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WPS Presentation - Intro to RM (GAB; Nov 2010)


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An introduction to Regenerative Medicine.

An introduction to Regenerative Medicine.

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  • Red blood cells are red only because they contain a protein chemical called hemoglobin which is bright red in color. Hemoglobin contains the element Iron, making it an excellent vehicle for transporting oxygen and carbon dioxide. As blood passes through the lungs, oxygen molecules attach to the hemoglobin. As the blood passes through the body's tissue, the hemoglobin releases the oxygen to the cells.
  • Pre-op: corneal stem cell failure, caused by the inherited disease ANIRIDIA (note blood vessels & opacity). Post-op: Successful transplant of an ALLOGENEIC cultured corneal stem cell graft. Opacity will clear with time. Vision has improved from barely perceiving hand movement to reading the top line of an eye test chart. To date, over 350 patients have been treated globally (autologous if one good eye OR otherwise allogeneic) with an approx. 70% overall success rate. ----------------------------------Stanford Bio-X (9/06): The artificial cornea is made of a dual-network hydrogel with a clear center and peripheral pores. Cells infiltrate the pores and secrete collagen, which integrates the artificial cornea into the surrounding natural tissue. -----------------------------------Using RPEs to Cure Macular Degeneration
  • Apligrafr is supplied as a bi-layered cell therapy. Like human skin, Apligraf consists of living cells and structural proteins. The lower dermal layer combines bovine type 1 collagen and human fibroblasts (dermal cells), which produce additional matrix proteins. The upper epidermal layer is formed by promoting human keratinocytes (epidermal cells) first to multiply and then to differentiate to replicate the architecture of the human epidermis. Unlike human skin, Apligraf does not contain melanocytes, Langerhans' cells, macrophages, and lymphocytes, or other structures such as blood vessels, hair follicles or sweat glands.
  • In the left photo, the heart chambers are labelled. Ao: aorta. LV: left ventricle. RV: right ventricle. LA: left atrium. RA: right atrium. Middle photo: arrows indicate the border between areas where cells remain (pink) and where they have been removed (white). Right photo: The heart matrix after all cells have been removed.In 2008, University of Minnesota researchers created a beating heart in the laboratory. Using detergents, they stripped away the cells from rat hearts until only the nonliving matrix, or "skeleton," was left; they then repopulated the matrix with fresh heart cells. To remove cells from fresh rat hearts, the researchers pumped solutions of detergents through the network of blood vessels that normally nourish the organ. The treatment popped all the cells like balloons and washed away the debris, leaving the matrix of protein fibers that form the backbone of a living heart's connective tissue. It's called the extracellular matrix, or ECM."We just took nature's own building blocks to build a new organ," says Ott. Still, "When we saw the first contractions we were speechless."The naked ECMs looked strikingly like "ghost hearts": eerily white, rubbery "skeletons" that retained the organ's original 3-D structure. Among the surviving features was the tubing of blood vessels, which came in handy later.Next, the team removed hearts from newborn rats and minced them, liberating a motley crew of adult and undifferentiated cells. The mix contained stem cells and progenitor cells--which have less potential than stem cells but can still become multiple cell types--along with adult heart muscle cells and many other types.
  • 8-cell human blastocyst (embryo) on the head of a pin
  • Transcript

    • 1. Introduction toStem Cells and Regenerative Medicine Gregory A. Bonfiglio Proteus Venture Partners Woodside Priory School (November 20, 2009)
    • 2. 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 CONFIDENTIAL 2
    • 3. INTRODUCTION1. Why Can’t We Be Like Salamanders?2. What is Regenerative Medicine?3. The Promise of Regenerative Medicine
    • 4. A Salamander Can Regrow Its Leg… …Why Can’t We? CONFIDENTIAL 4
    • 5. What is Regenerative Medicine? 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. CONFIDENTIAL 5
    • 6. Promise of Regenerative Medicine: Repairing Nerve Damage
    • 7. Promise of Regenerative Medicine:Repairing Heart Tissue & Bladders
    • 8. Regenerative Medicine: The Next Phase In Healthcare 1800 1900 2000 Control & RegeneratePrevention Removal & Regrow• Vaccines • Diagnostics • Cell Therapies• Bacteriology • Medical Devices • Tissue Engineering• Control • PharmacologyGerms • Regenerative • Surgery Compounds Era Of Regenerative Medicine CONFIDENTIAL 8
    • 9. Very Promising Technology
    • 10. STEM CELLS1. What Are They? − 3 Types of Stem Cells − Sources of Stem Cells2. What Can They Do? − Therapeutic Applications
    • 11. What Is A Stem Cell?Stem Cells Have 2 Key Characteristics: 1. Repeated Self Renewal 2. Give Rise To Mature, Specialized Cells Mature Cell Stem Type I Cell Progenitor Differentiation Mature CellBoth Long-Term Self Renewal, and Type IIDifferentiate Into Specialized Cells
    • 12. Stem Cells: 3 Broad Categories Based On Their Ability To Differentiate DifferentiationStem Cell Type Source AbilityTOTIPOTENT Can Form A Complete Very Early (1-3 days)(Germ Layer) Organism Embryos BlastocystPLURIPOTENT Can Form Any Of The Placental Tissue 200 Cell Types In The (Embryonic) Body Amniotic Fluid iPS Technology Can Form Only A Fetal TissueMULTIPOTENT Limited Number Of Cord Blood (Adult) Cell Types Bone Marrow & Fat
    • 13. Embryonic Stem Cells (hESCs): Derived From the ICM of the Blastocyst Remove ICM Blastocyst Feeder Layer Supports The Cells Cells ReplicateInner Cell Mass hES Cell Line Established
    • 14. Pluripotent (Embryonic) Stem Cells:Differentiate Into All 200 Human Cell Types
    • 15. hESCs Are Very Powerful, But They Can Form… Teratomas (Benign Tumor)
    • 16. Mulitpotent (Adult) Stem Cells:Differentiate Into 3 Major Tissue Types Nerve Muscle Blood CONFIDENTIAL 16
    • 17. Adult Stem Cells: Derived From Adipose Tissue (Fat) + Bone MarrowLiposuction CONFIDENTIAL 17
    • 18. iPS Stem Cells:Pluripotent Cells Created From a Patient’s Skin Cells CONFIDENTIAL 18
    • 19. What Can Stem Cells Do? Restoring Cardiac FunctionCurrent 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 CONFIDENTIAL 19
    • 20. What Can Stem Cells Do? Restoring Vision Transplant of Fabricating an Curing AMD with RPEsCorneal Stem Cells Artificial Cornea CONFIDENTIAL 20
    • 21. Cell TherapyUsing ECMs To Regrow A Severed Finger CONFIDENTIAL 21
    • 22. Cell “Therapy” Using ECMs to Regrow HairBaseline 12 week ECMs Produced 20-40% New Hair
    • 23. TISSUE ENGINEERING1. What IS Tissue Engineering?2. What Can Tissue Engineered Products Do?
    • 24. Tissue Engineering: Cells + Scaffolds Combining Human Cells With Biocompatible Scaffolds To Generate Functional Organs Or Tissues CONFIDENTIAL 24
    • 25. Engineered Bladder: Entire Organ Grown In Lab Neo-Bladder Design• Autologous Bladder Cells SeededOn Biodegradable Scaffold• Grown in Lab for 8-10 Weeks Surgically Implant The Neo-Bladder Total Cystectomy Ureteral and Urethral Omental/Peritoneal Anastomosis Coverage
    • 26. Autologous Neo-organ Development Surgeon sends patient’s biopsy to Tengion. Surgeon implants the neo- organ which regenerates and becomes functional.
    • 27. Engineered Skin For Diabetic Ulcers 27
    • 28. Engineered Skin for Diabetic Foot Ulcers Week 0 Week 1 Week 3 Week 5 Week 8 Week 105563i
    • 29. Using Engineered Skin: Burn Therapy Clinical Results: Partial-Thickness Burns Day 0 Day 6 6 Months After Burn6138F
    • 30. New Heart Grown From Adult Stem Cells University of Minnesota (2008) 30
    • 31. Growing A Windpipe From Stem Cells
    • 32. Tissue Engineered Articular Cartilage Bioreactor For Tissue-engineered Producing Cartilage Cartilage For Implantation4523
    • 33. Articular Cartilage Surgical Implantation
    • 34. Potential Engineered Cartilage Products Pre-formed Cartilage Shape-to-Fit Cartilage Cartilage Cartilage / Anchor Cartilage / Bone7128E
    • 35. Tissue Engineered Ear Reconstruction7463 (Vacanti et. al., 1992)
    • 36. TE Humor6559
    • 37. The Politics of Stem Cells1. Controversy Around Human Embryonic Stem Cells2. Therapeutic Cloning (SCNT) & Discarded IVF Embryos
    • 38. Research is Controversial
    • 39. Controversy Resulted In Limited US Funding….
    • 40. …. And Very Strong Feelings About The Issue CONFIDENTIAL 40
    • 41. The Political Cycle of The ControversyhESCs Created hESC Ban Lifted CIRM Created Bush Ban Imposed 1998 2001 2005 2008 Time CONFIDENTIAL 41
    • 42. What Is The Controversy About?1st: The Creation of hESCs Involves The Destruction of Embryos • 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 CONFIDENTIAL 42
    • 43. What Is The Controversy About?Blastocyst on Tip Of Needle IVF Embryos There Are Over 400,000 Frozen Embryos In Storage… …Most Will Be Destroyed CONFIDENTIAL 43
    • 44. What Is The Controversy About? 2nd: Nuclear Transfer Can Be Used to Clone Mammals Nuclear Transfer• Process Begins With AnEgg• Nucleus (GeneticMaterial) Is Removed• Nucleus From Donor isInserted• Egg Is Implanted andGrows To Maturity CONFIDENTIAL 44
    • 45. Nuclear Transfer: Removing The Nucleus CONFIDENTIAL 45
    • 46. Nuclear Transfer: Inserting New Genetic Material CONFIDENTIAL 46
    • 47. Result : Dolly The Sheep - 1st Cloned MammalProcess Has Been Extended To Sheep, Cows, Goats, Pigs, Mice
    • 48. Could A Human Being Be Cloned? CONFIDENTIAL 48
    • 49. How Does This Impact Regenerative Medicine? Therapeutic CloningNuclear Transfer CanCreate Patient SpecificCell LinesWould Eliminate TheNeed For ImmuneSuppression DrugsAnd Cure ManyDiseases CONFIDENTIAL 49
    • 50. The Debate Continues….. CONFIDENTIAL 50
    • 51. Cells Are Beautiful Things… CONFIDENTIAL 51
    • 52. …Whatever Your Politics CONFIDENTIAL 52
    • 53. Where to Find More Information About RM 1. National Institute of Health 2. Professional Organizations: ISSCR, ISCT, TERMIS 3. Disease Advocacy Groups: JDRF, Michael J. Fox 4. Websites
    • 54. Broad Transformational Technology PlatformCompelling medical advances drive product opportunities Trachea Muscle Breast Valve Liver Vessels (AV shunt, bypass grafts) Nerve Kidney Ureter (epo prod’n and urine) Bone Bladder (multiple indications) Cartilage Skin Others: Penis Testis Uterus