David C. Karli, MD, MBA Steadman Clinic Vail, CO 2015

Medical School: University of Maryland

Residency: Harvard Medical School Board Certified Physical Medicine & Rehabilitation

Practice: Harvard Medical School Faculty

Steadman Clinic (Since 2002)

MBA: University of Denver Daniels School of Business

Work with Regenerative Medical Therapies since 2004

Directly involved in treatment of over 8000 patients Via Injection

Surgical Implantation

Biotech Industry Consultant

Founder – Greyledge Technologies, LLC

Primary clinical/research focus to date: Platelet Rich Plasma

Bone Marrow Blood Concentrate

: is a branch of translational research in tissue engineering and molecular biology which deals with the “process of replacing, engineering or reengineering human cells, tissues or organs to restore or establish normal function.”

Taking nonfunctional tissue and making it functional again using biology Systemic

Nutrition, Sleep, Exercise, Supplementation, Hormone and Metabolic Optimization, Psychological Health

Tissue Specific

Cellular Therapy Therapy in which cellular material is injected

into a patient; this generally means intact, living cells; to achieve a therapeutic effect

Platelet White Blood Cell

Autologous (for this talk)

Tissue obtained from the same individual

Allogeneic

Tissue obtained from another individual

Stem Cell Cell that is capable of

giving rise to indefinitely more cells of the same type, and other kinds of cells Adult (Bone Marrow,

Muscle, Fat)

Embryonic

Placental Derived

Constant: The body will attempt to fix itself Will not always succeed…

Some tissues more “efficient” than others In part – secondary

to blood supply:

Skin, muscle – great efficiency

Tendon, ligament – moderate efficiency

Disc, joint cartilage, meniscus – poor efficiency

Basic conditions for healing:

Energy source Glucose (+/- oxygen)

Building blocks for repair

Amino acids Proteins

Replacement cells

Growth Factors

Light switch

Optimal local environment to facilitate repair

All typically carried/modulated by blood

Manipulation of blood tissue into an implantable product which would augment and amplify the body’s capacity to heal itself

More than clotting agents: Anatomy:

Contractible cytoskeleton Granules : contain GFs,

clotting factors, and numerous proteins

When Activated:

Coordinate healing

Proteins released from injured tissue = trigger for activation

Autologous Biotherapies - Phase I:

Biotherapeutic created by whole blood component separation and concentration of platelets and/or White Blood Cells

Implanted to augment tissue healing

Bio therapeutic created by marrow blood component separation and concentration of platelets and/or White Blood Cell Populations

Delivers complex

collection of cells and bioactive proteins that control maintenance of our body to area of injury or disease to stimulate repair Pluripotent cells “Stem-like” cells Stem cells Platelets

Theories/evidence for therapeutic effect: 1. Cells integrate into native tissue and become new

tissue

2. Cells stimulate native cells to proliferate and become new tissue

3. Cells release proteins to induce healing response

4. Cells regulate the local environment to become less toxic (block inflammation)

5. A combination of the above…

Potential/Demand have driven access to biologic therapies (including “stem cells”) - naturally outpacing scientific validation through research

Access to emerging therapies in fee for service model: Low Barrier to entry

Patient Controlled Care… Patient responsible for researching options for care =

Patient Consumer

Should You Investigate Regenerative Medicine?

What Can You Expect?

Tendonitis/tendonopathy/partial thickness tear Shoulder, Elbow, Hip, Knee, Foot/Ankle

Ligamentous injury/tears (MCL/ACL, Ankle, Elbow) Muscle injury (sprains/strains)/tears Bursitis/ITB Osteoarthritis

Knee, Shoulder, Hip, Ankle, Small Joint Knee Meniscal Tears Hip/Shoulder Labral Tears

Plantar fasciitis Spine?

Disc Regeneration?

Arthroscopy

Knee Hip

Is your problem appropriate for treatment? History and Physical Exam

Here is what we know from: Research Anecdotal Application

Safety and Risk Discussion

Your money is applied to buy an outcome: What is the likelihood of success?

8 out of 10 rule

The treatment may not work!

What will the experience be like?

Cellular Harvest is a technical procedure and not without risk Not routinely taught in standard medical training

programs!

How many has your practitioner performed?

Can they do so comfortably?

Cellular implants are likely to do nothing if not implanted accurately and safely.

Easy to perform injections poorly

Technical procedures – not without risk!

Guided injections require extensive and nonstandard training.

Is your practitioner going to guide the implantation?

How many has he/she done?

Are All Created Equal?

Does your practitioner know exactly what is being implanted?

A majority of PRP and BMC has been implanted without quantitative control!

!PRP#/#BMCC#AUTOLOGOUS#BLOOD#PRODUCT#RECORD#

!

FORM&10036.00!MARCH!2013!!!!!!!!!!!!!©!Greyledge!Technologies,!LLC!2010!!

#

!BMCC#/#PRP#ANALYSIS#!

!Platelet!Concentration!!

!_________________________!!Platelets/µL!

!WBC!Concentration!!

!_________________________!!WBC/µL!

!Neutrophils!!

!_________________________NEU/µL!/_________________%!

!

Lymphocytes!!

!

_________________________LYM//µL!/_________________%!

!

Monocytes!!

!

_________________________MONO/µL!/_______________%!

!

Eosinophils!!

!

_________________________EOS/µL!/_________________%!

!Basophils!

!

!_________________________BASO/µL!/_______________%!

!RBC!Concentration!

!

!_________________________!!RBC/µL!

!BMCC!/!PRP!Volume!

!

!_________________________!!cc!

!BMCC!/!PRP!Concentration!!

!__________________________!!!x!Whole!Blood!

!!!

Place!Patient!Label!Here!!!!

!

DATE:!!

!

!PRP#/#BMCC#AUTOLOGOUS#BLOOD#PRODUCT#RECORD#

!

FORM&10036.00!MARCH!2013!!!!!!!!!!!!!©!Greyledge!Technologies,!LLC!2010!!

!

APPROVAL!SIGNATURES:!

______________________________________________! ________________________!

Technician,!Greyledge!Technologies! ! ! ! DATE!

______________________________________________! _______________________!

VVSC!Designated!OR!Staff!Member! ! ! ! DATE!

By#signing#this#checklist#I#(we)#verify#that#all#information#above#has#been#completed#and#that#the#sample#

Identifiers#match#the#patient#medical#record.#!

!BMCC#/#PRP#WHOLE#BLOOD#ANALYSIS#!

!

Platelet!Concentration!!

!

_________________________!!Platelets/µL!

!

WBC!Concentration!!

!

_________________________!!WBC/µL!

!

Neutrophils!!

!

_________________________NEU/µL!/_________________%!

!Lymphocytes!

!

!_________________________LYM/µL!/_________________%!

!Monocytes!

!

!_________________________MONO/µL!/_______________%!

!Eosinophils!

!

!_________________________EOS/µL!/_________________%!

!Basophils!

!

!_________________________BASO/µL!/________________%!

!RBC!Concentration!!

!_________________________!!RBC/µL!

!Whole!Blood!Volume!!

!_________________________!!cc!

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Education:

What to expect Pain Control

Time to improvement

What to watch out for Emergency Contact

Activity Modification

Therapy/Exercise

Follow Up

Autologous, Point of Care Biologics in my opinion are reasonable and work often for appropriate Indications PRP – soft tissue indications

BMC – OA/cartilage/bony indications

PRP and BMC if performed properly are safe procedures

Accurate standardization/quantification of every product should be a necessity Higher quality research, scientific validation and safety

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firmly believed in: bloodletting: bleeding patients, as well as purges using calomel and

other toxic substances

Some even blamed Rush's bleeding for hastening the death of: Benjamin Franklin, as well as George Washington, and

Rush insisted upon being bled himself shortly before his death

Trivia: Why did some patients survive/recover?

Web Search PRP, BMC and location

Educational Symposium (TOBI)

“stem cell clinical trials for …”

Clinical Trials: Clinicaltrials.gov

Eurostemcell.org

Webmd.com

Nationalstemcellfoundation.org

Blogosphere LinkedIn (BOS)