Stem Cells: Roadmap to the clinic Negar Azarpira, MD Associate professor of Pathology 14 April 2010

■■■■ Why it is Important? ■■■■■■■■ Is It As A New Drug?

Stem cell Definition Unspecialized cells in human body that are capable of becoming specialized cells, with new specialized cell function. Very broadly, they divided in two major groups: Embryonal/Fetal SC Adult SC Best example: Hematopoietic stem cells (HSC)

Sources of Human Stem Cells

Embryonal / Fetal Stem Cells

Embryonic Stem Cells (ESC)

Somatic Cell Nuclear Transfer (SCNT) Blastocyst Oocyte Fertilized Egg/ZygoteSperm Adult/Somatic Cell Replace with Nucleus From Donor Adult Cell SCNT Blastocyst

Morphology Embryonal Stem cells

Advantages -Unlimited self renewal -Commercially Cell lines -Pleuripotent -High Telomerase activity & Low chromosomal instability

Clinical Application Transplantation of differentiated cells Pharmaceutical screening Study oh development & congenital anomaly

Adult Stem cell

Hematopoietic stem cell Cell surface marker/ Florescent or magnet

Hematopoietic stem cell CD34 + : 0.5-5% of Bone marrow

Hematopoietic Stem Cell Transplantation Outologus or Allogenic HLA matching ■ Source of Hematopoietic cells: Bone marrow (GM-CSF,…) Mobilized peripheral blood Umbilical cord blood

Graft versus Host Disease (liver, Intestine, mucosa) Graft versus Tumor

Clinical Application Treatment of hematological malignancy Inherited disease (SCID), β Thalasemia Mediate tolerance for Solid organ allograft Vehicle for gene Transfer

Future Direction…. ↓ 1. Genetic modification (addition of genes for self renewal, Wnt) 2. Three Dimensional stromal culture 3.Supportive endothelial population or cytokines

Other interesting cells in bone marrow CD133 + : Endothelial precuresure Mesenchymal cell The most common phenotypical markers: CD90, CD73, and CD105

Mesenchymal stem cells % of Bone marrow cells - Has Immunomodulaory properties -Animal study: Skin graft, BMT (GVHD ↓ ) - Human study: Bone marrow graft Crohn’s disease Islet cell transplant

First Stem Cell Drug Prochymal Prochymal is a preparation of mesenchymal stem cells, obtained from the bone marrow of healthy young adults The first SC product approved by the FDA as pharmaceutical product The target disorders of this therapeutic are GVHD and Crohn’s disease For the repair of heart tissue following a heart attack For protection of pancreatic islet cells in patients with type I diabetes For the treatment of Chronic Obstructive Pulmonary Disease (COPD) Osiris Therapeutics, Inc

Reprogramming induced pleuripotent stem cell (iPS) By ectopic expression of transcription factors by retroviral transduction can reprogram somatic nuclei to the pleuripotent state.

In the future…. With Tissue Engineering & Regenerative Medicine: Can Help patients with Stroke, Myocardial infarction, Cord injury, Diabetes, Cirrhosis, Parkinson…

Bioethics

Reference Stem cell from bench to bedside Bongso A & Lee E.H 2005

Thank you for your attention.. Thank you for your attention