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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)
Oocyte
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■
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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
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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: 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..