I'd wager that the future of cell therapy probably won't involve much in the way of cell transplants, not even those created from the patient's own tissues. Instead it will be based on instructing existing cell populations in the body to take specific actions - progress here will proceed at a pace determined by how well researchers can catalog and understand the enormously complex networks of cell signaling that exists in every tissue type.

Even though there is a long way to go yet in creating that catalog, a range of possible therapies are already under investigation based on what is presently understood of controlling cell behavior. There is certainly no shortage of methods for changing the cell and its environment - only a shortage in knowing which of the million levers to pull and dials to set in order to achieve the desired result with minimal side-effects. Consider that a cell is a collection of machines built out of proteins, and the controlling mechanisms are driven by the presence and levels of yet more proteins: any technique that manipulates the level of a certain protein can be used to potentially good effect. So there is plain old gene therapy to make cells produce more of a protein encoded by a specific gene. There is RNA interference to block a specific protein. There are all sorts of other ways to tinker with how much of a specific protein is produced from the blueprint of a specific gene at a given time: gene expression is a process of many intricate stages, and the research community can presently accurately target most of them, provided the time is put in.

So all this said, we see technology demonstrations like the one noted below: no transplants, just instructing cells to do something different.

Gene therapy reprograms scar tissue in damaged hearts into healthy heart muscle

A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect. "The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting. The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle."

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, [researchers] transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material.

The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. [The] hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.

There will be a lot more of this sort of thing going on in the years ahead.

Source:
http://www.fightaging.org/archives/2013/01/instructing-scar-tissue-to-change-itself-into-healthy-tissue.php

Recommendation and review posted by Fredricko

This research illustrates one of the many challenges associated with untangling genetic contributions to longevity; some of those genes affect personality traits that are also known to correlate with longevity:

A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life. [This] derivative of a dopamine-receptor gene - called the DRD4 7R allele - appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.

The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals' reactivity to their environment.

People who carry this variant gene [seem] to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors. "While the genetic variant may not directly influence longevity, it is associated with personality traits that have been shown to be important for living a longer, healthier life. It's been well documented that the more you're involved with social and physical activities, the more likely you'll live longer. It could be as simple as that."

Link: http://news.uci.edu/press-releases/dopamine-receptor-gene-variant-linked-to-human-longevity/

Source:
http://www.fightaging.org/archives/2013/01/dopamine-receptor-variant-associated-with-longevity.php

Recommendation and review posted by Fredricko

Uncoupling proteins affect mitochondrial function, altering the balance of energy going to heat versus building ATP molecules to store it for use elsewhere. Like a range of other mitochondrial manipulations, altering levels of uncoupling proteins can extend life in laboratory animals, and here researchers suggest this works via hormesis, causing just enough damage to spur repair mechanisms to greater ongoing effects for a net overall gain:

Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria considerably increases lifespan in high fat diet fed UCP1 transgenic (TG) mice in comparison to wildtype (WT).

In order to clarify the underlying mechanisms we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low fat and high fat fed mice. TG mice [showed] elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress protective heat shock protein 25.

We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. All together our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23277187

Source:
http://www.fightaging.org/archives/2013/01/ucp1-extends-longevity-via-hormesis.php

Recommendation and review posted by Fredricko