Some publicity materials are presently doing the (late) rounds for a January review of progress in tissue engineering over the course of 2012. The review paper is open access, so I'm assuming that this is the standard process of picking a paper at some point after it is published and allowing open access for a while to draw some attention to the journal in question. Still, it's an interesting read, providing a perspective from inside the field on what is actually important enough to mention.

The merging of tissue engineering and regenerative medicine (TERM) forms an enormously broad, energetic, and important field of medical research. Not a week goes by without something new and vital happening in a regenerative medicine laboratory somewhere in the world, and vast sums of money flow into advancing the state of the art. Arbitrary tissues and organ structures grown from a patient's own cells are not so far ahead in the future now, and neither are ways to coerce the body to rebuild itself from the inside out. There is a certainly a sense of excitement among those involved.

Tissue Engineering and Regenerative Medicine: Recent Innovations and the Transition to Translation

The first challenge in conducting this review was the sheer number of recent publications in the TERM field. [The] number of TERM articles continues to rise with nearly 4000 original articles published in 2010, compared to a mere 360 a decade earlier. This can be partially attributed to the increasing use of the same common terminology, particularly for the more recent "regenerative medicine." Still, there is no doubt that our field is expanding and capturing a larger portion of the work done across the biomedical sciences.

Many seemingly discordant lines of research have now become intertwined in TERM and constitute the fabric of our field, with these concepts arising from the blurring of boundaries between traditional disciplines. While this point is sometimes easy to forget, much of what we now consider commonplace in TERM was only a short time ago separated by barriers of dogma and discipline. As these lines continue to blur, and multi-disciplinary research becomes more the rule than the exception, our field is experiencing tremendous growth.

The pace of growth is now so fast that it impossible for most of us to keep up with the field as a whole, or even a small subset of it. For example, a TERM search specific to "cartilage" returns more than 450 articles published in 2011 alone, meaning that one would need to read more than one article per day just to stay abreast of this small portion of the TERM terrain.

We found considerable innovation in a number of traditional TERM fields, but also new ideas that are beginning to take hold in emerging focal areas. For instance, in the realm of tissue replacement, we are now seeing not just scaffolds of ever-increasing complexity derived from standard engineering methods, but also complex scaffolds predicated on natural designs (and native tissues themselves, once decellularized). In the broader field of regenerative medicine, we are seeing developmental biology begin to address not just the formation of tissues, but the specific role that endogenous stem cells play in both generative and regenerative processes. Integrating these basic science findings with novel materials that specifically recruit endogenous populations may provide a next wave in smart biomaterials for tissue repair. Likewise, new cell sources, most prominently iPSCs, have come to the fore, making autologous cell-based therapies for any tissue a real possibility.

Finally, our objective screen showed that ours is truly a translational field, and that TERM advances are being reduced to clinical practice at an ever-increasing rate. [Both] the quantitative nature of these outcome measures and levels of evidence in support of these applications are advancing as well. Together, these advances are now beginning to change the lives of small subsets of the population, and in the future, these novel approaches will be able to address a host of diseases and instances of tissue degeneration that were heretofore untreatable.

Source:
http://www.fightaging.org/archives/2013/03/a-late-tissue-engineering-year-in-review-for-2012.php

Metformin, used as a treatment for diabetes, is a weak candidate for a calorie restriction mimetic drug, one that causes some of the same metabolic changes (and thus hopefully health and longevity benefits) as calorie restriction. The evidence for health and longevity benefits actually resulting from this usage is mixed and debatable, however; certainly nowhere near as clear as for, say, rapamycin. Here researchers propose that metfomin's method of action stems in part from suppressing chronic inflammation, which is known to contribute to the progression of age-related frailty and disease:

[Researchers] found that the antidiabetic drug metformin reduces the production of inflammatory cytokines that normally activate the immune system, but if overproduced can lead to pathological inflammation, a condition that both damages tissues in aging and favors tumor growth. Cells normally secrete these inflammatory cytokines when they need to mount an immune response to infection, but chronic production of these same cytokines can also cause cells to age. Such chronic inflammation can be induced, for example by smoking, and old cells are particular proficient at making and releasing cytokines.

"We were surprised by our finding that metformin could prevent the production of inflammatory cytokines by old cells. The genes that code for cytokines are normal, but a protein that normally triggers their activation called NF-kB can't reach them in the cell nucleus in metformin treated cells. We also found that metformin does not exert its effects through a pathway commonly thought to mediate its antidiabetic effects. We have suspected that metformin acts in different ways on different pathways to cause effects on aging and cancer. Our studies now point to one mechanism."

Link: http://www.sciencedaily.com/releases/2013/03/130327093604.htm

Source:
http://www.fightaging.org/archives/2013/03/metformin-may-act-to-reduce-chronic-inflammation.php

All commonalities in cancer are interesting, as part of the high cost of dealing with cancer is based on the many, many different varieties and the great variability of its biochemistry even between individual tumors. Anything that is common between many types of cancer and between tumors offers a possibility of a lower-cost and broader therapy. The cell surface marker CD47 has shown up of late as a possible commonality, and work continues to see whether a therapy can be built on this:

A decade ago, [researchers] discovered that leukemia cells produce higher levels of a protein called CD47 than do healthy cells. CD47 [is] also displayed on healthy blood cells; it's a marker that blocks the immune system from destroying them as they circulate. Cancers take advantage of this flag to trick the immune system into ignoring them. In the past few years, [researchers] showed that blocking CD47 with an antibody cured some cases of lymphomas and leukemias in mice by stimulating the immune system to recognize the cancer cells as invaders. Now, [researchers] have shown that the CD47-blocking antibody may have a far wider impact than just blood cancers.

"What we've shown is that CD47 isn't just important on leukemias and lymphomas. It's on every single human primary tumor that we tested." Moreover, [the scientists] found that cancer cells always had higher levels of CD47 than did healthy cells. How much CD47 a tumor made could predict the survival odds of a patient. To determine whether blocking CD47 was beneficial, the scientists exposed tumor cells to macrophages, a type of immune cell, and anti-CD47 molecules in petri dishes. Without the drug, the macrophages ignored the cancerous cells. But when the CD47 was [blocked], the macrophages engulfed and destroyed cancer cells from all tumor types.

Next, the team transplanted human tumors into the feet of mice, where tumors can be easily monitored. When they treated the rodents with anti-CD47, the tumors shrank and did not spread to the rest of the body. In mice given human bladder cancer tumors, for example, 10 of 10 untreated mice had cancer that spread to their lymph nodes. Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer. Moreover, the implanted tumor often got smaller after treatment - colon cancers transplanted into the mice shrank to less than one-third of their original size, on average.

Link: http://news.sciencemag.org/sciencenow/2012/03/one-drug-to-shrink-all-tumors.html

Source:
http://www.fightaging.org/archives/2013/03/more-on-cd47-as-a-potentially-broad-cancer-therapy-target.php

An interesting piece on the use of scaffold materials to guide regrowth in regenerative medicine:

A research group [is] weaving nanoscale nerve-guide scaffolds from a mixture of natural chitosan and an industrial polyester polymer, using a process called electrospinning. The raw materials are dissolved in solvents and placed into a syringe, the needle of which is attached to a high-voltage supply. Charged liquid is then expelled from the needle towards an earthed collector plate. Like a spark between a cloud and a lightning conductor, the liquid stretches out to the collector, and the molecules within it form into a solid but incredibly thin thread.

The resulting minuscule fibres accrete into a dense mesh whose texture is similar to that of the body's own connective tissue. In laboratory tests, prototype nerve guides built from this nanomaterial sustained the growth of new neural cells, produced no immune reactions and were much stronger and more flexible than commercial collagen tubes. By adjusting the electrospinning process, the orientation of the nanofibres can be controlled to build scaffolds suitable for cultivating cells that need precise alignment, such as elongated muscle fibres and heart tissue.

Link: http://www.economist.com/news/technology-quarterly/21573056-biomedical-technology-tiny-forms-scaffolding-combining-biological-and-synthetic

Source:
http://www.fightaging.org/archives/2013/03/on-nanoscale-featured-scaffolds-in-regenerative-medicine.php