Regenerative

Annu Navani, MD Medical Director, Comprehensive Spine and Sports Ctr Advisor, Le Reve Regenerative Wellness www.cssctr.com

S Disclosures

S None relevant to this talk Regenerative Medicine in News

http://www.foxsportsnor th.com/07/03/12/Platel et-rich-plasma-therapy- big-with- at/landing_timberwolves. html History of Research

2001: Scientists at Advanced Cell Technology cloned 1981: Mouse early stage Embryo. embryonic cells were derived from inner cell mass. 2006: Scientist at UI Chicago find stem 1963: McCulloch and cell characteristics Till illustrated the 1992: Neural stem in umbilical cord presence of self cells were cultured in blood cells. renewing cells in vitro as neurospheres. mouse bone marrow. 2008: Robert Lanza 1995: Dr Mataparkar & Colleagues find 1908: The term 1968: Bone marrow pioneers in adult first human Stem Cell was transplant between 2 stem cell research embryonic cells w/o coined by Russian siblings treated SCID with clinical the destruction of Scientist utilization of an Embryo. Alexander research in body. Makriso. Mistakes “I have not failed, I have just found 10,000 ways that won’t work”

-Thomas A. Edison

S Stem cells can revolutionize medicine, more than anything since antibiotics

-Ronald Reagan

S Why the Need?

S Limitations of surgical solutions

S Limited life span of current spine and orthopedic interventions

S Trend towards natural holistic solutions

S Interest in repair and restoration

S Positive animal, in vitro and in vivo studies Publication is growing Stem cell: Market Growth https://www.pewtrusts.org/en/research-and-analysis/reports/2019/10/17/ Comprehensive Spine and Sports Center

Autologous

S BM- MSCs S AD- MSCs S IPSCs Allogenic

S Growing human cells outside the body

S Many tissues have some undifferentiated cells that will reproduce and grow in the right environment, and nutrients in the culture media

S Researchers are designing equipment to simulate the normal environment of the body

S Laboratory devices that do this are referred to as bioreactors iPSCs

Induced Pluripotent Stem cells are adult cells that have been genetically reprogrammed to an

S Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007

S Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers

S iPSCs are useful tools for drug development and modeling of diseases especially cancer and transplantation

S Tissues derived from iPSCs are identical match to donor and thereby no rejection by the immune system.

S Additional research is needed and is underway. Common Clinical Biologics

S Platelet-rich Plasma

S BMC- MSCs

S ADC- MSCs

S Amniotic tissue PRP

Comprehensive Spine & Sports Center BMAC vs. ADSC Properties of PRP and MSCs

PRP MSCs S Macrophage activation S Secretion of growth factors S Wound healing S Cell proliferation S Collagen Proliferation S Vascularization

S S Anti-inflammatory

S Vasodilation S Anti-apoptic S Vascularization S Immunomodulatory Applications: MSK and Spine

MSK/Ortho Spine S Joints S Discs S Ligaments S Facets S Muscles and S Epidural Tendons S Sacro-iliac S AVN joint S Non union S Sacro- coccygeal joint/bursa

Disc PRP-BMC evidence

Comprehensive Spine and Sports Center Intradiscal Biologic Injection

09/10/18 Comprehensive Spine & Sports Center Demographics: VAS and Years of Pain

09/10/18 Comprehensive Spine & Sports Center Efficacy and Sustainability

S20 patients start, 18 patients at 6 months and 15 at 18 months S>50% relief in VAS up in 93% of patients at 18 months (n=14/15) and in 94% of patients (n=17/18) at 6 months SImprovement in SF 36 up in 93% of patients at 18 months (n=14/15) compared to 100% (n=18/18) at 6 months S 77% patients reported significant flare up after injection that lasted 2-4 weeks (n= 14) at 6 months SMedication use decreased in 80% of patients at 18 months (n=12/15) compared to 89% of patients (n=16/18) at 6 months SNo adverse events SNo hospitalization or spine in 100% of patients. Comprehensive Spine & Sports Center Secondary Outcomes: Disc Biologics

Comprehensive Spine & Sports Center Advantages of Biologics

S Autologous

S Readily available and easily accessible

S Cost effective

S Minimal regulatory barriers- PRP and BM

S Contains multiple growth factors: PDGF, TGF-beta, FGF, IGF-1,2, VEGF, EGF, Il-8, KGF, CTGF

S Contains potential healing cells

S Contains autologous plasma

S Pre-clinical studies show positive effects on tissue repair and restoration Essence

Regenerative Medicine is Precise and complicated, unfamiliar, Systematic unregulated

Success Criterion

Provider Skill Level Indication Procedure

Patient Quality of Selection Success Product S35 chapters S> 50 authors S> 400 figures and tables S> 675 pages Our Experience

S Long lasting and often with resolution S Significant improvements in function and pain S Structural improvements in many S No report of serious complications Future of RM

S 3D Bioprinting

S Biologic-Device combination

S Precision Medicine

S Gene

S Nanotechnology

S Artificial Intelligence

Thank You

Annu Navani, MD [email protected]