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The Historical Evolution From Embryonic Stem Cell Research to Commercial Cell Therapy By

The Historical Evolution From Embryonic Stem Cell Research to Commercial Cell Therapy By Prof. Morsi Arab University of Alexandria. IN GENE THERAPY We aim to generate a source of cells which can secrete insulin in response to glucose.

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The Historical Evolution From Embryonic Stem Cell Research to Commercial Cell Therapy By

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  1. The Historical Evolution From Embryonic Stem Cell Research to Commercial Cell Therapy By Prof. Morsi Arab University of Alexandria

  2. IN GENE THERAPY We aim to generate a source of cells which can secrete insulin in response to glucose. .

  3. B- cells express two specialized proteins important for the glucose sensoring:-I - Glucose Transporter(GLUT2).II - Glucose phosphorylating Enzyme (Glucokinase ) .

  4. Sources for Production of Genetic B- Cells I- Mature B- cells : - Allogenic - Xenogenic II- B-cell Precursors, including Stem Cells. III- Genetically engineered Non B-Cells (e.g. Hepatic )

  5. The mature B-cells as a source are : Limited in number. - Have very limitedproliferation capacity. - Stimulating their growth by growth factors diminishes theirsecretory power.

  6. Stem Cells are clonogenic cells capable of Self renewal and multilineage differentiation. • So , they can be expanded in vitro and in vivo. • Stem Cells are : * Totipotent * Pluripotent * Multipotent

  7. Sources of Stem Cells (SC): 1- Embryonic Stem Cells *(ethical problems) 2- Embryonicgerm cells. *(ethical problems) 3- Embryonic Carcinoma cells (?) 4- Adult stem cells avoids the ethical dilemma can allow auto transplantation

  8. Advantage of developing B-cells from Stem Cells ? The Stem Cell has * high capacity togrowandproliferate * but limited capacity toproduceinsulin.

  9. : Stages of Beta cell development and differentiation - Fetal Entoderm. cell ( high growth potentiality)  - Panc. Duct epith. Cell  - Committed Endoc. precursor cell  - Growth Stimulated B-cell  - Mature B- cell (V. low division capacity)

  10. During Differentiation of Embryonic Stem Cells (ESC) to insulin Secreting StructureThree Observations :1- The endoc. Panc. Cells exist in clusters of 4 types of cells organized in stereotypical topology. 2- They develop in close contact with neurons… [ similar mechanisms control development of Endocrine and CNS systems …!!!]. 3- An early step in neural differentiation of ESC is generation of cells expressing NESTIN.

  11. NESTIN- Nestin is an intermediate filament protein normally found in neural precursor cells . - It is also identified in immature pancreatic cells which upon differentiation in vitro give rise to insulin andglucagon producing cells .

  12. Steps for experimental bioengineering of Insulin expressing cells from Embryonic stem cells include:1- Production of enriched population of Nestin +ve cells 2- Selection 3- Expansion , and 4- DifferentiationHow: : By using different media to suppress othercells and Fibroblasts to provide GrowthFactors,Transcription Factors with supplements of Nicotinamide , etc

  13. . ============================ In order to achieve : I- growth . II- differentiation. III- secretion of insulin in response to glucose.

  14. Testing the potentials of the islet-like clusters to survive and function in vitro : (when grafted(subcut) in diabetic mice ) 1- implanted cells vascularize ,and 2- remain immuno-reactive to insulin (i.e. continue to expressinsulin ) . 3- form aggregates similar morphologically to normal pancreatic islets .

  15. A New Source of Stem Cells From Umbilical Cord Blood Available for collection at child birth and storage for future use for the same child . Currently, only few clinical diseases : heart disease , spinal cord lesions, leukemia , diabetes…? but with potential increases in the future. (Statistically: 5-37/1000 ), is it worth to be a routine ….?

  16. Umbilical Cord Stem Cells : Collection and Storage (cont. ) * Special advantages over bone marrowtransplant: immediately available - genetically identical - no risk of rejection or infection . * Specially recommended with family history of genetic diseases which are treatable by stem cells. • In USA:private stem cell storage banks. In UK: storage is still debatable. But Donations of stem cells from Cord blood is established.

  17. Thank You

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