Getting Started with Alphagenix                     Steve is an advisor, collaborator and friend. He has the innate ability to bring his his scientific expertise and entrepreneural insticts together in a way that anticipates emerging needs of the research community we both serve. He is an expert in immunology, neuroscience, virology and regenerative medicine (stem cells).  Most notably, he is the sole inventor on the patent that formed the basis for using the Nodaviruses as vaccine and gene therapy vectors U.S. Patent 6,171,591. These vaccines are in various stages of preclinical development as are protoype therapeutic vaccines for neurodegenerative diseases.  Our two companies first worked together to identify and manufacture several important stem cell markers. We tested potency on our STEMEZ hNP1TM Human Neural Progenitors. They proved to effective. This confirmed Steve’s ability to identify, design and make these markers. The demand for them continues to grow. These successes were a prelude of good things to come. Current Focus Steve is currently  developing novel products and technologies for basic and clinical research with a particular emphasis on stem cell markers, biomaterials and regenerative medicine. The biomaterials product focus involves the design and application of 3-dimensional biomaterials comprised of extracellular matrix components and peptide nanofibers that have cell culture and tissue engineering applications. In addition, the company conducts regenerative medicine research that involves basic science and translational preclinical research using stem cell regulatory network discoveries and novel preclinical studies utilizing animal models with a focus on neurological disease and diabetes. He is a contributor to: Stem Cell Therapy for Neurological Diseases Stem cell therapy for the treatment of acute and chronic neurological diseases

2001-Present-President-Alphagenix 2006-2007-CSO-Neuromics 2000-2001-President-AmProx, Inc 1996-2004-President and CSO-Pentamer Pharmaceuticals 1996-1997-Sr. Research Fellow-Medical Biology Institute. 1995-1997-Research Associate-Scripps Research Institute 1995 PhD Purdue University Musashi-1 Antibody Image: Musashi (green) staining of neural rosettes(human). Nuclei are counterstained blue (DAPI). Image courtesy of Dr. Steve Stice and Dr. Patricia Wilson, University of Georgia.

Harting, Matthew T., Cox, Charles S. and Hall, Stephen G.  Adult Stem Cell Therapy for Neurological Disease: Preclinical evidence for cellular therapy as a treatment for neurological disease. In Vemore and Vinoglo (eds): Regulatory Networks in Stem Cells. Humana Press, pp 561-573, (2009). More information.

Specific Projects

1. Steve has 3 major projects underway:
   In collaboration with Dr.  Charles Cox , Distinguished Professor, UT Medical School @ Houston, Steve has been using stem cells to treat  Traumtaic Brain Injury (TBI) in Rat. Neural stem cells transplanted into the site of injury. In this model, treated rats showed injury significantly improved motor skills with a moderate recovery in cognitive ability. This research forms the base for eventually repairing damage in humans suffering TBI. Methods and reagents developed also could be useful for basic research and drug discovery.
2. Steve is working with Burnham Institute to develop methods for using  Human Mesenchymal Stem Cells to regenerate beta cells. This research holds promise for type 1 diabetics.
3. Steve developing biomaterials including extracellular matrix proteins in novel cell culture systems and synthetic peptide nanofibers for these purposes.  It is investigating stem cells and genetically engineered cells and their interaction with these biomaterials, which has the ability to increase the efficacy of cell therapy. This is highlighted by a human laminin sytem that shows promise in restoring function in Muscular Dystophry.

The last project is promising enough that it could lead to funding for phase 1 testing.

I will continue to keep you posted on progress. I am excited about the new regeants and method that evolve from Steve’s Research. As these prove to work in unique and novel ways, the will become available to Neuromics.

STEMEZ hN2 Primary Human Neurons

I have profiled Steve Stice’s research here. The focus has been the excellent research results he and his team at ArunA Biomedical have generated with STEMEZ(TM) hN2 Human Neurons and hNP1 Human Neural Progenitors.

The story continues. He will be presenting the latest at the 9th Annual World Pharmaceutical Congress in Philadelphia, June 14. Topics include: using these neural cell lines to study neurotoxicity in cell-based assays and disease modeling.  Recent work conducted in outside laboratories demonstrates that these lines are more sensitive to environmental toxicants than traditional cellular models.

Sample high throughput assay applications:

• Cell morphology and neurite outgrowth
• Cell signaling and transcription factor expression
• Receptor and ion channel function
• Cytotoxicity
• Apoptosis, genotoxicity and DNA damage

These capabilities has been confirmed by our customers. I look for the use of the STEMEZ cell lines to continue to grow as researchers discover their value in Drug Discovery and Basic Neuroscience capabilities.

Dr. Steve Hall

Dr Steve Hall has been a friend, collaborator and mentor since I purchased Neuromics. This includes being a Neuromics’ Premier supplier of Stem Cells and Related Markers, Media and Methods. Steve is currently President at AlphaGenix, Inc.

His expertise includes developing novel products and technologies for basic and clinical research with a particular emphasis on stem cell markers, biomaterials and regenerative medicine. The biomaterials product focus involves the design and application of 3-dimensional biomaterials comprised of extracellular matrix components and peptide nanofibers that have cell culture and tissue engineering applications. In addition, the company conducts regenerative medicine research that involves basic science and translational preclinical research using stem cell regulatory network discoveries and novel preclinical studies utilizing animal models with a focus on neurological disease.

He is a contributor to: Stem Cell Therapy for Neurological Diseases Stem cell therapy for the treatment of acute and chronic neurological diseases

Harting, Matthew T., Cox, Charles S. and Hall, Stephen G.  Adult Stem Cell Therapy for Neurological Disease: Preclinical evidence for cellular therapy as a treatment for neurological disease. In Vemore and Vinoglo (eds): Regulatory Networks in Stem Cells. Humana Press, pp 561-573, (2009). More information.

Stay tuned for Steve’s backstory in June!

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Drilling down further, I am pleased to present Electro-physiology and related data generated by Aruna and collaborators: hN2 Cells-Electro Phys Data Supplement

hN2-Whole Cell Voltage Clamp

Figure. hN2 cells can produce inward currents that generate action potentials. (A) Isolated hN2 with significant neurite growth 1 week  after plating . This cell was subjected to whole cell voltage clamp utilizing a potassium gluconate based intracellular solution. (B) Voltage gated inward and outward currents were elicited from this cell with depolarizing voltage steps. (C) Inward currents from another cell (potassium gluconate intracellular) were abolished by local application of 1 µM tetrodotoxin (red trace) while outward currents remained. Inward current recovered as TTX washed out of the region (green trace). (D) A different cell which exhibited voltage activated inward currents that inactivated in response to a 50 ms prepulse at different membrane potentials. The experiment was done 27 days after the removal of bFGF. A cesium gluconate based intracellular solution was used for this experiment to block outward potassium currents. The membrane potential for half maximal inactivation by standard Boltzman fitting (red line) was -40.1 mV with a slope of 4.7. (E) Recovery from fast inactivation utilizing a paired pulse protocol in the same cell as C. The single exponential time constant for recovery of inactivation was 1.7 ms (red line). (F) A different cell which elicited an overshooting action potential upon current injection under whole cell current clamp utilizing a potassium gluconate based intracellular solution. Inset: Response of the same cell under voltage clamp to a change in membrane potential from -80 mV to -10 mV elicited a peak current of 457 pA. Scale bars for inset: 5 ms, 0.2 nA.

We are in the process of finalizing details for distributing their human neuron cultures. Here is the related press release:

Here they isolate, and maintain in culture, neural progenitors demonstrating properties of these neural epithelial cells from WA09 human embryonic stem cells (hESCs):

D.W. Machacek, S. K. Dhara, C. Sturkie, K. Hasneen, D. Carter, L. Murrah Hanson, P.R. MacLeish, M. Benveniste, S.L. Stice. DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELL DERIVED NEURAL PROGENITORS INTO FUNCTIONALLY RESPONSIVE POPULATIONS IN THE ABSENCE OF EXOGENOUS EGF.

On September 5th, Updated Guidelines for Stem Cell Research was released by the National Academies.

One reason for the 2008 modifications is to provide guidance on the derivation and use of new human stem cells that were first developed last year.  These cells — called “induced pluripotent cells” — are made by reprogramming nonembryonic adult cells into a stem-cell-like state, in which they can be manipulated to form a wide array of specialized body cells.  Although induced pluripotent stem cells can be derived without using embryos, the ethical and policy concerns related to their potential uses are similar to those pertaining to human embryonic stem cells.  For example, issues arising from mixing human and animal cells in a single organism are relevant for stem cells from both embryonic and nonembryonic sources.  However, derivation of induced pluripotent stem cells does not require special stem cell expertise and is adequately covered by current Institutional Review Board regulations, the report says.

Copies of 2008 Amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research are available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at http://www.nap.edu

I did want to highlight yet another potential application for stem cells. For this, we send kudos to Dr. Yan Xu and his colleagues at University of Pittburgh for their findings on inflammatory response in Golbal Ischemia. Their work was recently published:

Aaron Hirko, Renee Dallasen, Sachiko Jomura, Yan Xu. Modulation of Inflammatory Responses after Global Ischemia by Transplanted Umbilical-Cord Matrix Stem Cells. Stem Cells First published online August 21, 2008; doi:doi:10.1634/stemcells.2008-0075

Secondary to Cardiac Arrest is Brain Damage do to lack of blood flow. This is marked by a delayed loss of Neurons in CA1 hippocampus region of the brain due to inflammatory response.

The story timeline of this response is good then bad with interesting twists. The delay in neuronal loss is linked to initial inflammation. It involves both reactive astrocytes (astrocytosis) and glia. Delaying the loss is, of course, good.

…But then, the reactive astrocytosis and related glial scarring cause a physical and biochemical barrier to regeneration of neurons…a bad thing. Protecting the microglia is a good thing, because they these cells serve as scavengers for clearing the cellular debris. They can also secrete a variety of cytotoxic and protective chemicals.

The wow factor in this research is that  implanted rat umbilical-cord matrix (RUCM) cells can provide partial protection against neuronal injury in rat brains. Rats treated with RUCM cells three days prior to an 8-min CA had only 25-32% neuronal loss in the hippocampal CA1 region compared to the typical 50-68% neuronal loss observed in the untreated or the vehicle-treated animals. This could be due to to the favaorable modulation of the “good-bad” inflammatory response.

The good news in the search for therapies for stroke and cardiac arrest victims is combined, stem-cell-like RUCM cells offer protection against neuronal injury after global cerebral ischemia by enhancing the survivability of the astroglia in the selectively vulnerable regions.

We are pleased that the research team used our GFAP antibody as an marker for astrotytic in their studies.

Dr Steve Stice and Human Stem Cells

I am pleased and honored for the privilege of profiling Dr. Steve Stice.  He has a history of working in areas that are Biotechnology Headliners…from cloning to stem cells. Here I will be focusing on his current work with Human Stem Cells and Neural Progenitors  at ArunA Biomedical and The University of Georgia. As with all the News Behind the Neuroscience News, I will highlight how it could impact Neuroscience Research and Drug Discovery.

The Back Story

Where it Starts

About Dr. Steve Stice

Dr. Steve Stice is CSO of Aruna Biomedical Inc and a Professor and Director of the Regenerative Bioscience Center and has a Georgia Research Alliance Eminent Scholar endowed chair.

Prior to joining the University of Georgia, Dr. Stice was a cofounder and Chief Scientific Officer at Advanced Cell Technology, a stem cell company.  Throughout his career he has published and lectured internationally on the topics of cloning and stem cells. 

In 2001, three of the human embryonic stem cell lines that Dr Stice’s lab derived were approved for federal funding by President Bush. In 2006, he was appointed by Gov. Perdue to the Post Natal Cord Blood Commission for the state of Georgia.

Dr. Stice founded Aruna Biomedical, Inc., and in cooperation with Millipore Inc. was first group to market a product derived from human embryonic stem cells (2007). The product is a neural stem cell used for research on neurological diseases and disorders, ranging from Parkinson’s disease to depression.

Contact Information:

sstice@arunabiomedical.com

Current Products

There is good news. Neuroscientists can now easily and inexpensively get human neural progenitor cells for Drug Discovery, Toxicity and Basic Research.

ENStem-A ™, Neural Progenitor Expansion Kit
hN2™, ArunA Human Neural Cell Kit 

So what was once difficult and frustrating, is now easy and convenient. Buy the kits and here’s an example of what you get.

What is Next

Knowing the needs and wants of the marketplace, ArunA’s products and capabilities excite me. Any tools that have they capabilities to bring researchers a steps closer to discovering cures for insidious Neuro-diseases need to be embraced. All of us have or will be touched by these diseases.

In my conversations with Steve, I am impressed with his clear understanding of how to evolve ArunA’s product to increase their value proposition. Available soon could be cultures developed to fit the niche needs of specific researrch areas like Parkinson’s, Pain’s and Alzheimer’s. I plan on communicating these evolutions here and at my company’s website @ www.neuromics.com.