture Type IIIA or IIIB No Clinical Signs of Infection at Fracture or Operative Site At Least 18 years Old Normal Bone Marrow and Organ Function to Ensure Good Cell Aspirate Inclusion
Slide 11: Study Exclusion Criteria
STUDY EXCLUSION CRITERIA Exclusion Patients Unable to Discontinue Alcohol Abuse; Smoking Discouraged Patients who Need Corticosteroids, NSAIDs, cox-2 Inhibitors or other Anti-inflammatory Therapy after Surgery Genetic Metabolic Bone Disease; Chronic Renal Disease; Diabetes Mellitus
Slide 12: Study Exclusion Criteria
STUDY EXCLUSION CRITERIA Exclusion Patients on Systemic Antibiotics for Suspected Fracture Site Infection Allergies to Specific Cytokines or Animal Proteins Used in ex vivo Cell Production Process
Slide 13: Patient Histories for Nonunions
PATIENT HISTORIES FOR NONUNIONS Gender Age Smoker Bone Cause No. prior surgeries Prior treatment for non-union: History 1 M Caucasian 55 Tibia Auto accident 1 Reamed IM nail, comminuted fracture, bone defects 2 F Caucasian 42 Tibia Leg crushed by feed grinder 1 Locked plate, comminuted fracture, bon
Slide 14: Pilot Study
PILOT STUDY Early Results 7 Patients
Slide 15: Interim Results: Safety
INTERIM RESULTS: Safety Single Surgeon, Single site: 7 patients Safety: No TRC-related Adverse Events Surgical Adverse Events in 2/7 Acute Infections, Resolved, Fractures United No Morbidity at Site of Marrow Aspirate No Change in Serum Biochemistry or White Cell Counts
Slide 16: Interim Results: Safety
INTERIM RESULTS: Safety Single Surgeon, Single site: 7 patients Radiographic Evidence of Bony Callus Formation was Present at 12 and 24 Weeks after Surgery in 4/7 and 7/7 Patients Respectively Serum Alkaline Phosphatase Increased 24% at 2 Weeks Post-op, Indicative of Stimulated Bone Formation
Slide 17: Surgical Technique
SURGICAL TECHNIQUE
Slide 18: Goals of Surgery
GOALS OF SURGERY Create a Stable Mechanical Construct Enhance the Biological Environment Favorable to Bone and Vascular Regeneration
Slide 19: Surgical Goals
SURGICAL GOALS Safely Remove Previous Fixation Device Surgical Exposure Prepare Nonunion
Slide 20: Surgical Goals
SURGICAL GOALS Safely Remove Previous Fixation Device if Any Surgical Exposure Prepare Nonunion
Slide 21: Surgical Goals
SURGICAL GOALS Safely Remove Previous Fixation Device if Any Surgical Exposure Prepare Nonunion
Slide 22: Surgical Goals
SURGICAL GOALS Safely Remove Previous Fixation Device if Any Surgical Exposure Prepare Nonunion
Slide 23: Bone Discontinuity Large Bone Defects
Bone Discontinuity Large Bone Defects
Slide 24: Surgical Goals: Provide Fracture Stability
SURGICAL GOALS Provide Fracture Stability In this Case, Absolute Stability Locked Plate Construct 4.5 Narrow Combi- hole plate
Slide 25: Components for Mixing Allograft with TRCs
COMPONENTS FOR MIXING ALLOGRAFT WITH TRCs Allograft Partially Demineralized Cortical-cancellous 0.5-2.0mm Particle Size
Slide 26: Components for Mixing Allograft with TRCs
COMPONENTS FOR MIXING ALLOGRAFT WITH TRCs Stem Cells TRC's Suspended in Electrolyte Solution with ..5% Human Serum Albumin Standardized cGMP Product Qualified and Containing approx 175 Million TRCs
Slide 27: Combine Cells with Allograft
COMBINE CELLS WITH ALLOGRAFT 60 cc Syringe and 18 Gauge Needle Withdraw Cells Slowly Cells in fluid suspension Slowly Drip the Cells onto the Allograft Gently Mix the Cells and Allograft
Slide 28: Combine Cells with Allograft
COMBINE CELLS WITH ALLOGRAFT 60 cc Syringe and 18 Gauge Needle Withdraw Cells Slowly Cells in fluid suspension Slowly Drip the Cells onto the Allograft Gently Mix the Cells and Allograft
Slide 29: Combine Cells with Allograft
COMBINE CELLS WITH ALLOGRAFT 60 cc Syringe and 18 Gauge Needle Withdraw Cells Slowly Cells in fluid suspension Slowly Drip the Cells onto the Allograft Gently Mix the Cells and Allograft
Slide 30: Combine Cells with Allograft
COMBINE CELLS WITH ALLOGRAFT 60 cc Syringe and 18 Gauge Needle Withdraw Cells Slowly Cells in fluid suspension Slowly Drip the Cells onto the Allograft Gently Mix the Cells and Allograft
Slide 31: Final Combined Product
FINAL COMBINED PRODUCT Apply Vacuum Suction Only After Thorough Mixing has Occurred Allograft Should Appear Moist, and Hold together from the Moisture and the Cells
Slide 32: Final Combined Product
FINAL COMBINED PRODUCT Apply Vacuum Suction Only After Thorough Mixing has Occurred Allograft Should Appear Moist, and Hold together from the Moisture and the Cells
Slide 33: Fracture Has Been Stabilized Prior to Grafting
FRACTURE HAS BEEN STABILIZED PRIOR TO GRAFTING - -Copious Irrigation Prior to Graft Application
Slide 34: Allograft and Stem Cell Mixture Applied to Nonunion Site
ALLOGRAFT AND STEM CELL MIXTURE APPLIED TO NONUNION SITE
Slide 35: Allograft and Stem Cell Mixture
ALLOGRAFT AND STEM CELL MIXTURE - -Do Not Allow Desiccation - -Rapid Soft Tissue Coverage of Mixture
Slide 36: Clinical Case Reviews
CLINICAL CASE REVIEWS
Slide 37: Case #1
CASE # 1 51 Year Old Male MVA Segmental Fracture Pattern Previous Locked Plate Construct (Liss) BMP X 2 + NSAIDs Smoker
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Slide 39: Case #2
CASE #2 73 Year Old Male High Energy Fall Previous Plate Fixation with Autograft Previous Surgical Infection Poor Initial Mechanical Stability
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Slide 42: Case #3
CASE #3 30 Year Old Male Motor Vehicle vs. Pedestrian (High Energy) Segmental Fracture Pattern Previous Locked Plate Construct (Liss)
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Slide 45: Conclusions
CONCLUSIONS Our Preliminary Report Shows that TRC's with Allograft is Safe and Efficacious for Recalcitrant Tibial Nonunions Further Study is Warranted Our Study Enrollment of 36 Patients is Now Nearing Completion
Slide 46: Thank You
THANK YOU