2. WHAT are stem cells and WHERE do we find them??

3. Cells are complex with lots of moving parts.

4. Stem Cells have the capacity to become any cell in the body

5. This means they have
multiple potential to give rise to any tissue in the body.
The term for this is:
Pluripotent.

7. The instruction manual “transcribes” the legos into specific sheps

8. The DNA transcribes stem cells into specific lineages, or tissue

9. There are four types of pluripotent stem cells:
Embryonic*
Nuclear transplant*
Parthenote*
Induced
*Requires a human egg to create.
Parthenote = activation of an egg w/o sperm (parthenogenesis)

10. Embryonic Stem Cells: Potential to Generate All Tissue Types
Concerns: Ethical Issues and Restricted Federal Funding

11. Nuclear Transplant

12. Activation without sperm

13. Induced Pluripotent Stem Cells (iPS)
Remember ME…
Viral vectors – UBER for viruses
We now use messenger RNA to carry genetic reprogramming transcribers
Stem Cell-based “Personalized Medicine” 13

14. Areas of Focus Universal Blood Supply Viral Antibodies
Restoring Vision
Repairing Damaged Heart Tissue
Inherited Skin Disease
Bone and Cartilage Regeneration
Stopping Cancer at Its Source
More efficient/safe method for reprogramming adult skin cells into
Induced Pluripotent Stem (iPS) Cells

15. Cancer Patients
Why?
Regeneration vs Killing! Increased understanding of MCDB helps us treat and hopefully one day prevent cancer.

16. Cancer Stem Cell Theory
Cancer stem cells
Tumor growth
Tumor
No tumor

17. Cancer stem cells: are we missing the target?
Therapies directed against rapidly dividing cells
Tumor with stem cells
Cancer stem cells survive
Tumors recur
Therapies directed against cancer stem cells
Tumors regress
and never recur
Tumor with stem cells
Cancer stem cells killed

19. Induced Pluripotent Stem Cells (iPS)
Remember ME…
Viral vectors – UBER for viruses
We now use messenger RNA to carry genetic reprogramming transcribers
Stem Cell-based “Personalized Medicine” 19

20. Asymmetric Division observed for First Time!
Cancer stem cells
Tumor growth
ASYMETRIC DIVISION allows stemness and rapid tumor generation
Like discovering Bigfoot…
Tumor
No tumor

21. Cancer Stem Cells HIJACK SOX2!!!
SOX2 transcribes enough of the cell’s genetic makeup to clone itself AND remain stemlike
Asymetric division
Now that we know this, it spells trouble for the cancer stem cells

22. Cancer Stem Cell Theory
Cancer stem cells
Tumor growth
BUSTED!
Tumor
No tumor

23. Generating humanized mouse models to treat cancer.

24. Generating humanized mouse models to treat cancer.

25. IMMUNOTHERAPIES

26. Cancer Signaling Pathways
Cancer signaling is not linear. It is a highly inter-connected and redundant network

28. Pathway Inhibition
Inhibitor blockades

29. Pathway Deregulation

30. Decreasing Pathway Congestion
-Decreasing the stroma
-Really what this is about isn’t removing traffic or congestion, but decreasing the stroma that contains the vitals, such as food, electricity, etc.
SORT OF…

31. DECREASING STROMA
TEM = tumor markers, or bulls’ eyes!
Blood vessels = utilities
Fibroblasts = steel frame
MSC = bolts, cables and welds

32. CAR T-Cell Therapy
 CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells
Antigen - a toxin or other foreign substance that induces an immune response in the body, especially the production of antibodies.
-Right-sizing radiation to make standard care more effective
-Better ways to test CAR Ts so that we can understand better how to reeducate them

34. CAR T-Cell Therapy
 CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells
Guard analogy – can’t come thru the door, so the police send someone thru the vents…
Antigen - a toxin or other foreign substance that induces an immune response in the body, especially the production of antibodies.
-Right-sizing radiation to make standard care more effective
-Better ways to test CAR Ts so that we can understand better how to reeducate them

35. Immunomodulatory Polymeric Delivery
Bioengineering
Immunology

36. Nanoparticles and Polymers delivering genetic immunomodulation into the Tumor Microenvironment
This is an example of how we might debulk the tumor or simply target its infrastructure / life support systems

37. Allogeneic Antibodies as a Cancer Immunotherapy
Donor
Recipient
GVHD
What we know… ?
What we wonder…

38. Thank you!

39. Curing Skin Disease In collaboration with
The Epidermolysis Bullosa Center of Excellence
The Children's Hospital Colorado

40. The Therapeutic Potential of Induced Pluripotent Stem (iPS) Cells
Patients with
Inherited Skin Diseases
Collect skin cells
Reprogram into iPS cells by
non-genetic methods
Genetically identical iPS cells
Expand and store
Genetic correction of mutation
Differentiate into keratinocyte stem cells
Return to patient as a graft

42. Healing the Growth Plate