Lifeboat Foundation

Circa 2019

The evolution of micro and nanofabrication approaches significantly spurred the advancements of cardiac tissue engineering over the last decades. Engineering in the micro and nanoscale allows for the rebuilding of heart tissues using cardiomyocytes. The breakthrough of human induced pluripotent stem cells expanded this field rendering the development of human tissues from adult cells possible, thus avoiding the ethical issues of the usage of embryonic stem cells but also creating patient-specific human engineered tissues. In the case of the heart, the combination of cardiomyocytes derived from human induced pluripotent stem cells and micro/nano engineering devices gave rise to new therapeutic approaches of cardiac diseases. In this review, we survey the micro and nanofabrication methods used for cardiac tissue engineering, ranging from clean room-based patterning (such as photolithography and plasma etching) to electrospinning and additive manufacturing. Subsequently, we report on the main approaches of microfluidics for cardiac culture systems, the so-called “Heart on a Chip”, and we assess their efficacy for future development of cardiac disease modeling and drug screening platforms.

The way the team made the human–monkey embryo is similar to previous attempts at half-human chimeras.

Here’s how it goes. They used de-programmed, or “reverted,” human stem cells, called induced pluripotent stem cells (iPSCs). These cells often start from skin cells, and are chemically treated to revert to the stem cell stage, gaining back the superpower to grow into almost any type of cell: heart, lung, brain…you get the idea. The next step is preparing the monkey component, a fertilized and healthy monkey egg that develops for six days in a Petri dish. By this point, the embryo is ready for implantation into the uterus, which kicks off the whole development process.

This is where the chimera jab comes in. Using a tiny needle, the team injected each embryo with 25 human cells, and babied them for another day. “Until recently the experiment would have ended there,” wrote Drs. Hank Greely and Nita Farahany, two prominent bioethicists who wrote an accompanying expert take, but were not involved in the study.

While DNA provides the genetic recipe book for biological form and function, it is the job of the body’s proteins to carry out the complex commands dictated by DNA’s genetic code.

Stuart Lindsay, a researcher at the Biodesign Institute at ASU, has been at the forefront of efforts to improve rapid DNA sequencing and has more recently applied his talents to explore the much thornier problem of sequencing protein molecules, one molecule at a time.

In a new overview article, Lindsay’s efforts are described along with those of international colleagues, who are applying a variety of innovative strategies for protein sequencing at the single-cell, and even single-molecule level.

A research team from the University of Massachusetts Amherst has created an electronic microsystem that can intelligently respond to information inputs without any external energy input, much like a self-autonomous living organism. The microsystem is constructed from a novel type of electronics that can process ultralow electronic signals and incorporates a device that can generate electricity “out of thin air” from the ambient environment.

The groundbreaking research was published June 7 in the journal Nature Communications.

Jun Yao, an assistant professor in the electrical and computer engineering (ECE) and an adjunct professor in biomedical engineering, led the research with his longtime collaborator, Derek R. Lovley, a Distinguished Professor in microbiology.

Imagine you’re a fisherman living by a lake with a rowboat. Every day, you row out on the calm waters and life is good. But then your family grows, and you need more fish, so you go to the nearby river. Then, you realize you go farther and faster on the river. You can’t take your little rowboat out there—it’s not built for those currents. So, you learn everything you can about how rivers work and build a better boat. Life is good again…until you realize you need to go farther still, out on the ocean. But ocean rules are nothing like river rules. Now you have to learn how ocean currents work, and then design something even more advanced that can handle that new space.

Communication frequencies are just like those water currents. And the boats are just like the tools we build to communicate. The challenge is twofold: learning enough about the nature of each frequency and then engineering novel devices that will work within them. In a recent paper published in Proceedings of the IEEE, the flagship publication of the largest engineering society in the world, one USC Viterbi School of Engineering researcher has done just that for the next generation of cellular networks—6G.

Andy Molisch, professor of electrical and computer engineering at USC Viterbi and the holder of the Solomon Golomb—Andrew and Erna Viterbi Chair, together with colleagues from Lund University in Sweden, New Zealand Telecom, and King’s College London, explained that we have more options for communications at 6G frequency than previously thought. Think of it as something like early explorers suddenly discovering the gulf stream.

A new technology could dramatically improve the safety of lithium-ion batteries that operate with gas electrolytes at ultra-low temperatures. Nanoengineers at the University of California San Diego developed a separator—the part of the battery that serves as a barrier between the anode and cathode—that keeps the gas-based electrolytes in these batteries from vaporizing. This new separator could, in turn, help prevent the buildup of pressure inside the battery that leads to swelling and explosions.

“By trapping gas molecules, this separator can function as a stabilizer for volatile electrolytes,” said Zheng Chen, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering who led the study.

The new separator also boosted battery performance at ultra–low temperatures. Battery cells built with the new separator operated with a high capacity of 500 milliamp-hours per gram at-40 C, whereas those built with a commercial separator exhibited almost no capacity. The battery cells still exhibited high capacity even after sitting unused for two months—a promising sign that the new separator could also prolong shelf life, the researchers said.

Check out this short educational video in which I explain some super exciting research in the area of nanotechnology: gigadalton-scale DNA origami! I specifically discuss a journal article by Wagenbauer et al. titled “Gigadalton-scale shape-programmable DNA assemblies”.

Here, I explain an exciting nanotechnology paper “Gigadalton-scale shape-programmable DNA assemblies” (https://doi.org/10.1038/nature24651).

Continue reading “Gigadalton-scale DNA origami nanostructures explained” »

The latest from Calico. A bit technical.

Reprogramming of ordinary somatic cells into induced pluripotent stem cells (iPSCs) was initially thought to be a way to obtain all of the patient matched cells needed for tissue engineering or cell therapies. A great deal of work has gone towards realizing that goal over the past fifteen years or so; the research community isn’t there yet, but meaningful progress has taken place. Of late, another line of work has emerged, in that it might be possible to use partial reprogramming as a basis for therapy, delivering reprogramming factors into animals and humans in order to improve tissue function, without turning large numbers of somatic cells into iPSCs and thus risking cancer or loss of tissue structure and function.

Reprogramming triggers some of the same mechanisms of rejuvenation that operate in the developing embryo, removing epigenetic marks characteristic of aged tissues, and restoring youthful mitochondrial function. It cannot do much for forms of damage such as mutations to nuclear DNA or buildup of resilient metabolic waste, but the present feeling is there is nonetheless enough of a potential benefit to make it worth developing this approach to treatments for aging. Some groups have shown that partial reprogramming — via transient expression of reprogramming factors — can reverse functional losses in cells from aged tissues without making those cells lose their differentiated type. But this is a complicated business. Tissues are made up of many cell types, all of which can need subtly different approaches to safe reprogramming.

Today’s open access preprint is illustrative of the amount of work that lies ahead when it comes to the exploration of in vivo reprogramming. Different cell types behave quite differently, will require different recipes and approaches to reprogramming, different times of exposure, and so forth. It makes it very hard to envisage a near term therapy that operates much like present day gene therapies, meaning one vector and one cargo, as most tissues are comprised of many different cell types all mixed in together. On the other hand, the evidence to date, including that in the paper here, suggests that there are ways to create the desired rejuvenation of epigenetic patterns and mitochondrial function without the risk of somatic cells dedifferentiating into stem cells.

Continue reading “A Great Deal of Work Lies Ahead in the Development of In Vivo Reprogramming as a Therapy” »

The idea is simple: decades of research have found certain genes that seem to increase the chance of Alzheimer’s and other dementias. The numbers range over hundreds. Figuring out how each connects or influences another—if at all—takes years of research in individual labs. What if scientists unite, tap into a shared resource, and collectively solve the case of why Alzheimer’s occurs in the first place?

The initiative’s secret weapon is induced pluripotent stem cells, or iPSCs. Similar to most stem cells, they have the ability to transform into anything—a cellular genie, if you will. iPSCs are reborn from regular adult cells, such as skin cells. When transformed into a brain cell, however, they carry the original genes of their donor, meaning that they harbor the original person’s genetic legacy—for example, his or her chance of developing Alzheimer’s in the first place. What if we introduce Alzheimer’s-related genes into these reborn stem cells, and watch how they behave?

By studying these iPSCs, we might be able to follow clues that lead to the genetic causes of Alzheimer’s and other dementias—paving the road for gene therapies to nip them in the bud.