Stem Cells:

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

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■ Why it is Important?

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■ 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)

Oocyte Somatic Cell Nuclear Transfer (SCNT) Sperm Fertilized Egg/Zygote Blastocyst 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

- 0.01-0.001% of Bone marrow cells - Has

Immunomodulaory

properties -

Animal study:

BMT (GVHD ↓ ) Skin graft, -

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

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