Regenerative Medicine Tim Greene, MD October 10, 2018

REGENERATIVE MEDICINE

Cells

Scaffold Signal

Process of replacing or regenerating human cells, tissue or organs

Orthopedic Applications

• Bone Fractures and Non Unions • Ligaments and Tendons

• Articular Cartilage Damage

• Arthritis

Available Treatments

• PRP – Platelet Rich Plasma

• PRP Plus – Plus = Amniotic Cells

• Stem Cells

Basics of musculoskeletal injury and repair

Starts with the formation of a blood clot & activation of platelets

1. This releases GF & cytokines at

the site 1. This microenvironment results

in chemotaxis of inflammatory cells

2. activation & proliferation of

local progenitor cells.

Platelet Rich Plasma

Components of blood: Plasma

Red Blood Cells White Blood Cells Platelets

PRP

PRP

PRP Plus

• Plus = Amniotic Cells • Extracellular Matrix • Growth Factors • Antimicrobials

Over 100 years of research and use…

Amniotic Membrane – thin lining of the amniotic sack Cord – harvested from umbilical cord, no chorion Viscous – derived from amniotic fluid

Recovered from the placenta of healthy, planned, full-term pregnancy by c-section.

The regenerative qualities of amniotic membrane support the body’s natural healing process.

Amniotic Cells

2. Protection: Acts as an adhesion barrier to protect tendons and nerves

Natural healing properties of Amnion:

1. Regenerative: Rich in Growth Factors and collagen that support tissue growth

3. Improved healing: Reduce inflammation, anti-scarring, anti-microbial

Amnion Matrix: Surgical Indications

Adhesion barrier Kishman (Clev Clinic)

Tendon or Nerve Wrap Revision Ulnar Nerve Gaspar. JSES 2016.

Rotator Cuff Repair Extremities

– Hand/wrist – Foot/ankle

Reconstructive patch

• Pluripotent – Can become any type of cell

• Self-renewal – Able to maintain its own population

Stem Cells

• Embryonic (Fetal Tissue) – Pluripotent

• Can give rise to any cell in the body • Generate an organ

• Mesenchymal (Adult) – Multipotent

• Produces cells of a certain lineage • Produces cell type of where they reside

• Induced Pluripotent (Dedifferentiated) – Taken adults stem cells and made embryonic stem cells

• Amniotic Derived (Fluid, Placenta, Cord Blood) – Intermediate between pluripotent and multipotent

Types of Stem Cells

• Embryonal – Ethical/Legal prohibition – Oncogenic risks

• Induced Pluripotent – Resolves ethical/legal concerns – Oncogenic risks

• Adult (mesenchymal) – Autologous – No ethical/legal issues – No immune response or rejection – Limited differentiation potential

Ability to Use Stem Cells

A few get left back…intentionally

• Our body has some capacity to regenerate and repair tissues when injured.

• Our existing stem cells can help replenish kidney, liver, bone or heart cells.

• Most promising candidate – Safe (autologous) – Most well studied – Readily available

• Bone marrow • Fat • Synovial membranes • Periosteum

– Demonstrated to produce • Cartilage • Bone • Tendon

Adult Stem Cells for Orthopedics

• Harvested • Interim step – regulated by FDA

– Can be concentrated – Cannot be expanded

• Delivered – Cell Therapy

• Harvested and injected to damaged tissue • Cannot replace large defects or organs

– Tissue Engineering • Stem cells seeded on 3D matrix • Replace lost tissue • Sophisticated with promise • No clinical applications

– Unable to vascularize construct

Application of Stem Cells

Bone Marrow Aspiration from the Ilium

Concentrating Bone Marrow

Plasma

Platelets Mesenchymal Stem Cells (MSC) Monocytes Lymphocytes Granulocytes (neutrophils) RBCs

Stromal Vascular

Fraction or Buffy Coat

A. Directly become tissue specific cells – Substitute or replace damaged or lost tissue

B. Directly influence other cells – Regenerate tissue

C. Modulate or eliminate the inflammatory response

How Stem Cells Work

• Moved focus from bone to cartilage, ligament, tendon and muscle – Relative lack of vascularity – Chronicity

• Effective treatment modalities lacking – Tendinosis – Cartilage defects – AVN – Non unions and bone defects

Clinical Applications for Stem Cells in Orthopedics

• Bone • Non-unions and bone defects

– Grafting or injection of stem cells

• AVN – Good results of decompression and stem cells in small/early lesions

• Spinal fusions – Enhancing bone fusion

Successful Applications of Stem Cells in Orthopedics

• Tendon/Ligament to bone healing inferior to bone to bone healing – Enhance healing – Treat chronic inflammation

• Promising outcomes of enhancing repair with stem cell in animal models – Inconsistent

• No good clinical data to support use

Application of Stem Cells for Tendon/Ligament Healing

• Cartilage is avascular – Very poor ability to heal itself – Increased cartilage damage = arthritis – Standard treatment

• Marrow stimulation • Cartilage transplantation

– Non hyaline cartilage

• Enhancing cartilage repair with stem cells – Moved from experimental stages to clinical stages – Studies are limited

Application of Stem Cells for Cartilage Repair

• Promising treatment outcomes for early OA – Small evidence of modest regeneration potential – Potent anti-inflammatory properties

• Problem – Small studies with short-term follow up – Need large scale randomized studies to prove efficacy

Application of Stem Cells for Arthritis

PRP Plus may be better for DJD

• Duration of up to 1 year ! • USA • Europe • Asia

What is our largest unmet need? 35-40 yo with Arthritis

Risk for Abuse of Stem Cells

• Internet marketing for host of ailments

• Snake oil of today “Cures rheumatism, grows hair, gets rid of wrinkles, etc., etc.”

Regenerative Medicine with the use of Stem Cells has tremendous promise !