The Doctor Weighs In

by Dov Michaeli

Sometimes revolutionary developments come out of the most unexpected corners. There is new branch is medical research called regenerative medicine.

The “old” way of treating disease (which we are still practicing today) is through drugs that treat the consequences of the disease. For instance, anti-inflammatory drugs to treat arthritis, or statins to lower cholesterol through inhibition of its synthesis, or chemotherapeutic drugs to kill tumor cells.

The bold vision of investigators in the regenerative medicine field is to simply replace the ailing organ with a healthy one. I am not talking about transplantation; I am talking about stem cells that can be programmed to replace an injured muscle, a severed spinal cord, or damaged pancreatic beta cells that can no longer synthesize insulin. This is a breathtaking paradigm shift that promises to revolutionize the way medicine will be practiced in the not so distant future.

Out of left field

As our attention was riveted on “the big stuff” of stem cells, a barely noticed report, published in the February issue of The Archives of Dermatology (vol. 143, pp. 155-163, 2007), looked at the mode of action of a dermal filler used in cosmetic medicine to treat facial wrinkles. The report, by a group from the department of Dermatology at the University of Michigan, showed that contrary to the belief that the material (Restylane is made up of a substance called cross-linked hyaluronic acid) acted simply by physical expansion of the skin volume, it actually had a biological effect.

What is a wrinkle?

The skin is made up of a thin outer layer of cells called epidermis, and a much thicker layer called dermis. The bulk of the dermis is composed of a protein called collagen, as well as smaller amount jelly-like materials, hyaluronic acid being one of them. Collagen is synthesized by special skin cells called fibroblasts.

In a young person the fibroblasts have a stretched appearance and secrete copious amounts of the collagen, enough to make up for the continuous degradation of skin collagen by an enzyme called collagenase. In older people the fibroblasts become more relaxed and rounded, and secrete less collagen, not enough to counteract the losses due to the degradation by collagenase. Slowly but surely, enough collagen is removed, the dermal structure collapses, and we get the dreaded wrinkles.

What the investigators found is that the hyaluronic acid in Restylane caused the re-stretching of the fibroblasts, causing them to increase their synthesis of collagen. As a bonus, the material also reduced the activity of the enzyme collagenase. The key to achieving this effect was the repeated injection of the material, 6-12 months apart, until enough stretching of the fibroblasts took place. How long would this effect last? This is still unknown, but the thought is that as long as the injected material is present the fibroblasts would remain stretched and synthesize more collagen.

Why is it exciting?

First, if confirmed, it promises to make us look young forever, or at least as long as we live. Isn’t that what all aging boomers look for?  But more importantly, here is the first realization of the regenerative medicine dream: use of the body’s own cells to regenerate damaged organs.

I love this study, because out of the limelight of the titanic stem cell struggles a relatively unknown group of dermatologists found a simple, and vastly more practical solution then stem cells to rejuvenation the sagging skin—simply stretch the old fibroblasts.   The study used Restylane only because it was started before a similar product, Juvéderm, was available. In my estimation, both products should work equally well; but the proof will require another study.

Here is another interesting aspect of progress in medicine. The material was originally intended as a physical filler; nobody had any grandiose thoughts about profound biological effects. After all, collagen itself was used as a filler to treat wrinkles, and indeed that is all it was—a filler, which degraded with time.

Hyaluronic acid, quite unexpectedly, opened new avenues for research in tissue regeneration. Would we be able soon to grow pre-existing brain neurons in Parkinson’s or Alzheimer’s patients by simply injecting ‘brain filling material’? If you asked this question a few months ago you’d be laughed out of the room. It is now totally plausible. Isn’t that exciting?

Dov Michaeli MD Ph.D. is in the biotech industry, engaged in drug development.