Lung Disease

Lung Disease

Making Lung Cells from Pluripotent Stem Cells - Disease Modeling and Future Therapies

Human pluripotent stem cells (hPSCs) have the potential to provide inexhaustible sources of patient-specific cells, thus overcoming a major roadblock for many functional and pathological studies posed by the limited availability of patient-specific primary cells. Methods to differentiate hPSCs into specific cell types that exhibit functional characteristics of target adult cells hold great promise for patient-specific disease modeling, drug discovery and personalized medicine. In recent years, differentiation protocols for hPSC-derived airway epithelial cells have greatly improved the availability of cell models that enable studies of lung development and regeneration, as well as lung diseases, such as cystic fibrosis.

View this webinar presentation by Prof. Janet Rossant and Dr. Amy Wong, who discussed their research efforts to understand lung development and diseases using hPSC-derived lung epithelial cells in CF-patient specific models.



Dr. Janet Rossant
Dr. Janet Rossant
Senior Scientist and Chief of Research Emeritus
Hospital for Sick Children

University Professor
Department of Molecular Genetics, University of Toronto
Dr. Amy Wong
Dr. Amy Wong
Senior Research Associate
Hospital for Sick Children
Topics:

  • Efficient generation of definitive endoderm from hPSCs
  • Driving proximal lung differentiation from definitive endoderm
  • Developing high-throughput assays to assay CFTR function in cystic fibrosis versus control iPSC-derived lung epithelial cells
  • Culturing lung progenitors and cystic organoids (bronchospheres) from hPSCs
  • Disease modeling versus future cell replacement therapy - Where do we stand?
Dr. Janet Rossant
Senior Scientist and Chief of Research Emeritus
Hospital for Sick Children

University Professor
Department of Molecular Genetics, University of Toronto

Janet Rossant, CC, PhD, FRS, FRSC is Senior Scientist and Chief of Research Emeritus at the Hospital for Sick Children in Toronto and President and Scientific Director of the Gairdner Foundation. She is an internationally recognized developmental and stem cell biologist, exploring the origins of stem cells in the early embryo and their applications to understanding and treating human disease. She led the research institute at the Hospital for Sick Children from 2005 to 2015. She has received many honors and recognition for her work, including four honorary degrees, and election to the Royal Societies of London and Canada, and the National Academy of Sciences, USA.

Dr. Amy Wong
Senior Research Associate
Hospital for Sick Children

Dr. Amy Wong obtained her PhD at the University of Toronto studying the role of bone marrow-derived stem cells in airway regeneration. Prior to that she completed a Masters degree also at UofT in Cardiovascular sciences studying the role of extracellular matrix proteins in vascular remodeling and progenitor cell behavior. In 2009, upon completion of her PhD degree, she joined the laboratories of Drs. Janet Rossant and James Ellis as a postdoc, where she was one of the pioneers who developed a method to generate lung cells from human embryonic and induced pluripotent stem cells. This multi-lab collaborative work was published in Nature Biotechnology in 2012 and was detailed later in Nature Protocols in 2015. Now, Dr Wong is a Senior Research Associate in the lab of Dr. Janet Rossant and is interested in direct lineage conversion and using pluripotent stem cell-derived lung progenitors for 3D lung disease modeling and development.

On Janet

Who are your scientific idols?
Some of my earliest scientific idols were the Canadian heroes of stem cell biology: James Till, Ernest McCulloch and Charles LeBlond.

What's the focus of your current work?
Our current work is focused on generating renewable sources of airway lung epithelial-type cells for personalized drug screening in cystic fibrosis (CF).

What influenced you to pursue research in this field?
My long term interests lie in understanding early embryo development and how pluripotency arises. This led us to working on embryonic stem cells and iPS cells, and then working at SickKids led us to thinking about how we could apply our expertise to clinical problems in children. Interaction with member of the SickKids CF Centre focused our attention on cystic fibrosis.

What influenced you to become actively involved in the ethical discussion and Canadian/international policy around human embryonic stem cell research?
Scientists need to engage more with the public and take on issues where they can help explain the scientific underpinnings of ethical issues.

What's it like being a scientist in the Hospital for Sick Children?
It's an amazing place where scientists of all sorts - PhDs, MDs and allied health professionals - mix together and engage on research with the overarching goal of improving child health.

You've recently became the first female scientist to receive the prestigious Canada Gairdner Wightman Award. Do you have any message to early-career female scientists out there?
Persevere in your research, build a strong support structure in your outside life, and don't be afraid to take on new challenges.

On PSC Research

What advances do you hope the stem cell biology field will achieve in the next 5 years? See More
I see rapid progress to actual clinical translation of stem cell research into cell-based therapies across a variety of areas. Stem cells and their differentiated progeny, as well as transdifferentiated cells and organoids will be standard tools for exploring the underlying mechanisms of human disease and discovering new diagnostic tools and therapies.

There has been significant progress in recent years in directed differentiation of pluripotent cells across a variety of tissues. What do you see as being the biggest obstacles in generating PSC-derived cells that are functionally equivalent to their primary cell counterparts?
There is not enough knowledge about the normal in vivo processes.

Many hPSC-related protocols have proven to be difficult to transfer from lab to lab. Do you see a role for protocol and reagent standardization enabling effective collaboration and the ability to make cohesive contributions to the field at large?
Definitely - this is a big challenge.

There is a lot of research happening now about different states of pluripotency, particularly human naïve state, or ground state pluripotent stem cells. Where do you see this technology going?
Naïve state pluripotent stem cells are interesting basic biology and relevant to differences in embryo development between mouse and human. But it's probably not very influential in terms of regenerative medicine.

Do you see hiPSCs having an impact on the treatment of lung diseases in the future? What technical hurdles need to be overcome in order for hiPSC-based cellular therapies to become a reality?
Yes. Some of the technical hurdles include useful reagents for drug discovery and drug testing. It's still a long way from a cell therapy because the lung epithelium is very complex and the hierarchy is not well understood.

On STEMCELL Technologies Products

Has using STEMCELL's products made work in your lab easier?
Yes - good reliable reagents are vital to our experiments.

Are there products that you have found to be particularly useful in carrying out or optimizing your experiments? Can you describe your experience?
Stemdiff [STEMdiff™ Definitive Endoderm Kit] really helped our lung differentiation protocol. Please watch the webinar to learn more about its usage in our experiments.

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