Stem Cell Activators

Vitro Biopharma Receives Research Award for Innovative Research!

Vitro Biopharma Receives Frost & Sullivan Technology Innovation Leadership Award: 2014 Best Practices for Stem Cell Tools & Technology in North America

Golden, CO / ACCESSWIRE / July 9, 2014 / Vitro Diagnostics, Inc. (VODG), dba Vitro Biopharma, is pleased to announce receipt of a prestigious award from Frost & Sullivan. The award is based on independent analysis of competing companies’ commitment to innovation, commercial success, application diversity and fulfillment of unmet needs. Vitro Biopharma out-ranked competing firms in all areas evaluated.

Cecilia Van Cauwenberghe, industry analyst for Life Science/Biotech with Frost & Sullivan, noted, “The activation of endogenous stem cells to differentiate into specific cell types appears as an alternative to mitigate the significant remaining regulatory obstacles to adult stem cell transplantation in the United States. Vitro Biopharma is aligning its scheduled stages of clinical trials to test mobilization of endogenous stem cells in the treatment of traumatic brain injury and autism spectrum disorders (ASD), in which pre-clinical research strongly suggests the activation of certain biochemical pathways to increase proliferation, migration, and differentiation performance. Vitro Biopharma’s approach does not require stem cell transplantation, while providing a non-controversial, cost- and time-effective alternative to the current methodologies of competitors.” The full Award Statement is posted on our website.

Dr. Jim Musick, Vitro Biopharma’s president and CEO, said, “We are honored to receive this award from Frost & Sullivan, a premier organization dedicated to corporate growth and development, as well as business expansion. While embryonic stem cell research presents numerous ethical problems and has long been the subject of considerable debate, adult stem cells provide the benefits of embryonic stem cells without the problematic issues. A hallmark of embryonic stem cells is pluripotency, a capacity to develop into any cell in the body. While once thought to be exclusive to embryonic stem cells, it is now clear that adult stem cells may be converted to the functional equivalent of embryonic stem cells through methods that manipulate gene expression. These relatively straight-forward methods were developed and validated in several labs, including Vitro Biopharma. We are now also gaining understanding of the cellular signaling processes that activate adult stem cells, including MSCs, neural and muscle stem cells that reside within our bodies. This opens the possibility to elicit stem cell therapy without transplantation. There are also potential enhancements in mental and physical performance and anti-biological aging effects that have been demonstrated in animals. We look forward to expanding the power of stem cell activation to advancing medical treatments.”

Pete Shuster, a director of Vitro Biopharma and the CEO and founder of Neuromics, said, “Endogenous stem cell activation catalyzes the body’s natural healing processes. Proving this has been an integral part of our internally funded research. The ability to activate specific stem cell expansion, migration and differentiation pathways holds great promise for sufferers of traumatic brain injury and autism.”

“We are also encouraged by initial results treating autoimmune disease with natural stem cell activators. As previously reported, this initiative has generated revenue growth for Vitro Biopharma. Participating in TBI- and Autism-related trials would significantly accelerate this growth.”

“I consider this award a validation of our strategy and anticipate more good news to come as we continue to execute and improve this strategy.”

Dr. Valerie Hu-Autism Mother and Researcher

Unraveling complexities in search of potential treatments
I first became aware of Valerie’s Research when she called to explore how our eSC derived Human Neurons could be of value in her research. When I asked, “How do you plan on using the cells?” she gave me an overview of her fascinating research. She went on to tell me about the role her autistic son, Matthew 26, has played in her quest. This resonated with me because my Godson, Stefan 23 is autistic (see: http://www.trainmanandmom.com/).The purpose of this backstory is to give an overview of why her research is proving a key piece of the puzzle in understanding the biology of Autism. More importantly, given the lack of research funding, I am hopeful it opens the door to new sources like Microyza. These would enable those most impacted to have a direct way to participate.

Dr. Valerie Hu

Autism speaks and acts in riddles. This is the story of how Valerie is working to find the clues needed to solves these riddles.

Her Research Journey
Valerie has a bachelor’s degree in chemistry from the University of Hawaii (1972) and a PhD, also in chemistry, from Caltech (1978). She conducted postdoctoral research into membrane biochemistry and immunology at UCLA. She is currently a Professor of Biochemistry and Molecular Medicine at George Washington University in Washington, DC.

Her current research has required a leap from membrane biophysics to functional genomics. The intersecting theme is both disciplines involve complex molecular biology techniques and methods.

Functional genomics adds the challenge of analyzing the expression of genes that could play a role in disease or disorder and comparing them with the same genes expressed in normal or healthy phenotypes. Then an even bigger challenge is having the expertise and tools to discover the context of how these dysfunctional genes relate to one another.

In some of her early research, she found 4,000 genes appear to behave differently in a group of severely autistic people as compared with non-autistic controls—a startling number, considering the human genome comprises 20,000 to 25,000 genes (see: Searching for Autism’s Treatable Roots). But what is causing this large set of genes to behave differently from the norm?

By mapping the relationship between these genes and integrating gene expression profiles with DNA methylation data a picture emerged. This led to the discovery of a suspected master gene whose protein expression regulates the expression of many downstream genes known to play a role in Autism. This includes genes responsible for development of the central nervous system and the ongoing regulation of neurotransmitters.

A Master Gene Speaks-RORA
The gene Valerie and her team discovered as a suspect is the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha-see: http://www.fasebj.org/content/early/2010/04/07/fj.10-154484.full.pdf). They found the expression of this gene is reduced in autistic brain. So how can a reduction of one gene’s protein have such a profound impact?

As nuclear hormone receptor, RORA indeed has the capability of impairing the function of downstream genes. In fact, RORA can impact a lot of them. Further, RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. (see: http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0017116&representation=PDF). Note: This is a highly accessed article: > 11,000 people have already accessed this article.

By mapping the relationship between these genes and integrating gene expression profiles with DNA methylation data a picture emerged. This led to the discovery of a suspected master gene whose protein expression regulates the expression of many downstream genes known to play a role in Autism. This includes genes responsible for development of the central nervous system and the ongoing regulation of neurotransmitters.

She continues to learn more about the biology of RORA. Her recent publication (see: http://www.molecularautism.com/content/4/1/14) validates many of the transcriptional target genes of RORA.

Figure: Possible downstream consequences of deregulation of the six confirmed transcriptional targets of RORA

This shows that RORA sets off a critical mass of events leading to massive and variable disruption of gene expression. These events are ultimately manifested in the spectrum that marks Autism-impaired social and communication skills, repetitive behaviors, learning difficulties and sleeping disorders.

What’s Next?
These are breakthrough discoveries. Much more needs to be done. Some of the questions that need to be answered include: Can RORA be up regulated and how could this be done? Can RORA be dysregulated by hormone-like environmental pollutants leading to increased risk for Autism? What impact will alterations in RORA expression have on downstream genes? What are the best methods to regulate RORA…small molecule agonists? gene therapies? Cell based therapies? and so many more.

This research requires predictable and ongoing funding. Government funding is harder and harder to find. So many are impacted by children and adults with Austism, given this, I believe this research could be an ideal candidate for Crowd Funding.

Inflammatory Macrophages in ALS Spinal Cord

In my many conversation with Neuro-disease researchers, I often learn of discoveries that beg to be shared. I have been collaborating with Dr. Milan Fiala to explore how our hN2 Primary Human Neurons could be best used to study the role of inflammatory cytokines in amyotrophic lateral sclerosis (ALS). This would build on the excellent research he and his team are conducting at UCLA.

He shared with me that these inflammatory cytokines could be the bad actors in ALS. Specifically, in vitro, superoxide dismutase-1 (SOD-1) stimulates expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, through activation of cyclooxygenase-2 (COX-2) and caspase-1. Further, they have discovered The lipid mediator resolvin D1 (RvD1) inhibited IL-6 and TNF-α production in ALS macrophages with 1,100 times greater potency than its parent molecule docosahexaenoic acid. ALS peripheral blood mononuclear cells (PBMCs) showed increased transcription of inflammatory cytokines and chemokines at baseline and after stimulation by aggregated wild-type SOD-1, and these cytokines were down regulated by RvD1. Thus the neurons are impacted by macrophages expressing inflammatory cytokines. RvD1 strongly inhibits in ALS macrophages and PBMCs cytokine transcription and production. Resolvins offer a new approach to suppression of inflammatory activation in ALS. To learn more see: Guanghao Liu, Milan Fiala, Mathew T. Mizwicki, James Sayre, Larry Magpantay, Avi Siani, Michelle Mahanian, Madhuri Chattopadhyay, Antonio La Cava, and Martina Wiedau-Pazos. Neuronal phagocytosis by inflammatory macrophages in ALS spinal cord: inhibition of inflammation by resolvin D1.
Am J Neurodegener Dis. 2012;1(1):60-74.

Images: Co localization of TNF-a- and IL-6- expressing macrophages with caspase-3-and the chemokine RANTES (CCL5) – stained neurons in ALS and control spinal cords. Frozen sections of ALS and control lumbar spinal cord were stained with anti-NeuN (red), anti-CD68 (green), anti-caspase-3 (magenta) or anti-RANTES (magenta), and DAPI (blue) (Immunofluorescence microscopy (20X)). The experiment was repeated with 2 other ALS spinal cords and 2 other control spinal cords and yielded comparable results.
Photomicrographs are shown in 2 patients (A, B, C, D) and 2 controls (E, F). (A) Co
localization (yellow) of TNF-a-positive (magenta) and (CD68-positive, green) macrophages with NeuN–positive (red) neurons; (B) Co localization (yellow) of IL-6-positive (magenta) and CD68-positive (green) macrophages with NeuN–positive (red) neurons; (C) Co localization of macrophages (CD68-positive, green) with apoptotic, caspase-3-positive (magenta) and non-apoptotic (caspase-3-negative (red)) neurons. Eight neurons are impacted by macrophages; 3 neurons are caspase-3-positive (arrows) and 5 neurons are caspase-3- negative (asterisk); (D) Co localization of macrophages (yellow) with RANTES-positive (magenta) and CD 68-positive (green) macrophages with NeuN-positive (red) neurons. (E&F) No macrophages (green) are detected in 3 control spinal cords. (G&H) The table shows that in three ALS spinal cords 19.2 +/−4.8% NeuN-positive (red) neurons co localize with TNF-a -positive (magenta) macrophages (green) and 18.5 +/− 4.9 % NeuN-positive (red) neurons co localize with IL-6-positive (magenta) macrophages (green), whereas in control spinal cords 0% neurons (red) co localize with macrophages (green).

I will keep you posted on progress.

Nanofiber 3-D Cell Based Assays

This “News behind the News” is a historic event.  It demonstrates how nanofiber scaffolds can be used to engineer organs for human transplants. Good news for researchers looking solutions are in vivo like environments for cell based assays.

Nanofibers Solutions work in transplants-imagine how well they will work in your 3-D based cell based assays.

3-D Cell Based Assays for Drug Discovery are the future. Like any new model, adoption rates are a function of how well the new solutions works. “The proof is in the pudding”.

Here’re highlights of a historic event based on transplants using nanofiber engineered laryngotrachea : Collaboration between Nanofiber Solutions and the Karolinska Institutet produces first synthetic laryngotracheal implants seeded with the patient’s stem cells to be successfully transplanted into human patients in Russia.

COLUMBUS, Ohio, June 26, 2012 – Nanofiber Solutions, LLC, an Ohio-based developer, manufacturer and marketer of 3-D synthetic scaffolds to advance basic research, tissue engineering and regenerative medicine announced today the first and second successful transplants of its tissue engineered laryngotracheal implants seeded with cells from the patients’ bone marrow.

The surgeries were performed June 19th and 21st at the Krasnodar Regional Hospital (Russia) by Dr. Paolo Macchiarini, Professor of Regenerative Surgery at the Karolinska Institutet (Stockholm, Sweden), and colleagues. Dr. Macchiarini led an international team that included Dr. Vladimir Porhanov, head of Oncological and Thoracic Surgery at Kuban State Medical University (Russia), Dr. Jed Johnson, Nanofiber Solution’s Chief Technology Officer who created the synthetic organs, Harvard Bioscience (Boston, USA) who produced the bioreactor, and Dr. Alessandra Bianco at University of Rome, Tor Vergata, who performed mechanical testing during scaffold development.

Both patients, a 33 year-old mother from St. Petersburg and a 28 year-old man from Rostov-on-Don, were in au to accidents and suffered from a narrowing of the laryngotracheal junction for which they already had failed previous surgeries. Transplantation was the last option for the patients to have normal quality of life. Immediately following transplantation, both patients were able to speak and breathe normally.

Nanofiber Solutions, lead by Dr. Johnson, designed and built the nanofiber laryngotracheal scaffolds specifically to match the dimensions of each patient’s natural larynx and trachea, while Harvard Bioscience provided a bioreactor used to seed the scaffold with the patients’ own stem cells.  Although this procedure represents the world’s first and second successful use of synthetic synthetic laryngotracheal implants, it is Nanofiber Solution’s second and third successful organ implants using their synthetic scaffolds within the last year.

Nanofiber Solutions’ scaffolds mimic the body’s physical structure and allow for a more successful seeding, growth and differentiation of stem cells. Because the cells used to regenerate the larynx and trachea were the patients’ own, doctors report there has been no rejection of the transplants and the patients are not taking immunosuppressive drugs. (more).

Capabilities of 3-D nanofiber scaffolds for cell based assays:

Human brain tumor biopsy showing migrating tumor cells along the alligned nanofiber.
  • Nanofibers are optically transparent to allow for live-cell imaging and real time quantification of cell mobility using an inverted microscope
  • Nanofibers mimic the 3D topography found in vivo which produces a more realistic cellular response to therapeutics.
  • More realistic cellular behavior means you can use fewer animals and decrease time-to-market for drug discovery and development.
  • Nanofibers can easily be coated with ECM proteins using existing protocols for standard lab ware.
  • Cells can be easily removed for protein or gene analysis using trypsin, EDTA, etc.
  • We will continue posting relevant press releases, pubs and data that prove the capabilities of these important solutions.

    Dr. Jim Musick-Making MSCs Work

    Harnessing the Power of CellsTM

    Dr. Jim Musick

    Dr. Jim Musick

    Dr. Jim Musick and his company, Vitro Biopharma, give Basic and Drug Discovery Researchers the ability to harness the power of Human Mesenchymal Stem Cells (hMSCs). This power is essential for blazing new trails in the stem cell research and regenerative medicine frontier.

    I am pleased to welcome Jim as a partner in providing my company the expertise and knowledge highlighted in this profile. Together, we give our customers, colleagues and friends the ability to easily culture, grow, differentiate and maintain large stocks on hMSCs.

    Background

    Jim received his PhD from Northwestern University in 1975 and then joined the staff of University of Utah where he specialized in the study of Neuroscience and synaptic transmission. He joined UltraPure Laboratories in 1983.

    At UltraPure, he learned the art and science of commercializing biologicals. There he helped develop procedures for the commercial production of purified human pituitary hormones including, prolactin, growth hormone and TSH. This included developing QA/QC procedures to support commercial distribution of these products.

    He joined Vitro Diagnostics in 1988 and directed all operations involved in the establishment of a diagnostic product line that included about 30 different purified antigen products.  His direct responsibilities included research & development, manufacturing, intellectual property development and maintenance, marketing and sales.  He was also responsible for the development & initial commercialization of the fertility drug VITROPIN™ as well as the cell immortalization program of the Company.  He is an inventor or co-inventor of all issued and pending patents owned by the Company.

    In 1998 he also completed an Executive Program at JJ Kellogg Graduate School of Management, Northwestern University in Managing New Product Development.

    In 2000, he orchestrated the sale of the antigen manufacturing division to Aspen Biopharma (Nasdaq, APPY) while retaining IP related to use of FSH as a fertility drug and to cell line generation technology.

    He has the spirit of a polished scientist/entrepreneur with strong operational and process expertise.

    Harnessing the Power of hMSCs

    As President and CEO of Vito Biopharma, Jim leverages his expertise and experience to manufacture Cord Blood Derived hMSCs. The stem cell revolution demands large stocks of cells of the highest quality. Meeting the demand is the key to the development of stem cell related therapies. Vitro Biopharma has the capabilities to delivery.

    It is all about starting with vials of potent and pure hMSCs. From there, the customer can grow and differentiate large stocks and be confident in the quality because Jim’s company has the processes in place to insure this. The cell lines are well-characterized with regard to species authentication using sensitive PCR methods to quantify non-conserved genes including COX1, Cytochrome B and actin.  Vitro Biopharma also utilizes karyotyping to authenticate its  cell lines.  Adventitious agents are also tested negative by sensitive PCR methods including known viral contaminants and mycoplasma.  Performance is assured by rigorous testing of viability, growth rate and differentiation capacity for formation of chondrocytes, adipocytes and osteoblasts.  Finally these cells are characterized with regard to phenotypic cluster designation antigens.

    Current Products

    Native and fluorescent-labeled human MSCs including native and fluorescein/rhodamine-labeled MSC-derived chondrocytes and osteocytes along with MSC-GroTM  growth and differentiation media. MSC-Gro™ media is provided in low-serum, humanized and serum-free formulations for both growth and differentiation.  Humanized serum-free media may be supplemented with allogeneic or autologous serum for direct comparisons of growth and differentiation under these conditions.  Powdered MSC-Gro™ formulations are also provided.  Vitro Biopharma’s human MSCss have the capabilities to be expanded through at least 10 passages at rapid growth rates and can be further expanded to 16 passages (~50 population doublings) at slower growth rates.

    Human MSC-derived Osteoblasts stained with Alizarin red at 100 x.

    Image: Human MSC-derived Osteoblasts stained with Alizarin red at 100 x.

    Vitro Biopharma has recently launched a new and revised website complete with convenient online ordering and detailed product technical information (www.vitrobiopharma.com).

    Futures

    In our interview, Jim gave blinding glimpses of the future especially with regard to new products to extend Vitro Biopharma’s offering of clinical tools to fully explore the ever-expanding therapeutic applications of MSCs. I am excited about the potential. I will keep you posted as new products are commercialized.

    Gerry Shaw-Master of World Class Neuronal/Glial Markers

    Build it and They will Come

    Gerry and One of His Triumph's MCs
    Gerry and One of His Triumph’s MCs

    I am pleased to profile Dr. Gerry Shaw, a Professor at the University of Florida and also the Head of EnCor Biotechnology Inc.  His story is a guide for incubating and spinning out a successful biotech company (EnCor Biotechnology, Inc.) from a university research laboratory. It should provide an inspiration for fledgling entrepreneurs as the model required little capital investment and has enjoyed profitable growth.

    The Backstory

    Gerry’s major area of research interest can be summarized as the study of cellular changes resulting from central nervous system damage and disease states. These changes help neuroscience researchers understand the progression and hopefully discover root causes of diseases like Alzheimer’s, Parkinson’s and ALS. Understanding which proteins are involved in particular disease states also has the potential of identifying targets for therapies.

    The story starts with Gerry’s Post Doctoral research at the Max Planck Institute for Biophysical Chemistry in Goettingen, in what was at the time West Germany. Here he joined the world renowned laboratory of Klaus Weber and Mary Osborn. This lab had pioneering several important techniques, notably SDS-PAGE for protein analysis and the use of antibodies in immunocytochemistry. Later, after Gerry left the same lab made key contributions leading to the routine use of RNAi in “knock down” of normal cellular proteins. The lab had developed antibodies to tag the subunit proteins of microtubules, microfilaments, intermediate filaments and other cellular proteins, and then used these antibodies to visualize the proteins in immunofluorescence microscopy and on western blots. This enabled researchers to look at changes in the cellular expression of these proteins in powerful new way. These methods have become vital tools for understanding normal cellular function and what happens when cells transition from healthy to diseased states. This lab was an ideal location for Gerry to learn how to make quality monoclonal and polyclonal antibodies. Good antibody reagents are vital for the correct interpretation of immunofluorescence microscopy and western blots, and he was soon supplying his reagents to friends, collaborators and other researchers all around the world. Success is value as antibodies that do not as work as expected waste research time and resources, while quality reagents soon become appreciated and may get to be standard lab reagents.

    University of Florida

    The University of Florida, in Gainesville imported his expertise when Gerry joined the institute in 1986. Here he continued to make antibodies to Neurofilaments or NFs and other Neuronal-Glial Markers. It’s hard to keep a good thing a secret and Gerry faced growing demand from all over for these reagents. This proved a drain both financially and in terms of time commitment, as well as a significant conflict of interest with his basic biomedical research program.

    MAP2_Doering IHC Image: Co-culture of embryonic mouse hippocampal neurons and astrocytes. Primary embryonic hippocampal neurons at 7 days in vitro, were stained with Microtubule Associated Protein-2 (MAP, green) to enable the visualization of the dendritic arbors. These neurons were cultured on top of a monolayer of primary cortical astrocytes, stained with an antibody directed against

    Glial Fibrillary Acidic Protein (GFAP, red). The cell nuclei were visualized by staining with 4′,6-diamidino-2-phenylindole (DAPI, blue). BMC Image of the Month October 2010

    As a result Gerry took his first entrepreneurial step by selling his most popular reagents in bulk initially to Chemicon (now Millipore-Merck). Like any new business venture, he did not really know what to expect. It should come as no surprise that the reagents sold like hot cakes and the check started rolling in. Other immunoreagent companies approached Gerry and soon he was supplying antibodies to pretty much every major biotechnology vendor.

    ABC Biologicals to EnCor Biotechnology Inc.

    Success breeds success and as sales increased over the 1990s, it was time to form an independent business and so ABC Biologicals Inc. was incorporated in 1999 initially to buy equipment and develop licensing agreements. Since Gerry had income from sales, he was in the unusual and enviable position of not needing grants, investors, loans or cash from any other source, and so could proceed with almost total independence. The company was renamed EnCor Biotechnology Inc. in 2002, and at the same time moved into the Sid Martin Biotechnology Incubator, a lab dedicated to commercialization of intellectual property generated by the faculty of the University of Florida. The University of Florida is unusually experienced at this and is well known for launching Gatorade, Trusopt and many other products. After 4 years EnCor “graduated” from the Incubator and now occupies a facility in Gainesville. The company now has almost 100 products with many more under development. This is good news for the Neuroscience community.

    The EnCor-Neuromics Connection

    Neuromics provides EnCor Biotechnology reagents to researchers studying neuro-degeneration, neuro-regeneration, neuro-development, neural stem cells, mood disorders, brain injury and spinal cord injury. My customers have found EnCor’s reagents to be rock solid and versatile.

    In addition, Gerry and his team have proved adept at culturing our E18 hippocampal neurons and ESC derived hN2TM primary neurons. This is a big plus as we can actually see how the cells and markers could resonate together for use in cell based assays.

    Hippo_MAPT_DC1 Image: E18 hippocampal neurons stained with Tau (red) and Doublecortin (green). The two proteins overlap in the proximal dendrites (yellow) Axons (low doublecortin content) are red. Blue staining is the nuclear DNA.

    Futures

    I am excited by the glimpse of the future that Gerry shared. We can expect many new, novel and important markers in the coming months and years. In addition, he will be manufacturing various Enzyme-linked immunosorbent assays (ELISA). These kits have the potential to help clinicians diagnose the early onset of diseases like ALS, Parkinson’s and Alzheimer’s.

    For example, his company currently sells an ELISA kit for sensitive detection of Phosphorylated Neurofilament-H (pNF-H). Expression of this protein is up regulated in a variety of damage and disease states, and can be used to accurately quantify this up regulation. The kit can also detect pNF-H in the sera and spinal cord fluid (CSF) of animals with spinal cord and brain lesions. This protein is not normally found in sera or CSF, so its presence indicates recent axonal injury as a result of either damage or disease. This suggests pNF-H is a useful biomarker of neuronal and more specifically axonal injury or degeneration, a suggestion supported by a growing list of basic science publications on various animal models and patient types from Gerry’s research lab (e.g. Shaw et al. 2005, Lewis et al. 2008, Boylan et al. 2009, Lewis et al. 2010).

    Given the capabilities of EnCor’s markers, the development of more kits is coming. There could be a day in the not distant future where they give clinicians tools to better diagnose and monitor serious neurodegenerative diseases, leading to better disease treatment and management.

    I will keep you informed on Gerry’s and EnCor’s future developments.

    Dr. Ivan Rich and HemoGenix

    Stem Cells Testing Tools that enlighten Drug Discovery and Cell Therapy Researchers
    I am pleased to profile Dr. Ivan Rich. He is the founder, chairman and CEO of HemoGenix and an internationally recognized leader in hematology.  I am timing this profile to coincide with Neuromics launch of HemoGenix’s first to market fully standardized, proven and cost effective  ATP-based, in vitro bioluminescence and high-throughput screening (HTS) cell based assay systems.

    These assays represent best in class solutions for detecting and measuring cell viability, functionality, growth, proliferation and cytotoxicity of stem and progenitor cells for stem cell and basic research, cellular therapy, in vitro toxicity testing and veterinary applications.

    Hemogenix_Pic

     ivan-rich

    2000-Present- Hemogenix-CEO
    and Chairman

    1996-2000-Palmetto Richland Memorial Hospital

     1995-Second Thesis in Experimental Hematology, University of Ulm

    1981-1983-Post Doc University of Chicago

    1973-1978-Ph.D. University of Ulm, Biology

     

    Ivan’s journey leading to founding of HemoGenix provided him a unique blend of scientific, entrepreneurial and operational expertise.  These traits are the drivers that enable him to invent, successfully commercialize and continuously improve cell based assay systems. These systems meet a wide range of demanding requirements. These include, for example, meeting the requirement by Standards Organizations and Regulatory Agencies for “appropriate” and “validated” assays that can be used by cord blood banks and stem cell transplantation centers to determine whether a stem cell product has the necessary potency characteristics and can be released for transplantation into a patient…high standards indeed!

    The Back Story-Hematology and Hemopoietic Stem Cells

    Ivan received his PhD from the University of Ulm, in Germany in 1973 in Human Biology. He then completed a second thesis in 1995 in experimental hematology.  Our story starts here.  As a background we need to understand:  the hemopoietic stem cell compartment consists of cells which are responsible for maintaining the steady-state production of some two million red blood cells and two hundred thousand white blood cells every second of a person’s life!

    Beginning in 1973, he worked extensively with “classic” colony-forming cell (CFC) assay.  At the same time, He also gained experience in culturing erythropoietic progenitor cells (BFU-E and CFU-E) under low oxygen tension. His group was the first to demonstrate that macrophages grown in vitro could respond to low oxygen tension by regulating erythropoietin production at a local level. His group also demonstrated the role of HOXB6 in erythropoietic development as well as the role of the Na/H exchanger in hematopoiesis. “Necessity being the mother of invention”, Ivan began developing these assays into miniaturized format.  Assays necessary for fully understanding the potential and associated risks of using of these cells for human therapies.

    This opened the door for him to do a post doc with the late Dr. Eugene Goldwasser at the University of Chicago. Dr. Goldwasser was renowned for discovering the first partial amino acid sequence of erythropoietin (EPO). This discovery eventually led to the production of human recombinant EPO by Amgen and the development of first EPO related therapeutic (Epogen). It is used to treat anemia from kidney disease and certain cancers.

    We now move to Palmetto Richland Memorial Hospital in South Carolina where Ivan served as Director of Basic Research for Transplantation Medicine. From this research,  we learn that the most primitive stem cells have the greatest potential for proliferation and long-term reconstitution of the hemopoietic system, while the most mature stem cells have only short-term reconstitution potential. These primitive cells then become the most excellent candidates for future therapies. BUT how do we know the population of cells derived from cord blood or bone marrow contain the required population of potent and safe (phenotypically stable) primitive stem cells for effective therapies? We can ask the same questions for other stem cell populations that are candidates for therapies. These include mesenchymal stem cells, neural stem cells and others.

    Introducing Quantitative, Accurate and Proven High Throughput (HTS) Stem Cell Assays

    Ivan and HemoGenix began answering these questions in 2002 with help from National Cancer Insitute (NCI) SBIR grants. This led to the successful launch of the HALO® family of kits. These kits are based on Bioluminomics™ which is the science of using the cell’s energy source in the form of ATP (adenosine triphosphate) to provide us with a wealth of information. The production of ATP is an indicator of the cell’s cellular and mitochondrial integrity, which, in turn, is an indicator of its viability and cellular functionality. ATP also changes in proportion to cell number, proliferation status and potential, its cytotoxicity and even its apoptotic status.

    HemoGenix continues to develop and evolve kits key to developing effective and safe stem cell related drugs and cell based therapies.

    Practical Applications

    Here are examples of the kits in action.

    • HemoGenix and Vitro Diagnostic-Via this partnership, LUMENESC kits for mesenchymal stem cells include high performance growth media for research, quality control or potency or cytotoxicity to the mesenchymal stem cell system
    • LumiSTEM™ for testing  hNP1™ Human Neural Progenitors Expansion Kit-enables  fast, accurate and multiplex detection system for hastening advances in drug safety and discovery as well as environmental toxicology. . LumiSTEM™[now LumiCYTE-HT]  kits are used for in vitro detection of liver toxicity, with an overall reduction in drug development cost for drug candidates
    • High Throughput (HTS) Screening of Multiple Compounds using HALO®-(to learn more see: TOXICOLOGICAL SCIENCES 87(2), 427–441 (2005) doi:10.1093/toxsci/kfi25). Eleven reference compounds from the Registry of Cytotoxicity (RC) and eight other compounds, including anticancer drugs, were studied over an 8- to 9-log dose range for their effects on seven cell populations from both human and mouse bone marrow simultaneously. The cell populations studied included a primitive (HPP-SP) and mature (CFC-GEMM) stem cell, three hematopoietic (BFU-E, GM-CFC, Mk-CFC) and two lymphopoietic (T-CFC, B-CFC) populations. The results reveal a five-point prediction paradigm for lympho-hematotoxicity.
    HSC Toxicity Data

    HSC Toxicity Data

    Futures

    The dawn is breaking for stem cells therapies. These cells are the reparative engines for damaged cells in our bodies. These therapies have the potential to alleviate the world’s most insidious, chronic and costly diseases. Tools that enable us to understand the true properties and potency of these cells lower the cost of discovering drugs and cell based therapies.

    I look for more tools to spring from the vision of Dr. Ivan Rich that will play an ever increasing and important role in the world of basic stem cell research, stem cell based therapies and regenerative medicine. I plan to keep you updated on the evolution and capabilities of these inventions.

    Dr. Steve Hall knows Stem Cells

     
    Developing New Methods, Applications and Reagents for Regenerative Medicine and Stem Cell Research.
     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 be 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

    Dr. Steve Hall

    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

    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.

    Coming Soon-Dr. Steve Hall

    Dr. Steve Hall

    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!

    Featuring Dr. Pat Carr

    Amyotrophic Lateral Sclerosis (ALS)-New Twists on Root Causes

    Teacher, Mentor and Friend    Dr. Pat Carr has been a key figure in helping shape the direction of my company. He has a gift for communicating the nuances of his research and coaching me on how to best serve labs like his. Based on these interactions, it came as no surprise to learn of his being Recognized for Excellence in Teaching, Research and Service at University of North Dakota.

    “Dr. Carr has a magic way of teaching,” said second-year medical student, Tyson Bolinske. “He is able to take the most difficult topics and, through detailed notes, logically break down the material.

    From a recent dialog, I learned of his growing work on the Ventral Horn and search for root causes of Amyotrophic Lateral Sclerosis (ALS).   I wanted to learn more! I would like to thank Pat for agreeing to share his story and giving me the opportunity to feature highlights in  “News Behind the Neuroscience News”.

     Information on ALS

    ALS is an insidious disease.  It is a progressive neurodenerative disease that is always fatal. Approximately 5600 new cases are diagnosed each year. Average survival is typically 3-5 years from onset. The most common form of ALS in the United States is “sporadic” ALS. It can happen to anyone at anytime.  The other is the inherited form named “Familial” ALS (FALS). Only about 5 to 10% of all ALS patients appear to have FALS. As the disease progresses the symptons become more acute. Paralysis spreads through the body affecting  speech, swallowing, chewing and breathing. Ventilator support is need in late stages

     Pat’s Journey

    Pat took the “road less traveled”.  He was a passionate hockey player in Canada. He  concluded in his late teens that he was not at a level to take this road to wealth and fame.

    Pat Carr

    Pat Carr

    06/04–present Associate Professor, Department of Anatomy & Cell Biology, School of Medicine and Health Sciences, University of North Dakota 

    1996–98 Research Associate/Adjunct Assistant Professor/Auxilliary Assistant Professor, Department of Anatomy;Wright State University

     07/98–06/04 Assistant Professor, Department of Anatomy & Cell Biology, School of Medicine and Health Sciences, University of North Dakota

    Postdoc, National Institutes of Health, Neuroscience, 1994-96

    Postdoc, University of Manitoba, Neuroscience, 1992-1994    

    Ph.D., University of Manitoba, Physiology, 1992

    Next was a stint as an automechanic in Brandon, Canada. The discipline and logic involved in fixing cars catalyzed an interest in Science which led to him going to Brandon University to study Geology. When the oil market collapsed in 1983, he decided to change his studies to Zoology and earned a BS in 1984.

    A passion was sparked when he did field research in the Canadien Rockies studying parasites in Columbian Ground  Squirrels. He loved it, but recognized the limited value of continuing thsese studies. This lead to the wide open field of Neuroscience and the opportunity to study and solve problems that could benefit mankind. His graduate work at University of Manitoba and focusing on Neuropathic Pain and the Dorsal Horn. He then moved on to studying Ventral Horn and Motor Control Function for his Post Doc at Wright State.

    From Pain to ALS

    It was Pat’s work in Pain at the University of North Dakota that brought me into initial contact with him. He generously put some of our key Pain/Inflammation and  Neurotransmission Research Antibodies through their paces. These included some of our Neuropeptide and Neuropeptide Receptors , P2X Receptors and TRPV1s (Vanilloids).

    His previous work in studying the Ventral Horn combined with a colleagues mouse model of ALS combined to create a prefect opportunity to advance the understanding of ALS.  Pat cautioned me with this insight:  ”sometimes it is  not what you want to study; it is what you can study.  The model is  SOD1 (superoxide dismutase 1) which is core to FALS.(occurs in only about 10% of the ALS cases).

    Pat is broadening the play field by looking at what else is happening in sporadic ALS vs FALS. Specifically, he is looking at modulation of alpha Motor Neurons and how the activity of adjacent Renshaw Cells impact signaling and modulation.  Renshaw Cells act as a “governor” on the activity of these alpha Motor Neurons. 

    He is drilling down by studying the signaling of ChAT (Choline Acetyltransferase), VAChT (Vesicular acetylcholine transporter) and related molecules. By gaining a deeper understanding of how Renshaw Cells signaling changes the activity of alpha Motor Neurons in ALS,  Pat and his team are taking steps towards discovering roots causes.

    As these root causes are further illuminated, I will be reporting specifics in my blog.