Commercial Applications of Stem Cells: NIH Lecture 06 Oct 2010
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My presentation today at a week long NIH class on Stem Cells: "Commercial Applications of Stem Cells "
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Commercial Applications of Stem Cells: NIH Lecture 06 Oct 2010
- 1. Commercial Applications of Stem Cells NIH Workshop Lecture Bethesda, Md Oct 6th, 2010 By: Jim Hardy President & CSO HemaCell Perfusion, Inc.
- 2. Background Wittenberg University University of Rochester BRL/Life Technologies, Inc. BP Solar In Vitro Technologies LavaAmp & Hemacell Perfusion @ FITCI
- 3. Stem Cell Market Projections and Time Line RegMed 2.0 USD (millions) 1961: Canadians Jim Till & Ernest McCulloch prove the existence of stem cells (Nature 1963) 1978: Hematopoietic SC discovered in UCB 1981: mouse ES cells isolated 1988: HSC isolated from blood 1992: Adult neural SC discovered 1994: first Cancer SC discovered 1996: Dolly the Sheep 1998: first human ES line
- 4. The Gartner “Hype Cycle” http://en.wikipedia.org/wiki/File:Gartner_Hype_Cycle.svg
- 5. Commercial Applications of Stem Cells
- 6. Picks and Shovels Tissue sourcing, collection, isolation and banking Cell Culture medium, Growth factors, cytokines, ECM proteins The challenges of ex vivo expansion QC Testing, characterization Stem cells in Drug Discovery
- 7. Tissue sourcing, collection, isolation and banking
- 8. Tissue sourcing, collection, isolation and banking
- 9. Tissue sourcing, collection, isolation and banking Accredited Tissue Banks Whole Organs-Transplant grade Surgical resection Birthing centers, mid-wives Live donor, bone-marrow, blood collection
- 10. Tissue sourcing, collection, isolation and banking
- 11. Tissue sourcing, collection, isolation and banking Density Gradient centrifugation
- 12. Tissue sourcing, collection, isolation and banking Immuno magnetic separation http://www.miltenyibiotec.com/Stemcell/NN_736_MACS_Cell_Separation_the_principle_1.aspx#1
- 13. Tissue sourcing, collection, isolation and banking Cell Sorting by Flow cytometry
- 14. Tissue sourcing, collection, isolation and banking Vita34, Leipzig DE http://www.vita34.de/vita/en/laboratory.php?navanchor=2110006
- 15. Cell Culture medium, Growth factors, cytokines, ECM proteins 26.2 mM Na Bicarbonate 21 mM HEPES 2.2 mM Fructose 2 mg/mL BSA 10.7 g/mL L-Alanine (free base) 18.0 g/mL L-Asparagine –H2O 16.0 g/mL L-Aspartic Acid 17.6 g/mL L-Glutamic Acid 9.0 g/mLGlycine 13.8 g/mL L-Proline 12.6 g/mL L-Serine 135 fM Insulin 2.4 M hydrocortisone 10 % (v/v) serum Antibiotic Mix: 2.04 % (v/v) Pen-Strep 0.05 mg/mL Gentamicin 0.05 mg/mL Amikacin 0.20 % (v/v) Fungizone
- 16. Cell Culture medium, Growth factors, cytokines, ECM proteins
- 17. The challenges of ex vivo expansion
- 18. The challenges of ex vivo expansion
- 19. The challenges of ex vivo expansion
- 21. Flow cytometry
- 22. Differentiation and function
- 23. Proteomics
- 25. Stem cells in Drug Discovery As a replacement for Primary Cells Skin: Wound healing & absorption models Bone, cartilage Hepatocytes Renal cells Circulatory Cardiomyocytes Neurons Pulmonary cells In vitro models for metabolic homeostasis & Organogenesis Demonstrate a “stimulation” of injury & repair mechanisms Inhibition of necrosis/apoptosis Tissue specific developmental pathways Cancer Stem Cells
- 26. Alzheimer's Disease and neurodegeneration: The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration, BMC Neurosci. 2006; 7(Suppl 1): S2.
- 27. Some of the Players
- 28. The future?
- 29. Conclusions A business can be built around manufacturing almost any of the tools for Stem Cell research which precedes clinical testing. Stem Cell research holds the promise of a new era in medicine, a Gold Rush of sorts. Before any EUREKA moment, researchers are going to need picks and shovels to find the Gold. In other words, before the FDA approves the use of manipulated cells for therapeutic purposes, investigators will need to completely understand the systems they’re working with .
Notas del editor
- One“trigger” event was Dolly the Sheep in ‘96. Another was the “discovery” of iPS cells only a few years ago.
- There are still a few clinical applications today. The primary source of transplantable material is Bone Marrow derived HSC. We need to do a lot of research before we strike it rich. We need to tools to find the gold.The business plan is analogous to being a “Hardware store” in a Gold mining town
- So we’re going to discuss some of the tools of the trade, the picks and shovels and the commerce around them.I should add some of my personal bias, to be fair. My work and background is with Human Adult Stem Cells, so that is my focus. Specifically, I am focused on using whole afterbirth, not just the Cord Blood and Placental blood, but the whole organ: cord, amnion, and placental tissue as well as the blood components.Keep in mind that there are parallel paths, often more advanced, in non-human and veterinary model systems. There are also a number of areas, ex vivo expansion for example, that are much more detail for ES cells than adult cells.
- The “grave diggers” and unethical morticians get a lot of press and attention and the damage these criminals do goes far beyond the corpses they’ve desecrated. It has perpetrated a myth that all stem cell research is illegal. That tissue banking is an unethical practice.There is a huge business in collecting tissues for organ transplantation and in performing transplants. But not all tissue consented for transplant can be matched with a suitable recipient. I like to think that research use fills a void for the grieving family, hoping make some good from their loss.The Organ and Tissue Act set conditions for tissue collection and the necessity of “informed consent.” GTP (Good Tissue Practices) analogous to GMP, regulates the storage and “quality” of tissues used in clinical applications.But any organ/tissue being used to isolate stem cells needs to be fresh, viable and free of contamination.And like I said, I am not an ES practitioner, so I am not raid IVF clinics waiting for cast offs, but I ask: what is wrong with saving these fertilized eggs from the autoclave and using them to save humanity from unnecessary pain and suffering?
- Most OPOs and Tissue banks are “Non-Profits”, but this does not mean they’re not generating commerce and revenue and paying a lot of salaries. They serve a necessary a valuable purpose that is really just starting to be realized.
- Look at this partial list of Accredited Tissue BanksSurgical resection includes adipose tissue from “tummy tucks” cosmetic surgery, cancerous tumors, normal tissue adjacent to a tumor in large organs like liver, brain and skin.
- A typical Cord Blood collection kitDiscuss costs and benefit. Public Cord banking is the way to go. Save the Afterbirth!!DIY Regenerative Medicine, Open ScienceMediStem ‘s regenerative endometrial cells.“Your Monthly Miracle”
- Density Gradient sedimentation or centrifugation is the simplest, most broadly used preparative technique. Ficoll, Percoll, Lymphocyte separation medium, Hetastarch. Many examples from at least a dozen different sources.Minimal manipulation to keep within the GTP and not have to deal with more rigorous “GMP” regulations.
- Miltenyi,LifeTech (Dynal beads), Stem Cell Technologies RoboSep
- Overview of technologyWaters, BD, Coulter flow cytometers costs, reagents, disposables
- And everything, virtually, has to be stored. Takes people, and computers and logistics, inventory control. And how much do you think each one of those MVE’s costs? And How much LN2 does it take to keep them full? Note the Controlled rate freezers. This is commerce. Manufacturing.
- This is an area I am not going to go into a great level of detail, but these tools, picks and shovels, are perhaps some of the most important and some of the most versatile tools for the Stem Cell researcher. And believe me, you don ‘t want to see a Cell Culture guy out there bleeding goats to make their own antibodies.But look at the complexity of something as simple as DMEM. Still mostly bottled water.
- Most involve the use of antibodies and expensive equipment.
- chemical signals (polypeptide growth factors and cytokines) in the local tissue environment control growth and specialization of different cell types of the prostate, the liver, the vascular system and neural tissue. These signals determine the normal development and function of the tissues while aberrations result in tissue dysfunction and diseases, such as cancer, stroke, atherosclerosis, liver, and neural disease. These signaling systems which are comprised of a signal polypeptide from one cell type and a reception system on another are the basis for communication among cells in tissues, but also serve as sensors of signals like hormones and nutrients that come from outside the tissues. The cellular reception system for many signal polypeptides consists of a transmembrane protein whose external domain interacts with signal polypeptides and an intracellular domain which is a protein kinase enzyme which activates metabolic pathways that control cell growth, function, and gene expression.
- NFT = neurofibrillary tanglestrkA = tyrosine kinaseThus, the phenomenon of apoptosis, that is central to the Neurotrophic Factor Hypothesis, was first observed in the context of the discovery of NGF and its role on differentiation and survival of sympathetic and sensory neurons of the peripheral nervous system [70,71]. During development, neurotrophins regulate neuronal survival and differentiation, and determine the pattern of innervation and the expression of proteins that are crucial to a specific neuronal phenotype, like neurotransmitters and neuropeptides, neurotransmitter receptors and ion channels. According to the neurotrophic hypothesis, the correct pattern of innervation is dependent upon competition of developing neurons for a limited supply of growth factors secreted by target tissues, thus ensuring a balance between the number of neurons and the size of the innervated targetexcitotoxicitydue to overactivation of glutamate receptors represents a final common pathway for both acute neurological disorders, such as stroke, trauma and epileptic seizures, and chronic neurodegenerations like AD