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An Interview with Dr. Krishanu Saha from the Whitehead Institute of Biomedical Research: On the invention of a new Synthetic Surface for the Cultivation of Human Stem cells for up to three months.

Scientists at MIT have developed a novel synthetic surface for the cultivation of human stem cells. The research team, led by Professors Robert Langer, Rudolf Jaenisch and Daniel G. Anderson, describes the new material in the Aug. 22 issue of Nature Materials. First authors of the paper are postdoctoral associates Krishanu Saha and Ying Mei. The new material was singled out of almost 500 polymers designed during the course of the study, and was found to be optimal after analysing  several chemical and physical properties of surfaces, including roughness, stiffness, and affinity for water that might play a role in stem cell growth. The new surface not only enabled Stem Cells to be grown for up to three months but also enabled harvesting of cells in the millions. Both of these attributes are very important to researchers as the in vitro culture of human Stem cells is fraught with difficulty. The surface also enables clonal growth of a stem cell allowing for easy selection of a particular cell with attributes of interest. As Researchers laud this important invention, Biotechwiz is proud to present an exclusive interview with Dr. Krishanu Saha, one of the authors of this seminal work. An excerpt of the interview is presented below:

Dr. Krishanu Saha

Dr. Krishanu Saha

Biotechwiz: Why did you feel the need to develop a new material for the growth of stem cells?

Dr. Krishanu Saha: When we started this work, there were only a handful of culturing materials that were used to grow human embryonic stem cells. Most of these materials included components from animal sources. These animal-derived components are problematic for any cell therapy applications envisioned with these cells, because such components utilized during cell culture can increase the risk of immune rejection when such cells are injected into a patient.  We therefore sought to explore whether a library of synthetic polymers coated with human-derived proteins could replace and improve on the conventional methods of growing human embryonic stem cells.

We also wanted to gain more molecular insight into how human embryonic stem cells grow outside of the body. Mouse embryonic stem cells have particular properties of cell growth and genetic manipulation that make them easier to work with in the lab.  We wondered whether we could devise better culture conditions for human embryonic stem cells by systematically exploring stem cell growth on a diverse set of polymeric materials.

BW: Can you elaborate a bit on the nature of this new surface that you have developed and what is the most unique feature of your invention according to you?

Dr. Saha: The new surfaces can be synthesized entirely from standard chemicals.  They utilize a particular chemistry that was not defined before this work to interact with a human protein, Vitronectin.  The most unique feature is that it can support the long-term culture of fully dissociated human embryonic stem cells as well as the recently ‘reprogrammed’ human induced pluripotent stem cells.

BW:  How soon do you think the research you have done will be available as a commercially viable product?

Dr. Saha: This question of technology transfer is a difficult one to predict. There are already a few commercial products based on other work with novel stem cell culture materials that was just published in May. So if we extrapolate from those cases, our work could be translated into products in less than a year.  I believe the MIT technology transfer office is dedicated to ensuring that the materials get widely used.

BW:  What is the trend your future research is likely to take?

Dr. Saha: I am generally interested in combining this work with recent advances in cellular reprogramming. Cellular reprogramming can produce embryonic stem cell-like cells called induced pluripotent stem (iPS) cells from virtually any human cell source, such as a blood sample or biopsy.  I believe there is a key role of materials and engineering to play in developing these iPS cells for disease modelling and regenerative medicine applications.

BW: Can you tell us about any one hurdle that bugged you the most during your work?

Dr. Saha: Finding common patterns in the material characteristics that controlled the growth of the human embryonic stem cells was challenging.  We had hundreds of polymers with lots of data about surface chemistry, stiffness, and roughness that needed to be sorted and globally analyzed. At times, this seemed tedious, but it is part of the research process.

Drew Endy

Drew Endy

Drew Endy is a forty- something Engineer. He has earned degrees in Civil, Environmental and Biochemical Engineering and today he is a faculty of the prestigious Stanford University. So, what else is new?  one might ask. Well, what is new is that his passion for building things is not limited to the sterile world of machines and electronic parts alone. Drew Andy wants to get down and dirty with Biology! “I build things, that’s what I do”, says this self- effacing man who has become the face of one of the newest kids on the technology block; Synthetic Biology. And what is this Synthetic Biology?

Wikipedia defines Synthetic Biology as follows: Synthetic biology is a new area of biological research that combines science and engineering in order to design and build (“synthesize”) novel biological functions and systems. A more technical definition states, “Synthetic biology refers to both:

  • The design and fabrication of biological components and systems that do not already exist in the natural world  &,
  • The re-design and fabrication of existing biological systems”.1

To make matters simple, Synthetic Biology aims to use the components of nature as building blocks to build hitherto non-existent systems. So, how is this approach supposed to be different from the current field of Genetic Engineering? Well, in the latter, scientists cut and chop pieces of DNA, the fundamental molecule of information in living systems, from different organisms and paste them together. The aim of this is to improve the existing system by augmentation with a desirable trait from another DNA molecule. So, we have the easily cultivable E. coli cell spliced with genes producing Human Insulin yielding virtual factories of this much-needed molecule. Or we have crop plants spliced with genes to increase their tolerance to salt or to improve their yield or size of the grain, all efforts to improve the existing quality of the plant.

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Plant tissue culture (PTC) is a term most biotechnologists are well-acquainted with. This technology exploits what is known as the totipotency of Plant cells. Totipotency is the inherent capacity of each and every living plant cell, whether it originates from a leaf or stem or root of a plant to be able to give rise to an entire plant on its own. In short, I don’t need a seed to grow a plant. If I can  extract a set of totipotent cells from a plant and give it the right set of nutrients, the right temperature and day-night cycle and of course an optimal cocktail of hormones (Plant growth promoting), I can grow a complete plant out of those few cells. So I excise a small portion of the plant (leaf, stem, node, root etc) which is called the explant and then after carefully treating it with the proper set of disinfectants (to get rid of contaminating microbes) I inoculate it into media (liquid or solid) and provide it with all optimal growth parameters. Within a reasonable period of time I should be able to obtain plantlets out of my original explant. This is a very simplistic explanation of plant tissue culture.

From the time Gautheret worked with encouraging results in the young field of PTC in 1934 and the problem of tissue culture of plant cells was definitely solved in 1939, independently by Gautheret, Nobécourt and White, the field has come a long way. With more than ten thousand researchers actively engaged in this field of research1 the technique has undergone massive changes in method and application. From the more academic applications of trying to demonstrate totipotency and wound healing effects to generation of entirely new plants with the view to transplanting them in fields, we have witnessed the growth of an important tool of biotechnology.

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