StemCell Therapy

Ok. Bits of this film are a little grim, but its worth it. Well, go on then!

Amazing right? And yes, its real! I have to admit I double-checked the date when my friend forwarded me the National Geographic link, but April first it was not. Researchers at the University of Pittsburgs McGowan Institute for Regenerative Medicine have made the skin cell spray gun a very real, very effective treatment for burn victims.

So how does it work? At its core, this treatment relies on the unique properties of stem cells, so thats where Ill begin. Stem cells

Stem cells have fascinated biologists for years. They are unique amongst all other cells of the body in two ways; their capacity for self-renewal, and their ability to give rise to many different cell types.

Embryonic stem cells, which frequently (and controversially) make the news, are derived from a developing fetus. They are the ultimate in stem cell-iness because they have the potential to direct the development of an entire organism. This means that they contain all the information need to make muscles, nerves, eyes etc. And naturally this pluripotency (from the Latin pluri meaning many, and potency or potential) seemed like a fantastic quality for biologist to understand. Not only were there fundamental developmental principles to be learned, the medical applications were endless. However, glaring ethical issues arose regarding the taking of a life to save a life (that I wont get into here) that have resulted in the stringent regulation of embryonic stem cell research.

And so researchers turned to adult stem cells. While adult stem cells are not as versatile as embryonic stem cells, they do have the potential to direct the development of certain cell lineages. For example hematopoietic stem cells, which reside in your bone marrow, can divide asymmetrically into all the different cells of your blood. Similarly, all the different layers of your skin have ancestral skin stem cells.

Research into embryonic stem cells resulted in the identification of certain genes that were expressed in, and required by, stem cells. In 2006, a Japanese group generated the first induced pluripotent stem cells. Since then much work has gone into understanding the potential of these induced stem cells. However due to genetic manipulation and lack of correct genomic imprinting (small chemical modifications in our DNA that are laid down in the egg), induced pluripotent stem cells have the unfortunate ability to become cancerous. As detailed in a recent paper in Cell however, while these cells are not yet ready for the clinic, this should not prevent them from being used in a laboratory setting. Stem cells as a treatment

Bone marrow transplantation was the first example of a stem cell therapy. In 1959 the French surgeon Georges Math treated six nuclear power plant workers who had been so severely irradiated that their hematopoietic stem cell populations had been destroyed. The procedure has since been used with great success in the treatment of leukemia.

As with all transplants, the potential of the host rejecting the donor tissue exists. This rejection occurs because of subtle cellular differences between each and every one of us. Our immune system recognizes these differences as foreign, much as it would any other pathogenic invader, and mounts a formidable defense. With the development of tissue typing procedures and administration of immunosuppressive drugs, transplant rejection has significantly decreased.

By far the best way of avoiding rejection, however, is to transplant the recipients own tissue. In certain procedures, such as small areas of skin grafting, such auto-grafting is a viable option. But in others, such as in the case of organ transplantation, it is not. And this is where stem cells can sweep in and save the day.

Tissues in dishes

We have long had the capacity to grow cells in vitro (which literally means within a glass). Bacterial cells grow happily in test tubes when provided with simple nutrients and an incubator, as do yeast cells. Mammalian cells are a little more difficult to deal with, but again we have been culturing them in the lab for over a hundred years. All they require is a container to grow in that protects them from infection, liquid media containing essential amino acids and other nutrients, and a warm humid chamber in which to grow.

I am however talking about growing one type of cell at a time. Growing an organized tissue presents a far greater challenge. Not only do the cells have to grow and divide, they have to interact with one another and take on specialized roles within the tissue. Normally in our bodies external forces and small molecules send signals between cells that direct this process. Culturing a tissue in vitro requires a significant understanding of how the tissue forms, and an ability to isolate the stem cells from which the tissue is derived.

In the case of transplantation, the stem cells can be derived from the patient who will receive the cultured tissue, thus removing the chance of complications arising due to donor incompatibility. As you saw in the video, skin grafts have been performed in this way for quite some time, but with variable success.

The skin gun

And this is of course where the genius of the skin gun, and its inventor Joerg C. Gerlach, comes in; it bypasses the need for the in vitro tissue culturing. Skin stem cells that had been destroyed in the burn are replaced, and then the tissue is allowed to heal. As in the case of tissue culture in a lab, these cells require a sterile and nutrient rich environment to thrive. After the initial spraying, the wound is covered with a dressing that contains a synthetic circulatory system that brings nutrients to the infant skin and removes any toxins and waste products.

The speed and effectiveness of this treatment is out of this world. The guy in the video didnt even have a scar after his treatment. Perhaps the spray gun as a means of stem cell delivery is unique to skin regeneration, but there are a couple of features that should be transferable to other transplants, particularly the ability to enrich a patients own stem cells and re-apply them to damaged tissue. This will likely be advanced from burgeoning knowledge on where adult stem cells reside in our body, in so-called stem cell niches. With skin stem cell therapy now a reality, what will be next? Will we be able to re-grow more complex organs such as kidneys? Or will we be able to harvest healthy stem cells from a niche before a disease such as leukemia becomes debilitating? What do you think?

Bock, C., Kiskinis, E., Verstappen, G., Gu, H., Boulting, G., Smith, Z., Ziller, M., Croft, G., Amoroso, M., & Oakley, D. (2011). Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines Cell, 144 (3), 439-452 DOI: 10.1016/j.cell.2010.12.032

Hi Peter,

Thanks for the links. I should probably have pointed out in my article that this idea is not totally novel. The Australian plastic surgeon Dr. Fiona Wood has been using a similar technique for close to a decade. She has since started a company, http://www.avitamedical.com/index.php?ob=1&id=37. The technique was used extensively to treat burn victims of the Bali bombings in 2002. The recent development of the stem cell gun has basically increased the efficiency of the system, reduced damage caused to the stem cells during spraying, and made the technique more user friendly in a hospital setting.

However, I searched and searched and there is no Nature paper, which honestly baffled me too.

I was happy to see in that link that a clinical trial is in the works. Hopefully from that some concrete data can be collected as to the precise efficacy of the cell spray system, as well as a peer-reviewed article on the subject. It seems to me that burn experts are divided on the merit or value of the treatment. In my opinion the only way a consensus can be reached is through a thorough, scientific and transparent trial. But should the therapy prove itself in that setting, I think it is a fantastic advancement in the therapeutic use of adult stem cells.

Would this work on a aged skin, skin damaged other than fire, frostbite, gangrene, cancer, etc?

What about those sunbathers with leathery type of skin?

Thanks

Ha I like your idea about the leathery sun-worshipers! I think stem cell therapy like this has potential for aiding wound healing, ie where large amounts of skin have had to be removed. But I do not think it could help adult skin thats already present. Youd have to remove the whole leathery mess and start againa new era of cosmetic surgery?

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Spray on some stem cells and grow your own skin! | Katie PhD

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