Third International
StemMass-2008:
‘Stem Cells & Regenerative Medicine-2008 Meeting’
“Molecular Embryology to Tissue Engineering & Therapeutics”
Venue: Hilton Garden Inn
420 Totten Pond Road, Waltham, MA, 02451 USA
April 7 – 8, 2008

'A Unique Theme to Combine Stem Cell Discovery with Organ Regeneration'

Target Audience: 150
Total Speaker Presentations: 30
Total Poster Presentations: 20
Total Exhibit Booths: 20

AGENDA/SPEAKERS

Click Here For Detailed Agenda

Monday, April 7, 2008
7:00 – 8:30 A.M: Registration Open
7:30 – 8:45 A.M: Continental breakfast
9.00 AM – 6.00 PM Scientific Sessions
Tuesday April 8, 2008
7:00 – 8:30 A.M: Registration Open
7:30 – 8:45 AM: Continental breakfast
8.00 AM – 4.00 PM Scientific Sessions


Scientific Advisory Committee:

	Krishnarao Appasani, PhD., MBA (Chair) Founder & CEO GeneExpression Systems, Inc. Waltham, MA USA
	Nagy Habib, PhD. Professor, Imperial College of London Hammersmith Campus, London, United Kingdom
	Ulrich Hoffmueller, PhD., MBA Chief Business Officer Epiontis GmbH 12489 Berlin, Germany

Keynote Speakers:

	Keynote Speaker on April 7 Ole Isacson , Dr. Med. Sci., Professor of Neurology & Director, Neuroregeneration Laboratory McLean Hospital & Harvard Medical School Belmont, MA, USA Title: TBA
	Keynote Speaker on April 8 Harvey F. Lodish, PhD. Member, Whitehead Institute Professor of Biology & Bioengineering Massachusetts Institute of Technology Cambridge, MA, USA Title: microRNAs that regulate hematopoiesis and adipocyte differentiation

Other Speakers:

	Laurie Jackson-Grusby, Ph.D. Assistant Professor of Pathology Children's Hospital &, Harvard Medical School Boston, MA, MA, USA Title: TBA
	Sean M. Wu, M.D. Ph.D. Principal Investigator, Cardiovascular Research Center Massachusetts General Hospital & Harvard Stem Cell Institute Boston, MA, USA Title: TBA
	Lilian Wikström, PhD. Head of Research NeuroNova AB Stockholm, Sweden Title: TBA
	David T. Harris, PhD. Professor of Immunobiology Director, Cord Blood Registry, Inc. University of Arizona Tucson, AZ, USA Title: The Pluripotential Nature of Cord Blood Stem Cells: Data Obtained From In Vitro, Animal and Patient Studies
	Jennie P. Mather, PhD. Founder, President and Chief Scientific Officer Raven Biotechnologies, Inc. South San Francisco, CA, USA Title: Tumor Stem Cells: Uses in Drug Discovery
	Budd A. Tucker, PhD. Postdoctoral Fellow in the Lab of Dr. Michael Young Schepens Eye Research Institute Boston, MA, USA Title: Transplantation of Progenitor Cell/MMP2- Polymer Constructs: Breaking old barriers
	Howard J. Leonhardt Founder & Chief Technology Officer BIOHEART, INC. Sunrise, FL, USA Title: Summary Review of Myoblast Transplantation for Heart Failure Research of 20 Years 1988 to 2008
	Tasneem Zahir, PhD. Postdoctoral Research Fellow Dept. of Chemical Engineering & Applied Chemistry University of Toronto Toronto, ON, Canada Title: TBA
	A. Fawad Faruqi PhD. Biochemical Technologies Corning Incorporated Corning, NY, USA Title: Development of 3D surfaces for cell culture
	Dong-Wook Kim, PhD. Professor & Director of Korean Stem Celle Research Center Yonsei University Medical Center Seoul, Korea Title: Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells
	Joydeep Goswami, PhD., MBA. Vice President, Stem Cells & Regenerative Medicine Invitrogen Corporation Carlsbad, CA, USA Title: Stem Cell Engineering - Making Stem Cells Talk
	Ralph Brandenberger, Ph.D. Director, Process Sciences Geron Corporation Menlo Park, CA, USA Title: TBA
	Paul Kemp, PhD. Chief Scientific Officer Intercytex Manchester, UK Title: Examining successful paths and considerations when getting a product to market
	Alexander Meissner, Ph.D. Assistant Professor Dept. Stem Cell and Regenerative Biology Harvard University, Harvard Stem Cell Institute & Associate Member Broad Institute of MIT and Harvard Cambridge, MA, USA Title: TBA
	Vincent Ronfard, PhD. Chief Scientific Officer & VP Research Organogenesis, Inc. Canton, MA, USA Title: Allogenic Stem Cell Therapy to Repair Damaged Skin: Current Status and Future Vision
	Stefan Przyborski, PhD. Director & Chief Scientific Officer ReInnervate Limited & Reader in Stem Cell Biology University of Durham, Durham, UK Title: Development of technology to enhance the growth of cultured stem cells and their derivatives
	Massimiliano Cerletti, PhD. Fellow, Div. of Developmental and Stem Cell Biol Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Title: Therapeutic Function of Skeletal Muscle Stem Cells
	Dr. Tracy Gentry Director of Preclinical Development Aldagen, Inc., Durham, USA
	Dinender K. Singla, PhD, FAHA Associate Professor of Medicine & College of Medicine, University of Central Florida, Orlando, FL, Title: Cardiac Repair and Regeneration in the Infarcted Heart"?
	Tan A. Ince, PhD, MD. Associate Pathologist & Instructor of Pathology Brigham and Women's Hospital & Harvard Medical School Boston, MA, USA Title: TBA

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Key Sessions

Cell Differentiation and Reprogramming
Self-renewal and Maintenance
Human & Cancer Stem Cells & Propagation
Transcriptional Controls of Stem Cells
Applications of Stem Cells in Human Diseases
Tissue Organ Culture and Transplantation
Biopolymer Applications in Tissue Engineering
Stem Cells Towards Developing Drugs & Therapeutics


Exhibitors are welcome to reserve their booth space early!

Please contact if you are interested in speaking in the scientific or Technology workshops of this meeting.

GeneExpression Systems, Inc.
P.O. Box 540170
Waltham, MA 02454 USA
Tel: (781) 891-8181
Fax: (781) 891-8234
E-mail: Genexpsys@expressgenes.com
www.expressgenes.com

Poster Abstract Submission by March 6, 2008

ALL ABSTRACTS

The Pluripotential Nature of Cord Blood Stem Cells: Data Obtained From In Vitro, Animal and Patient Studies
David T. Harris, PhD. Professor of Immunobiology, University of Arizona and Cord Blood Registry, Tucson, AZ

David T. Harris, Michael Badowski and Heather Brown
Dept. Immunobiology, University of Arizona and Cord Blood Registry.
Tucson, AZ

Cord blood stem cells (CBSC) have been used for transplant to treat thousands of patients with malignant and genetic hematological disorders. More recently CBSC have been investigated in several regenerative medicine applications. We sought to determine the pluriopotential nature of this stem cell source. In vitro we were able to derive endothelial, epithelial and neural tissues. CBSC were also beneficial in animal models of myocardial infarction, type I diabetes, ophthalmic tissue engineering, orthopedic reconstruction, and wound healing. CBSC have now been utilized in patients with type I diabetes, anoxic brain injury, traumatic brain injury and cerebral palsy, with apparent beneficial results. Two such patients (one with anoxic brain injury and one with cerebral palsy) will be presented in more detail.

Transplantation of Progenitor Cell/MMP2- Polymer Constructs: Breaking old barriers

Budd A. Tucker, PhD., Postdoctoral Fellow in the Lab of Dr. Michael Young, Schepens Eye Research Institute & Harvard Medical School, Boston, MA USA

The ability of the adult mammalian central nervous system (CNS), including the retina, to regenerate is extremely limited and generally restricted to aberrant local sprouting. This can be attributed to several factors, including enhanced expression of inhibitory extracellular matrix (ECM) and cell adhesion molecules, many of which are found in areas of glial hypertrophy and scar formation. To overcome these barriers, we have successfully delivered active MMP2/progentior cell-polymer constructs directly to the site injury, enhancing donor cell integration, differentiation and potentially regeneration in a mouse retinal degenerative model.

Financial Support: Foundation Fighting Blindness, Department of Defense, NSERC, Discovery Eye and Lincy Foundations.

Therapeutic effects of transplanted stem cell derived neurons in neurodegenerative diseases
Ole Isacson, M.D. (Dr Med Sci), Professor of Neurology (Neuroscience), Harvard Medical School; Director of Center for Neuroregeneration Research at McLean Hospital/Harvard Medical School; and NINDS Morris K. Udall Parkinson's Disease Research Center of Excellence, Belmont, MA USA.

A biotechnological and large-scale medical application of transplantation of fetal DA cells into brains of Parkinson’s patients could be achieved by obtaining similar cells derived from human embryonic stem (hES) cells (L.M. Bjorklund et al, 2002). hES cell differentiation protocols have been accomplished for generating DA neurons. Criteria now exist to achieve functional neuronal replacement from ES cells, in the absence of tumor formation (Pruszak et al., 2007). The biological insights and methods to generate therapeutically relevant cells largely depend on understanding normal brain development and discovering the in vitro conditions for appropriate hES cell differentiation, while the medical opportunities for successful intervention by cell therapies in neurological diseases are best defined by the capacity for physiological integration of the new cells with the host brain (Isacson et al 2003, 2008).

Summary Review of Myoblast Transplantation for Heart Failure Research of 20 Years 1988 to 2008
Howard J. Leonhardt, Founder, Executive Chairman & Chief Technology Officer, Bioheart, Inc. Sunrise, Florida 33325 USA
Michael Brown, M.D., Ph.D., Howard Leonhardt, Jason Griffeth, Richard Spencer, Kristin Comella – Bioheart, Inc., Sunrise, Florida

Bioheart, Inc. is a company focused on the discovery, development and commercialization of cell therapies derived from a patient’s own body for the treatment of heart damage.  The company is currently conducting Phase II/III clinical trials at 23 centers (330 patients) using autologous muscle stem cells as a treatment of heart failure patients. Bioheart also has other product candidates in development including a gene-modified myogenic cell therapy for the treatment of heart failure and an adipose tissue derived stem cell therapy for the acute treatment of heart attacks and ischemia. With a combination of capital raised and grants the company has invested nearly $100 million in cell therapy reseserch for heart failure since it's founding in 1999.  The company holds rights to over 35 related patents and patents pending.

Stem Cell Engineering - Making Stem Cells Talk
Joydeep Goswami, PhD., MBA., Vice President, Stem Cells & Regenerative Medicine, Invitrogen Corporation, Carlsbad, CA, USA

Stem Cells have a fascinating potential in unlocking the secrets to human development and regeneration. They also promise better human cellular models for more accurate drug screening studies for toxicity and efficacy. To fully harness this potential, however, will require us to be able to understand precisely when different pathways in the cells are activated in response to stimuli, and as they make their choices of self-renewal vs. differentiation. We describe one way to fully harness the potential of stem cells.

Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells
Dong-Wook Kim, PhD., Professor & Director of Korean Stem Celle Research Center
Department of Physiology, Yonsei University Medical Center, Seoul, Korea
 
We developed a novel method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (1) they can be passaged for a long time without losing their differentiation capability into DA neurons; (2) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86 % TH+ neurons/total neurons); (3) the induction of DA neurons from SNMs only takes 14 days; and (4) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also would reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a Parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large scale generation of purer and functional DA neurons for future clinical applications.

Therapeutic function of skeletal muscle stem cells
Massimiliano Cerletti, PhD., Joslin Diabetes Center, Division of Developmental and Stem Cell Biology, Harvard Medical School, Boston, MA 02215, USA

We have used cell surface marker expression and fluorescence activated cell sorting to purify from the satellite cell pool a distinct population of skeletal muscle precursor (SMP) cells that act as adult muscle stem cells. When intramuscularly transplanted into dystrophin-deficient mdx mice, isolated SMPs, but not other, more differentiated muscle populations, contributed to the formation of hundreds of new muscle fibers, restored dystrophin expression, and significantly improving muscle contractile function. This system, we will not only allow investigation of fundamental properties of stem cells, such as their ability to self-renew and to support tissue regeneration, but will provide an exciting, new therapeuthic possibility for the treatment of muscle degenerative disorders, such as Muscular Dystrophy.

Development of technology to enhance the growth of cultured stem cells and their derivatives
Stefan Przyborski, PhD. Director and Chief Scientific Officer, ReInnervate Limited, UK
Reinnervate specializes in the development of enabling technology to help overcome the limitations of current cell culture techniques and methods to control cell differentiation in vitro. Its proprietary technologies will facilitate research into the growth and function of cultured cells and has direct relevance to stem cell biology. The Company has three primary areas of interest namely; the development of more favourable growth conditions for cells in vitro through the design and manufacture of specialized

Allogenic Stem Cell Therapy to Repair Damaged Skin: Current Status and Future Vision
Vincent Ronfard, PhD., Vice President Research, Organogenesis Inc. Canton, MA, USA

Over the last 30 years, applied research has focused on the development of new therapeutic agents based on cellular and tissue therapy and the novel concept of bioengineered tissue has emerged. These products were initially designed for the treatment of venous leg ulcers and diabetic foot ulcers, there are reports of their application in other indications, such as epidermolysis bullosa, burns and acute wounds. The mechanism of action of these bioengineered products is not fully elucidated, and different products may have different modes of action. This talk will provide an overview of the literature regarding the use of allogenic cells in the fabrication of a bioengineered construct including the importance of cell sourcing, manufacturing aspects and the mechanism of action of these products, and lastly discusses the future development of allogenic stem cell use.

Examining successful paths and considerations when getting a product to market
Paul Kemp, PhD., Chief Scientific Officer, Intercytex Ltd., Manchester, UK

My presentation focus on the following issues: Determining product specifications and market size; Deciding which registration classification to use; Integrating manufacturing, regulatory and clinical groups to maximise product development; Identifying cost of goods and economies of scale; Establishing process development when and how cell culture equipment that enables routine three dimensional cell growth; the design and synthesis of small molecules that control cell differentiation in a robust and consistent manner; and the development of new strategies in neural stem cell research.

Established solid tumor stem cell lines provide pure stable populations for studies of cell surface protein expression
Jennie P Mather*, Penny E Roberts*, Peter Young*, Jeff Hooley*, Tony Liang*.
Raven biotechnologies, inc. South San Francisco, CA, USA 94080 and
#Kaiser Permanente, Los Angeles, CA

Cancer Stem Cells(CSC) are a minor, phenotypically distinguishable population of cancer cells which can self-renew, reproduce a tumor from a small number of cells, and differentiate to tumor daughter cells. Most studies of solid CSC to date have relied on prospective marker(s) to enrich for a population containing CSC. This approach relies entirely on mathematical differences between the enriched and remainder populations. Since neither population is pure, the mathematical proof remains weak. An established cell line derived from the CSC would obviate many of these problems by providing a pure, stable population of CSC for biological studies. We have established pure, stable populations of CSC from prostate, colon, breast, pancreatic, and skin tumors using defined media to select for the CSC population. By analyzing >100 cell surface in the selected populations, and clones derived from them and from tumors grown from these CSC in xenografts of SCID mice, we can arrive at the following conclusions:
CSC lines can self renew and some have exceeded 100 population doublings
CSC lines can from tumors from 100 cells when implanted in the renal capsule
Expression of cell surface markers is stable to passage <20% change over 30 passages
Expression of markers does not change with cloning, ie populations are homogeneous
We have used these lines to define the expression of 25 markers some of which have not yet been reported to exist on CSC and are present on the CSC of all of the above tumor types.

Cardiac regeneration: iPS, ES, or endogenous cells?
Sean M. Wu, M.D. Ph.D., Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Cell-based therapy holds tremendous promise for a variety of cardiovascular diseases. The biology of cardiac differentiation from pluri- or multipotent stem cells provides critical insights into the logic of cardiac lineage commitment. We have recently described the isolation and characterization of a multipotent cardiac progenitor cell population from both embryonic stem (ES) cells and the developing mouse embryo. The derivation of induced pluripotent stem (iPS) cells from mouse and human fibroblasts by the introduction of Oct4, Sox2, Klf4 +/- c-Myc suggests that autologous iPS cell-derived cardiac progenitor cells may be feasible for clinical studies in the near future. This talk will address the biological similarity and differences between iPS and ES cell-derived cardiac progenitor cells and their implications for the use of these cells in cardiac regenerative therapy.

Ultra-Web™ synthetic surface for 3D-like cell culture
A. Fawad Faruqi PhD. Science and Technology, Corning Life Sciences Corning Incorporated, Corning, NY, USA

The majority of cell culture work has been performed on 2D cell culture surfaces such as plastic and glass. It is now widely accepted that cells cultured on 3D surfaces behave differently when compared to cells cultured on 2D surfaces. This is particularly true of primary cells that have not adapted to flat surfaces. The Corning Ultra-Web™ synthetic surfaces consist of a network of nanofibers that provide a 3D-like topography for cell culture. We report here the improvement of cellular functions for different cell types when cultured on the Ultra-Web™ synthetic surface.

Cell origin influence on tumor phenotype
Tan A. Ince, PhD, MD., Instructor of Pathology & Associate Pathologist, Harvard Medical School & Brigham and Women's Hospital, Boston, MA, USA

We developed a chemically-defined culture medium that allows direct comparison of isogenic tumors that are derived from distinct breast epithelial cell subtypes.  This revealed that tumor initiating stem cell phenotype can be strongly influenced by the phenotype of the normal mammary epithelial cell type. While one transformed cell type formed tumor when ten cells were injected into mice, other cell transformed cell types required injection of 105 cells to form tumors. Hence, analyses of normal cell populations that give rise to various tumor types will be essential for a complete understanding of tumor phenotypes. 

Basis for using aldeyde dehydrogenase bright cell populations in the clinic
Tracy Gentry, MS., MT. Director of Preclinical Development, Aldagen, Inc., Durham, USA

Aldagen is a biotechnology company advancing a pipeline of clinical-stage regenerative therapies. Aldagen’s proprietary technology sorts highly active cell populations (ALDH bright cells) based on aldehyde dehydrogenase expression.  Hematopoeitic, mesenchymal, endothelial, and neural stem cells all express high levels of ALDH. The company is currently involved in four clinical trials using ALDHbr cells. ALD-101 and ALD-151 are being used to accelerate engraftment in pediatric patients receiving umbilical cord blood transplants to treat metabolic disorders and malignancies, respectively. ALD-201 and ALD-301 prepared from autologous bone marrow are being used to treat chronic heart failure and critical limb ischemia, respectively.  We will discuss the basis for the use of ALDH bright cells in these clinical indications and preclinical observations that led to our current clinical program, including characterization of both phenotypic and functional properties of ALDHbr cells.

Stimulation of endogenous neurogenesis - a new approach to treating Parkinson’s disease
Lilian Wikström, PhD., Head of Research, NeuroNova AB, Stockholm, Sweden

Finding new treatments for debilitating diseases like Parkinson’s disease, Alzheimer’s Disease, Huntington’s Disease and stroke is one of the most challenging tasks in medical research. Stem/progenitor cells in the adult brain are capable of dividing and giving rise to new neuronal and glial cells, suggesting that the brain has an intrinsic regenerative capacity. Since adult stem/progenitor cell activity can be pharmacologically stimulated, enhanced endogenous neurogenesis offers new perspectives for the treatment of several currently incurable neurodegenerative diseases. NeuroNova has identified compounds that are able to stimulate endogenous stem/progenitor cells, and reverse of symptoms in animal models of Parkinson’s Disease.

Cell Characterization in Regenerative Medicine Applying DNA Methylation Markers
Georg Wieczorek, PhD., Scientist R&D, Epiontis GmbH, Berlin, Germany

Georg Wieczorek1, Stephen Rapko2, Udo Baron1, Leslie Wolfe2, Sven Olek1, Ulrich Hoffmueller1
1) Epiontis GmbH, Berlin, Germany, 2) Genzyme Corp., Cambridge, MA

Reliable cell characterization plays a pivotal role in tissue engineering and regenerative medicine. Quality control based on protein or mRNA expression omits the key properties of cellular therapeutics, long term cell type identity and specialization.
DNA-methylation analysis possesses large potential for cell characterization. Specific methylation patterns correlate with differentiation states, cell type and long-term cell functions. Using genome-wide discovery methods and knowledge-based approaches, DNA-methylation candidate markers were identified that discriminate chondrocytes from potentially contaminating synovial fibroblasts in the autologous chondrocyte product Carticel®. The devised sample classification model was validated in a blinded study. Using methylation sensitive real time-PCR methods, a standard release assay for the therapeutic product has been developed.
These results demonstrate that DNA-methylation analysis qualifies as a suitable technique for cell characterization and routine release quality control tests for products in tissue engineering and regenerative medicine.

Developing Cell-Based Therapeutics from Human Embryonic Stem Cells
Ralph Brandenberger, Ph.D., Director, Process Sciences, Geron Corporation, Menlo Park, CA

Geron develops human Embryonic Stem Cell (hESC)-based cellular therapeutics in several disease areas, including neural cells for spinal cord injury, cardiomyocytes for heart disease, and pancreatic islet β cells for diabetes. hESCs can be propagated indefinitely in vitro and can be differentiated into all major lineages of somatic cells in the body. These two properties provide the foundation for the development of “off-the shelf” cell-based therapeutics. Data will be presented that Geron has reduced to practice the scaleable production of hESC that enable a business model for the manufacturing and distribution of hESC based therapeutics analogous to that of biologics.

Clinical Application of Adult Bone Marrow Derived Stem Cell Progenitors in Patients with Liver Disease
Dr. Natasa Levicar, Dept. of Surgery, Imperial College of London, Hammersmith Hospital, London W12 ONN, UK

Natasa Levicar1, Madhava Pai1, Myrtle Gordon2, Nagy Habib1
Department of Surgery1 and Haematology2, Imperial College London, Hammersmith Hospital Campus, London, UK

Recent advances in regenerative medicine, including haematopoietic stem cell transplantation have made the prospect of cell therapy and tissue regeneration a possible clinical reality. We have isolated, from mobilised and leukapheresed blood, a morphologically and phenotypically homogeneous subpopulation of CD34+ cells (~1%) that exhibits the necessary properties. We have demonstrated that these cells (OmniCytes) and/or their progeny generated within 2 weeks in culture express genes corresponding to stem cells (Rex-1, Oct-4, Nanog) hematopoietic (CD34, CD133, CXCR4), and hepatic cell differentiation (albumin, alfa-1 antitrypsin, vimentin, HGF, HNF3-B, transferrin). Furthermore, we have performed a phase I safety, toxicity and feasibility clinical study in five patients with liver insufficiency. Between 1 x 106 and 2 x 108 cells were isolated by leukapheresis and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicities and changes in clinical, haematological and biochemical parameters and followed up for 18 months. All patients tolerated the procedure well and there were no treatment-related side effects or toxicities observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. Our study showed considerable promise for the clinical application of liver stem cell therapy