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  Newsletter Issue 7, 21 October 2015

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STEM CELL SOCIETY SYMPOSIUM 2015

"Opportunities & Challenges in Stem Cell Based Medicine"

17 -18 November 2015

Matrix Building
30 Biopolis Street, Singapore 138671

 

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Count-down to the Symposium!!!

 

 

 

Dear Members, Delegates, Friends, and Supporters,

 

the Newsletter Issue 7 introduces three of the symposiums' plenary speakers:
Outi HOVATTA, Karolinska Institute, Sweden
Karl TRYGGVASON, Duke-NUS, Singapore
Victor NURCOMBE, Institute of Medical Biology, Singapore

Enjoy reading about these three speakers and what they will talk about during the symposium.

Other Symposium Announcements

Upcoming Deadline:

1) Online registration closes: 30 October 2015

Make sure to book your seat before online registration closes in 9 days.

 

A tentative programme can be accessed HERE.

To learn more about the symposium, follow this LINK.

To register, click HERE.

Contact us HERE.

 

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Featured Speakers  

Outi HOVATTA

Karolinska Institute, Sweden

 
Abstract  
Chemically Defined Xeno-free Human Embryonic Stem Cells for Clinical Treatments

 

Human embryonic stem cells (hESC) are the most promising source of cells for regenerative medicine. We have now developed a method to establish and effectively upscale genetically stable ESC lines in completely chemically defined xeno-free conditions using human recombinant laminin 521 as the culture matrix.

We can also differentiate these cells in xeno-free defined conditions using LN matrices, retinal pigment epithelium as an example. We have established hESC lines also from single biopsied cells from eight cell embryos without destroying the embryo.

Biography Webpage PubMed

 

Professor in Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden, since September 1998.
Graduated as an MD in 1970 and PhD 1972 at the University of Helsinki. Worked previously as a research associate 1967-73 in the same university, and then as a resident and specialist Obstetrician Gynaecologist at Helsinki University Hospital 1973 -1986. Then worked as the Chief Physician and founder, Infertility Clinic, the Family Federation of Finland, and during 1995 -1998, and then as a visitng research fellow in the Imperial College School of Medicine at Hammersmith Hospital, London, UK 1995-1998, and as a Visiting Professor, University of Geneva, Switzerland in 2008.

Main research topics Human reproductive science and medicine, including development of cryopreservation methods for human ovarian and testicular tissues, reproductive function in Turner syndrome, development of human oocytes and ovarian follicles in vitro. During the latest 15 years, human embryonic stem cells, their banking and differentiation to several cell types for use in regenerative medicine, including Retinal Pigment Epithelium (RPE).

Interview  

What was the first phenomenon you can recall that fascinated you about science?

Already as a child, I became fascinated by wildlife when trekking in the woods with my father. As a teenager I wanted to know everything about cells. Then it when on at school and university, and I chose to become a scientist. Medical faculty looked natural to me.

What is your most memorable career achievement?

My most memorable career achievment was being elected to my present professorship in open competion at the Karolinska Institute in Stockholm.

Who are your scientific heroes/role models and why?

My role models were professor Anne McLaren in Cambridge, and professor Anne-Grete Byskov. They both showed that by focused research one can achieve innovations in reproductive and stem cell sciences.

Which scientist/clinician has made the biggest impact in your field and why?

Professor Robert Edwards, the Nobel laureate, showed that if you know that you are right, you have to go on and demonstrate that by high quality science, even if other people do not believe you and try to pull you down.

What publication(s) had the most influence on you and why?

Prof  RG Edward’s successful in vitro fertilisation (IVF) article in 1978, and his and Simon Fishel's article showing how stem cells grow out from a human blastocysts in Science in 1986.

What influenced you to pursue stem cell research?

As a medical student in the University of Helsinki, in 1969, I had the possibility syart to start a cell culture project. The enthusiasm in cell cultures became strong when  IVF became possible. I knew that IVF was my field. Working with human embryos for several years, it was natural for me to start making human embryonic stem cells in Karolinska Institute in 2000.

How are challenges relating to upscaling of stem cell culturing for large scale manufacturing being overcome?

They have already been overcome by establishing a method to up-scale them in their natural environment (Rodin et al Nat Comm 2014).

Where do you think stem cell research will be with regards to clinical application in 5-10 years’ time?

Within 5-10 years, stem cells are being used in treatment of severe diseases.

 

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Karl TRYGGVASON

Duke-NUS, Singapore

 

 
Abstract  
Laminin-based Matrices in Defined Human Stem Cell Differentiation Protocols  

Basement membrane (BM) laminins are important for cell differentiation and phenotype stability. We have produced most laminin (LN) isoforms and demonstrated important properties and applications. We have used LN-511 and LN-521 to clonally derive new hES cell lines in defined and xeno-free conditions. LNs are also useful as cell culture substrata in chemically defined and xeno-free differentiation protocols, such as for generating cardiomyocytes and endothelial cells (EC). The heart ventricle contains LN-221 and LN-521 as major laminin isoforms, in addition to lesser amount of LN-211, as well as LN-411 and LN-421, which are located in blood vessel BMs. We have used BioLamina´s recombinant human LN-221 and LN-521 to mimic the natural in vivo matrix environment to differentiate hES cells to cardiomyocytes. This defined matrix provides robust support for differentiation of hES cells into cardiomyocytes. We have characterized the cells at different differentiation stages using RNAseq, immunostaining, patch clamp, MEA and cytotoxicity assays.

The progenitors continue to differentiate for up to 120 days into spontaneously beating cardiomyocytes expressing >80 % TNNT2. Different progenitors are being tested for myocardial infarct repair in SCID mice. In order to generate cardiomyocytes harboring mutations found in human heart disease, we have inserted specific titin mutations into pluripotent hES cells that have been clonally expanded before their differentiation to cardiomyocytes. Such cells can provide a model system for genetic cardiac disease. We have also differentiated hES cells using biorelevant laminins as a culture substrate to achieve more than 95% ECs co-expressing VEGFR2, CD31 and VE-cadherin. These cells form tube-like structures and take up acetylated LDL. The data demonstrate usefulness of cell-specific laminins in cell differentiation and phenotype stability. Cells differentiated using laminin-based xeno-free and chemically defined protocols may provide high clinical quality cells for cell therapy in regenerative medicine..

Biography Lab webpage PubMed  

Karl Tryggvason, MD, PhD, Senior Professor of Medical Chemistry, Karolinska Institute, Stockholm, and Professor in Diabetes Research at Duke-NUS, Singapore. A long track record in basement membrane research. Current work concerns laminins and their use in hES cell differentiation, phenotype stability,  and cell differentiation, and on the causes of kidney filter diseases. He has published over 400 research articles.

He is a member of the Swedish Royal Academy of Sciences, and has been member of the Nobel Assembly and Committee at the Karolinska Institute for almost two decades. He has received several international awards, and cofounded three biotech companies.

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Victor NURCOMBE

Institute of Medical Biology, Singapore

 

 

Abstract  

Best in Class: Enhanced Self-renewal and Therapeutic Potential of Adult Human Mesenchymal Stem Cells Cultivated in Selected Heparan Sulfates

 
We are currently engaged in helping to position Singapore as a leader in adult stem cell-based therapies by engineering a cost-effective and safe platform to supply high quality human bone marrow-derived mesenchymal stem cells (MSCs) to clinicians in quantities previously unavailable for immediate transplantation for the treatment of trauma and disease. Current best practice to cultivate therapeutic numbers of MSCs (~500 million cells per patient) relies on isolating cells from a patient’s bone marrow and culturing them in expensive protein growth factors that readily degrade and require excessive dosing, and/or the use of immuno-selection methods that can adversely affect the potency of the cells. Also, because bone marrow aspirates contain < 0.01% MSCs, and these cells remain quiescent when isolated, achieving therapeutic numbers is problematic and has greatly hindered their therapeutic appeal. We propose a game-changing solution, namely culture supplementation with carbohydrate-based macromolecules, more precisely a particular heparan sulfate sugar tuned to bind and activate the endogenously produced mitogen FGF-2. This acts to increase MSC proliferation while preserving the stem-like quality of the cells, all in the absence of costly exogenous growth factors. We are cultivating these cells under strict adherence to the guidelines developed by the ISSCR and ISCT at GMP-grade and subjecting them to GLP safety/toxicity testing prior to banking. We have demonstrated that MSC’s cultivated this way are “best-in-class” by profiling their cell surface antigens and multipotentiality. Their in vivo efficacy is also being exemplified in rat and porcine models of cartilage trauma. We are seeking to gain approval from the HSA to begin clinical studies in Singapore and to offer this platform to clinicians shortly thereafter.
BiographyLab webpage PubMed  
Victor Nurcombe has engaged in biomedical research for over 30 years with an emphasis on developmental biology and carbohydrate biochemistry, In 2003, he joined A*STAR Institute of Molecular and Cell Biology in Singapore as a Principal Investigator in stem cell biology and 2008, he became a Senior Principal Investigator within A*STAR’s newly formed Institute for Medical Biology where he presently co‑directs a laboratory with Dr. Simon Cool. His current work has centered on how the carbohydrate component of the extracellular matrix controls stem cell decisions by regulating growth factor access to their surfaces. Dr. Nurcombe currently holds the position of Honorary Professor at the LKC School of Medicine, NTU-Imperial College London, and previously at the University of Lille, France. Prior to joining A*STAR, he was a Reader and Associate Professor at the University of Queensland, Australia, where he also led the developmental biology program. In addition, Dr. Nurcombe has worked at the Walter & Eliza Hall Institute at the Royal Melbourne Hospital, and as senior lecturer at the University of Melbourne. Dr. Nurcombe received his PhD in developmental neurophysiology from the University of Sydney. He was awarded both the CJ Martin Fellowship and Humboldt Fellowship to initiate his postdoctoral training at the Max-Planck Institute for Biochemistry in Munich. He received his MBA from the Nanyang Business School at Nanyang Technological University and a Diploma in commercial and contract law from Singapore Polytechnic. Dr. Nurcombe has co-authored over 150 peer-reviewed journal articles and 11 book chapters, has co-filed over 80 patents in 11 patent families and has raised over $90 million in grant monies as a named investigator
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