NYSCF sat down with Principal Investigator Dr. Danny Freytes, to talk about his path to bioengineering and stem cell research, and his recent paper in Journal of Tissue Engineering and Regenerative Medicine, which paves the path toward making cellular patches for damaged hearts.
Tell us about your background and how you started in research.
I started out as a mechanical engineering undergraduate at Purdue University. Back then there was no biomedical engineering program at Purdue and I wanted to work in the medical sciences. I also enjoyed engineering and math, so biomedical engineering was a good fit. At that time, there was a lot of talk about biomechanics and hip replacements and that got me interested in the field. Since there was no biomedical engineering program, I made my own by taking pre-med courses and involved myself in the Hillenbrand Biomedical Engineering Center at Purdue University. During that time, Dr. Badylak and Dr. Geddes introduced me to tissue engineering. Dr. Badylak took me in as an undergraduate student and began working on tissue engineered patches.
Being part of the Tissue Engineering field made me want to pursue a PhD instead of an MD. I was thinking of going to medical school, but I liked research enough that I stuck with it. I finished a master’s degree at Purdue. During that time my mentor, moved to the University of Pittsburgh so I followed him to Pittsburgh for my doctoral work. My [thesis] combined naturally occurring biomaterials with synthetics to create new forms of bioactive materials for implantation.
How did you find your way to NYSCF?
When I was finishing my PhD, my wife got a job here in NJ so I followed her, and I started looking for a post-doctoral position in the area. I was fortunate enough to do my postdoctoral training at Columbia [University Medical Center] in Dr. Gordana Vunjak-Novakovic’s laboratory. During this time, I applied for a fellow-to-faculty award from NYSTEM [New York State Stem Cell Science], which gave me two extra years as a postdoc and also provided funding for three more years as an independent investigator. It just so happened that around that time there was an opening for a Principal Investigator position at NYSCF. I learned about NYSCF’s work and vision, I applied for the position, and here I am.
How did stem cells first figure into your work?
When I started my PhD, stem cell work was beginning to get attention in the sense that very few people were working with them and most people were doing progenitor-type [adult stem cell] work. Once I got to Gordana’s lab, I got introduced into embryonic stem cell research and that was how I got involved in the stem cell field.
[Stem cells] gave us the tools we needed as engineers to do our job. It wasn't just that they were exciting; we just needed them to make tissues. I was working on a couple of projects and one of them was in cardiac tissue engineering and you need cardiac cells to create cardiac tissue replacements. Back then there was a little bit of excitement around adult mesenchymal stem cells and it was thought they might be able to differentiate into cardiac cells. But, people slowly started figuring out that it wasn't necessarily the case. (There's still a little bit of controversy out there whether or not that's true.) Regardless, you need the tools and the building blocks. For me, as an engineer, it was super cool that we could get those types of cells using pluripotent stem cells (i.e. embryonic and iPSCs).
Does the NYSCF environment help you advance your research?
The nice thing about NYSCF is the fact that everything is consolidated into one larger effort. So, from a scientific point of view, having multiple disciplines working side-by-side and having the equipment and the facilities to do the research makes a huge difference. You can focus on the work instead of spending time figuring out the logistics of how to do it. You can just do it. Also, the mentality of allowing you to pursue high-risk, but high-reward research and innovative ideas without having to worry too much about funding makes you pursue real cutting edge research.
What does that look like in the NYSCF lab, “having multiple disciplines working side-by-side”?
The fact that one day I’m working on cardiac tissue engineering projects and the next day I’m working on a larynx project studying biomaterials — I have a pretty big range of interests that I can explore. NYSCF is a great environment to pursue your research interests.
What is the major overarching goal of your current cardiac research?
I would say that we're looking at something that most people are ignoring. I can do research that is not necessarily comfortable to do because it could backfire, but it's something that we feel needs to be done in order to take this technology to the clinic. My research, especially the cardiac work, tries to develop in vitro models using human cells to study how the potential repair cells will interact with the host-tissue. Right now we’re very dependent on animal work, and we're neglecting human physiology. We're setting up the building blocks and setting up the path for having in vitro testing platforms that can be used to test engineered constructs. We will find out if our design will survive an infarct [heart attack] or survive the actual surgical procedure. It won't be perfect, but at least it will provide an indication if we're on the right track or if further tweaks are required.
Right now the process takes too long because you always have to go to an animal model. The animal always has to be immunosuppressed; it’s often a non-physiological environment. Obviously, it's impossible to recapitulate everything that the body's doing, but if we start with simple systems, little by little, we will find important things that we can mimic and then take advantage of it during the testing phase.
How far are we from making this cardiac patch a reality — in laboratories? Clinics?
We're getting closer. People have to remember that maybe seven years ago we didn't have living human cardiac cells and all of a sudden we have a plethora of cardiac cells that spontaneously beat in the lab available to us. We're advancing very rapidly. A lot of people are working on this problem and things are coming together in a way that we should have a tissue-engineered therapy very soon. We're getting all the constituents, all the parts we need, little by little. Exact timing depends on funding, and regulation. I hope we see a tissue-engineered therapy within my lifetime.
This interview has been condensed and edited for clarity.
For the first time, a team of scientists at Columbia University Medical Center, including NYSCF – Druckenmiller Fellow alumnus Sarah Huang, MD, PhD, MPH, has successfully transformed human induced pluripotent stem (iPS) cells into functional human lung cells. This advance in stem cell science, supported by the NYSCF – Druckenmiller fellowship, has significant potential for modeling lung diseases, screening new drug candidates, studying human lung development, and, ultimately, for generating new lung tissue for transplantation.
Counter to the prevailing theory that beta cells die-off in Type 2 diabetes patients, NYSCF – Druckenmiller Fellow and postdoctoral research scientist at Columbia University Medical Center Chutima Talchai, PhD, is co-author on a paper in Cell that suggests these insulin-producing cells de-differentiate. Employing cellular lineage tracking, Dr. Talchai and her colleagues followed beta cells in Type 2 diabetic mice models. They discovered that these cells reverted to an immature state, rendered unable to produce insulin. These results could inform how diabetes is treated by identifying an agent to help re-differentiate these affected cells.
Dieter Egli, PhD, a NYSCF Senior Research Fellow, is co-author on a paper published in the August 19th edition of Nature Genetics, a study conducted in collaboration with the research group of Alex Meissner, PhD, of Harvard University. They studied how the mouse egg erases methylation marks on DNA that are specific to specialized adult cells yet differ in comparison to embryonic stem cells. These methylation marks are thought to be a major barrier in the reprogramming of a specialized cell to a stem cell. Within twelve days after nuclear transfer, they found that regulatory regions of genes were demethylated while repetitive DNA sequences remained methylated. This finding suggests that the egg contains factors that mediate the rapid and specific demethylation of genes, which may be important for development. Thereby, this work elucidates the potential of oocytes to reprogram specialized cells into stem cells.
At the Alzheimer’s Association International Conference this past July, Andrew Sproul, PhD, a NYSCF Postdoctoral Associate, presented NYSCF’s latest efforts to understand Alzheimer’s disease. They have generated relevant induced pluripotent stem (iPS) cell models from AD patients and well relatives that were then differentiated into cholinergic neurons. Other efforts in the generation of human iPS cell disease models include cortical neurons from Down’s syndrome patients and the creation of cell lines from ALS patients. These iPS lines reveal the underlying biology that animal models do not.