Third Annual Workshop on Legal, Policy, Regulatory, and Ethical Healthspan Extension February 9th 2018 Stem Cells and Regenerative Medicine for Aging ELLIOT B. LANDER , M.D., F.A.C.S. ELLIOT LANDER MD CO-MEDICAL DIRECTOR AND CO-FOUNDER OF CELL SURGICAL NETWORK CORPORATION AND CALIFORNIA STEM CELL TREATMENT CENTER

CSN CELL SURGICAL NETWORK™ Mission: Quality Stem Cell Therapy should be available everywhere and easily accessible CSN

Disclosures Dr. Lander has ownership in: Cell Surgical Network™ California Stem Cell Treatment Center™ in Rancho Mirage and Beverly Hills Cells On Ice®

Hippocrates 5th Century BC “I will apply, for the benefit of the sick, all measures [that] are required,”

Rancho Mirage Treatment Center

Beverly Hills Treatment Center

CELL SURGICAL NETWORK RESEARCH AFFILIATES OBTAIN TECHNOLOGY AND DATABSE WITH A BRAND LICENSING AGREEMENT CENTERS COLLECT DATA AND MAINTAIN QUALITY STANDARDS OVER 120 LOCATIONS IN 16 COUNTRIES WITH 100 IN THE US OVER 500 PHYSICIANS

BIOLOGIC SURVIVAL DEPENDS ON TWO SYSTEMS DEFENSE AGAINST DAMAGE- OUR IMMUNE SYSTEMS- (WHITE BLOOD CELLS) HEALING FROM DAMAGE- OUR REPAIR SYSTEMS- (STEM CELLS) Enemies of survival: Injuries, radiation, surgery, violence, infection, behavioral (tobacco), overutilization, genetic and epigenetic mental and physical conditions, toxins, cancer, aging.

What Is Regenerative Medicine? Uses stem cells and growth factors Repair or replace damaged and defective tissues and organs Create living and functional tissues (not scar)

What is a Stem Cell? These are repair cells that are “looking for a job” Stem cells can proliferate (replicate into more stem cells) Stem cells can differentiate (turn into other specific cells or tissues) These actions are based on signals (Growth Factors) from damaged tissues

PATIENTS RECEIVE STEM CELLS AS A DRUG OR AS A SURGERY Laboratory cultured (manufactured and occasionally engineered) allogeneic stem cells are bottled and administered in a controlled trial or sold off the shelf for FDA approved indications. Surgeons transfer tissue from a stem cell rich part of the body to a damaged and stem cell deficient area of the body as a lipo-transfer surgical procedure to promote healing .

TYPES OF STEM CELLS EMBRYONIC- ethics, tumors ADULT MESENCHYMAL- bone marrow, adipose, fetal, umbilical Engineered IPS

Bone Marrow Stem Cells Mesenchyme stem cells decline with age:

ADIPOSE DERIVED STEM CELLS

Why Inject Additional Stem Cells? Stem cell BIOAVAILABILITY- dormant cells made available to damaged tissue When additional stem cells are added to injured areas in large numbers they can effect therapeutic changes Can exert local and systemic changes

Source of Adult Mesenchymal Stem Cells ALLOGENEIC- other humans AUTOLOGOUS- (comes from your own body) so has same DNA as host and can’t be rejected. Lower risk of bacterial or viral infection. No MHC class II antigens or costimulatory molecules

Adult Mesenchymal Stem Cells Can Form: Bone Cartilage Muscle Nerve tissue Blood vessels Connective tissue Fat Other

How Do Stem Cells Heal? HOMING PROPERTY- Cells respond to appropriate cytokine signals released from tissue injury, inflammation, degeneration, disease, or cell death. ACTIVATION PROPERTY- Cells promote cytokine mediated paracrine and autocrine effects to repair damaged target tissue. Cells may engraft and trans-differentiate into needed tissue in some cases.

PROPERTIES OF SVF BASED ON HOMING AND ACTIVATION SVF IS REGENERATIVE SVF IS ANTI-INFLAMMATORY SVF IS IMMUNO-MODULATORY

STROMAL VASCULAR FRACTION Pre-adipocytes mesenchymal stem cells Peri-vascular mesenchymal stem cells Hematopoetic stem cells Macrophages T-Reg cells Endothelial cells Red Blood Cells Growth Factors

THE “ORCHESTRA”

SVF AMPLIFIES THE REPAIR SYSTEM

HOW WE PROCURE SVF “MINI” LIPOSUCTION- UNDER LOCAL ANESTHESIA “CLOSED” SYSTEM SEPARATION- 70 MINUTES USING 50CC FAT GMP GRADE COLLAGENASE- WASHED OUT FILTER 100 MICRONS PHOTOMICROGAPH/ EVALUATE VIABILITY AND COUNT

TIME MACHINE™ CENTRIFUGE

TIME MACHINE™ INCUBATOR

Filter through 100 micron filters

4

FDA Compliant If point of care procedure has No risk of disease transmission SVF point of care procedure using patient’s own cells Do not promote therapy or make claims Performed as a surgical procedure (no laboratory) IDE application has been submitted to FDA

SAFETY Over 8000 cases performed by Network at our centers with no serious complications

SAFETY PAPER ON FIRST 1524 PTS A Prospective Safety Study of Autologous Adipose Derived Stromal Vascular Fraction Using a Specialized Surgical Processing System.   Principal Authors: Mark Berman MD, Elliot Lander MD,   Contributing Authors: See Supplemental Table 1: List of affiliates of the Cell Surgical Network have contributed to the database Published in March 2017 American Journal of Cosmetic Surgery

USES OF SVF UNDER IRB Orthopedics Degenerative Diseases Cardiac Diseases Pulmonary Diseases Autoimmune Diseases Urology Neurology Cosmetic Surgery Ophthalmology Cancer

Orthopedics Spinal disk / Arthritis and Chronic back or neck pain Ankle Hip Knee Tendons / Ligaments / Sports Injuries Elbow / Wrist Shoulder

Prior to SVF deployment 4 months after SVF deployment BEFORE AFTER Prior to SVF deployment 4 months after SVF deployment

SVF AND HEALING CONCUSSION DEMENTIA RADIATION DAMAGE PARALYSIS CANCER TREATMENT TRAUMA BONE MARROW DISEASE AGE RELATED DEGENERATION

REPLACE PARTS OR BUY A NEW CAR? “CELLULAR REPAIR”

CELLULAR REPAIR AND AGING HOW DO WE MEASURE IT? IS MEAN TELOMERE LENGTH ACCURATE? WOULD CELL REPAIR MITIGATE THE PHENOTYPE OF AGING HUMAN BEINGS? DO WE DIE WHEN WE RUN OUT OF AN ADEQUATE SUPPLY OF OUR REPAIR CELLS?

PERSONALIZED MEDICINE IS HERE Personal line of stem cells expanded from SVF: Immortalize Industrialize Prevention Intervention

TAKING PERSONALIZED MEDICINE TO THE NEXT LEVEL Screening and detection Risk stratification Chemotherapy selection Pharmacogenomics to choose medications What about personalized treatment using your own DNA?

USE YOUR OWN DNA AS A MEDICINE TO REPAIR CELLS

USING YOUR OWN CELLS AS A MEDICINE Obtain a reserve of your own repair cells with your own DNA. Allows your own custom dosing schemes based on cell number, treatment interval, deployment method. Industrialize- expand and force multiply your own repair cells and reserve huge quantities for a potential “surge” when repair needed.

“BIO-INSURANCE” A REPOSITORY OF YOUR OWN CELLS IS REAL HEALTH INSURANCE Repeat treatments for aging and other degenerative conditions Conditions that require high numbers of cells as a “surge” Creating customized drugs: antibiotic and cancer agents Gene therapy Creating replacement parts (bone marrow and organs)

PROBLEM: LIFETIME ACCUMULATION OF CELLULAR DAMAGE THE NUMBERS GAME PROBLEM: LIFETIME ACCUMULATION OF CELLULAR DAMAGE DEMAND VS. SUPPLY DEMAND FOR REPAIR INCREASE OVER TIME SUPPLY OF HUMAN REPAIR CELLS (QUALITY AND NUMBER) DECREASES OVER TIME

REGULATORY ISSUES The US FDA is authorized to prevent transmission of communicable disease. In 2017, regulations defined your personal cells a DRUG because: SVF adipose derived cells are more than minimally manipulated and are not for homologous use. 1. FDA approved trials 2. SVF will have to be evaluated and produced like mass marketed pharmaceutical product severely restricting access to one’s own cells and prohibiting patients with HIV/hepatitis from access entirely 3. Criminalizes physician care of patients 4. Denies patient’s their constitutional rights (14th Amendment) to their own cells.