Introduction to Stem Cells and Regenerative Medicine

Gregory A. BonfiglioProteus Venture Partners

Woodside Priory School (November 20, 2009)

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Agenda

Introduction to RM - What is Regenerative Medicine? - The Promise of Regenerative Medicine

Stems Cells- What Are They?- What Can They Do?

Tissue Engineering - What Is Tissue Engineering? - What Can Tissue Engineered Products Do?

The Politics of Stem Cells - Controversy Around Human Embryonic Stem Cells - Therapeutic Cloning (SCNT) & Discarded IVF Embryos

Where to Find More Information About RM

INTRODUCTION

1. Why Can’t We Be Like Salamanders?

2. What is Regenerative Medicine?

3. The Promise of Regenerative Medicine

A Salamander Can Regrow Its Leg… …Why Can’t We?

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What is Regenerative Medicine?

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Regenerative Medicine Is Set of Innovative Medical Technologies Based on Stem Cell Biology and Tissue Engineering That Harnesses the Body’s Own Healing Abilities.  

RM Technologies Have The Capacity To: 

1. Cure Diseases (Instead Of Treating Symptoms);

2. Repair or Regenerate Damaged Tissue; 3. Replace Entire Organs; and 4. Restore Function Lost to Disease or Injury.

Promise of Regenerative Medicine:Repairing Nerve Damage

Promise of Regenerative Medicine:Repairing Heart Tissue & Bladders

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Regenerative Medicine: The Next Phase In Healthcare

1800 1900 2000

Prevention

Control &

Removal

Regenerate &

Regrow• Vaccines

• Bacteriology

• Control Germs

• Diagnostics

• Medical Devices

• Pharmacology

• Surgery

• Cell Therapies

• Tissue Engineering

• Regenerative Compounds

Era Of Regenerative Medicine

Very Promising Technology

STEM CELLS

1. What Are They?

− 3 Types of Stem Cells− Sources of Stem Cells

2. What Can They Do? − Therapeutic Applications

What Is A Stem Cell?

Both Long-Term Self Renewal, and

Differentiate Into Specialized Cells

Stem Cells Have 2 Key Characteristics:

1. Repeated Self Renewal

2. Give Rise To Mature, Specialized Cells

Stem Cell

Mature Cell

Type I

Mature Cell

Type II

Progenitor

Differentiation

Stem Cell TypeDifferentiation

AbilitySource

TOTIPOTENT(Germ Layer)

Can Form A Complete Organism

Very Early (1-3 days) Embryos

PLURIPOTENT(Embryonic)

Can Form Any Of The 200 Cell Types In The Body

Blastocyst Placental TissueAmniotic FluidiPS Technology

MULTIPOTENT(Adult)

Can Form Only A Limited Number Of Cell Types

Fetal TissueCord BloodBone Marrow & Fat

Stem Cells: 3 Broad Categories Based On Their Ability To Differentiate

Embryonic Stem Cells (hESCs): Derived From the ICM of the Blastocyst

Remove ICM

Feeder Layer Supports The

Cells

hES Cell LineEstablished

Blastocyst

Inner Cell Mass

Cells Replicate

Pluripotent (Embryonic) Stem Cells: Differentiate Into All 200 Human Cell Types

hESCs Are Very Powerful, But They Can Form… Teratomas (Benign Tumor)

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Mulitpotent (Adult) Stem Cells:Differentiate Into 3 Major Tissue Types

Nerve

Muscle

Blood

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Adult Stem Cells:Derived From Adipose Tissue (Fat) + Bone Marrow

Liposuction

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iPS Stem Cells: Pluripotent Cells Created From a Patient’s Skin Cells

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What Can Stem Cells Do?Restoring Cardiac Function

Current SoC: Surgical Intervention, Medications. Only cure is a heart transplant.

RM Approach: Use of Cell Therapy to Regenerate or Restore Damaged Cardiac Tissue

Other Near Term Indications: Vision Disorders, Diabetes, Spinal Cord Injury

What Can Stem Cells Do? Restoring Vision

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Fabricating anArtificial Cornea

Curing AMD with RPEsTransplant of Corneal Stem Cells

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Cell Therapy Using ECMs To Regrow A Severed Finger

Baseline 12 week

Cell “Therapy”Using ECMs to Regrow Hair

ECMs Produced 20-40% New Hair

TISSUE ENGINEERING

1. What IS Tissue Engineering?

2. What Can Tissue Engineered Products Do?

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Combining Human Cells With BiocompatibleScaffolds To Generate Functional Organs Or Tissues

Tissue Engineering: Cells + Scaffolds

Engineered Bladder: Entire Organ Grown In Lab

Total Cystectomy Ureteral and Urethral Omental/Peritoneal Anastomosis Coverage

Surgically Implant The Neo-Bladder

Neo-Bladder Design• Autologous Bladder Cells

Seeded On Biodegradable Scaffold

• Grown in Lab for 8-10 Weeks

Surgeon sends patient’s biopsy to Tengion.

Surgeon implants the neo-organ which regenerates and becomes functional.

Autologous Neo-organ DevelopmentAutologous Neo-organ Development

Engineered Skin For Diabetic Ulcers

27

Week 0

Week 5

Week 1

Week 8

Week 3

Week 10

5563i

Engineered Skin for Diabetic Foot Ulcers

Clinical Results: Partial-Thickness Burns

Day 0 Day 6 6 Months After Burn

6138F

Using Engineered Skin: Burn Therapy

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New Heart Grown From Adult Stem Cells

University of Minnesota (2008)

Growing A Windpipe From Stem Cells

Tissue Engineered Articular Cartilage

Tissue-engineered Cartilage For Implantation

Bioreactor For Producing Cartilage

4523

Articular Cartilage Surgical Implantation

Potential Engineered Cartilage Products

Pre-formedCartilage

7128E

Cartilage / Anchor Cartilage /

Bone

Shape-to-FitCartilage

Cartilage

Tissue Engineered Ear Reconstruction

7463 (Vacanti et. al., 1992)

6559

TE Humor

The Politics of Stem Cells

1. Controversy Around Human Embryonic Stem Cells

2. Therapeutic Cloning (SCNT) & Discarded IVF Embryos

Research is Controversial

Controversy Resulted In Limited US Funding….

…. And Very Strong Feelings About The Issue

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The Political Cycle of The Controversy

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1998 2001 2005 2008

Time

hESCs Created

Bush BanImposed

CIRM CreatedhESC Ban Lifted

What Is The Controversy About?

1st: The Creation of hESCs Involves The Destruction of Embryos

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• Process Begins With A Human Egg From IVF Clinic or Donor

• Egg Matures To the Blastocyst Stage (8 Days)

• Inner Cell Mass Is Removed

• hESCs Created From The ICM

• Blastocyst Is Discarded

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Blastocyst on Tip Of Needle

What Is The Controversy About?

There Are Over 400,000 Frozen Embryos In Storage…

…Most Will Be Destroyed

IVF Embryos

What Is The Controversy About?

2nd: Nuclear Transfer Can Be Used to Clone Mammals

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Nuclear Transfer

• Process Begins With An Egg

• Nucleus (Genetic Material) Is Removed

• Nucleus From Donor is Inserted

• Egg Is Implanted and Grows To Maturity

Nuclear Transfer: Removing The Nucleus

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Nuclear Transfer: Inserting New Genetic Material

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Result : Dolly The Sheep - 1st Cloned Mammal

Process Has Been Extended To Sheep, Cows, Goats, Pigs, Mice

Could A Human Being Be Cloned?

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How Does This Impact Regenerative Medicine?

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Nuclear Transfer Can Create Patient Specific Cell Lines

Would Eliminate The Need For Immune Suppression Drugs

And Cure Many Diseases

Therapeutic Cloning

The Debate Continues…..

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Cells Are Beautiful Things…

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…Whatever Your Politics

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Where to Find More Information About RM

1. National Institute of Health 2. Professional Organizations: ISSCR, ISCT, TERMIS3. Disease Advocacy Groups: JDRF, Michael J. Fox4. Websites

Others:PenisTestisUterus

Ureter

Valve

Cartilage

Muscle

Trachea

Nerve

Bone

Kidney (epo prod’n and urine)

Bladder (multiple indications)

Vessels (AV shunt, bypass grafts)

Skin

Liver

Breast

Broad Transformational Technology PlatformCompelling medical advances drive product opportunities