The Age of Engineered Cells

Our cells are very versatile and complex machines, really an assemblage of many such machines. As researchers make inroads into understanding the details of the mechanisms, they will become ever more capable of manipulating and engineering cells. The earliest meaningful efforts here are focused on (a) trying to change the high level state of the cell, to turn an ordinary cell into a stem cell, for example, and (b) directing cells to undertake specific actions by issuing chemical signals, such as efforts to spur stem cells into greater feats of regeneration.

In the future, engineering cellular state and behavior will become a very broad technology platform indeed. Almost any part of the cell is open to change, enhancement, or outright replacement if fully understood. We couldn't possibly predict all of what will be accomplished here: engineered cells may be turned into medical instruments, for example, programmed to construct drugs and move through the body to where those drugs are needed. Entire classes of cells, such as immune system cells, may be retired to be replaced with more efficient versions. And so forth.

Here and now, however, this line of research is still just beginning. The cutting edge today is focused on infrastructural needs, such as low cost and reliable production of stem cells. Half the battle here is finding ways to build the tools of research cheaply enough to allow a much larger research community to join in - a hundred labs produce a far greater diversity of results than ten.

With that in mind, here are a couple of recent examples of new progress and discovery in stem cell engineering:

New method for generating human stem cells is remarkably efficient

The ability to efficiently generate patient-specific stem cells from differentiated cells and then reliably direct them to form specialized cells (like neurons or muscle) has tremendous therapeutic potential for replacing diseased or damaged tissues. However, despite some successes, there have been significant limitations associated with existing methods used to generate human induced pluripotent stem cells (iPSCs).


Dr. Rossi and colleagues did not take the standard approach to permanently alter the genome to achieve expression of protein factors known to reprogram adult cells into iPSCs. Instead, they developed synthetic modified messenger RNA molecules (which they termed "modified RNAs") that encoded the appropriate proteins but did not integrate into the cell's DNA.

Repeated administration of the modified RNAs resulted in robust expression of the reprogramming proteins in mature skin cells that were then converted to iPSCs with startling efficiency. "We weren't really expecting the modified RNAs to work so effectively, but the reprogramming efficiencies we observed with our approach were very high," says Dr. Rossi.

Use of RNA in place of gene alteration is a theme of late, and you should expect to see more of it in the future. Gene expression, the production of proteins from genetic blueprints, is a multi-step process: firstly, RNA is formed through transcription, and that RNA in turn produces the final protein product. If you introduce the appropriate RNA, then the genetic change is unnecessary, as the production of the protein picks up at a later stage. There are other advantages to working in RNA rather than gene therapy as well, such as easier control over turning a change on and off.

Researchers engineer adult stem cells that do not age

Biomedical researchers at the University at Buffalo have engineered adult stem cells that scientists can grow continuously in culture, a discovery that could speed development of cost-effective treatments for diseases including heart disease, diabetes, immune disorders and neurodegenerative diseases. ... the breakthrough overcomes a frustrating barrier to progress in the field of regenerative medicine: The difficulty of growing adult stem cells for clinical applications.

Because mesenchymal stem cells have a limited life span in laboratory cultures, scientists and doctors who use the cells in research and treatments must continuously obtain fresh samples from bone marrow donors, a process both expensive and time-consuming.


The cells that UB researchers modified show no signs of aging in culture, but otherwise appear to function as regular mesenchymal stem cells do - including by conferring therapeutic benefits in an animal study of heart disease. Despite their propensity to proliferate in the laboratory, MSC-Universal cells did not form tumors in animal testing.

This second item is a most interesting discovery: immortal cell populations exist in the germ line and in certain cancers, so immortality is clearly a characteristic that cells are capable of. But I don't think anyone was expecting to just flip a switch and have this show up cleanly and distinctly in other cell types. The most promising aspect of this research is that the cells seem otherwise normal, no more capable of causing havoc than an ordinary germ cell.

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