Keloids Be Gone? Using Biologic Therapies in the Treatment of Scar Overgrowth

Biologics

biologic therapies
Keloid scars can be especially disfiguring; however, biologic therapies could result in more effective treatments.
Image source: Flickr user Milos Milosevic

The most innocuous of scrapes can become the ugliest of scars and the worst among them tend to be keloid scars, but why? And how can this occurrence be prevented? Scar formation is a natural part of the healing process in which fibrous tissue replaces normal skin after injury. Composed of the same protein found in tissue (collagen), the actual fiber composition (instead of random basketweave structures, the collagen in scars is aligned in one direction) is where the difference emerges.1

But even scars fall within a grading system, and among them, keloid scars can be the most visible and aggressive. Typically seen in people of African, Asian or Hispanic descent, keloid scars are “thick, rounded, irregular clusters of scar tissue that grow at the site of a wound on the skin, but beyond the edges of the wound.”2 Current treatment for keloid scars include steroid injections, cryotherapy and surgery; however, these scars can often recur and treatments are not universally helpful to patients.3 Fortunately, new biologic therapies might form the link between scars and effective treatment.

How Biologic Therapies Can Pave the Way for Keloid Scar Treatment

Despite our limited knowledge of keloid formation, biologic therapies could still reinvigorate the limited therapeutic options for people suffering with extensive scars. These therapies should address one or both of the following areas:

Limit scar expansion: One of the most visible components of keloid formation is their ability to spread outside the original injury site. Biologic therapies could be designed that inhibit stem cell growth or growth factors within the scar that can lead to its spread. Aspirin has been known to inhibit the growth of mesenchymal stem cells and biologic therapies could behave similarly with human keloid fibroblasts. Alternatively, new studies have shown that the transplantation of mesenchymal stem cells can significantly decrease tissue fibrosis by activating the activity of the transforming growth factor-beta 3 (TGF-B3).4

Other molecular agents might need to be inhibited in order to limit the activity of human keloid fibroblasts. For example, TGF-B1 is synthesized by T-cells and is present at very large levels in the extracellular environment after injury. When TGF-B1 binds to its receptors, various signaling pathways are activated, including collagen-producing factors.5 Where biologic therapies to stimulate TGF-B3 should be considered, they should be used in conjunction with those that suppress TGF-B1. It is important to consider the various ways that stem cell therapy, in combination with the inhibition of certain growth signaling pathways in keloid fibroblasts, could abolish the formation of keloid scars if used shortly after injury.

Inhibiting inflammatory pathways: Inflammatory pathways are very important in the generation of scars. When normal tissue is injured, these pathways are activated and macrophages, T- and B- cells, and other immune system molecules, such as chemokines, are recruited to the site. Chronic inflammation can result in a steady pool of profibrotic cells, leading to fibrosis. Biologic therapies targeted against T and B lymphocytes are another one way to limit this chronic inflammation by arresting their cell division and thus preventing the site from being pushed into an “inflamed” state. Still, such therapies would have to be site directed with short half-lives to prevent them from diffusing into other locations in the body.

Other therapies could include limiting the expression of interferon-gamma, which induces an overexpression of certain proinflammatory molecules. This may involve using biologic therapies to limit the extent of factors involved in creating hypoxic and oxidative stress in tissue.

Now, there are many opportunities for researchers to uncover new biologic therapies for keloid scars. Such therapies could dramatically expand the numbers of people eligible for certain types of surgeries, as well as our basic understanding of skin biology. To leverage this information into products, specialized software can be utilized to bridge the gap between scientific knowledge and the development of new therapies. For example, in developing antibodies against immune system components, researchers must be able to accumulate extensive amounts of sequencing data. Additionally, various experiments for binding activities or efficacy studies must be carried out with drug candidates. Instead of deriving an entire experiment from scratch, using software that allows easy retrieval of scientific data can enable researchers to modify past experiments, reduce experimental error and leverage previously gained knowledge to accelerate time to market. Software such as BIOVIA Discovery Studio offers all of these benefits and more by providing a means to save, modify and ultimately automate various processes.

Understanding how cells respond to certain treatments is another component of data management that requires that a research institution retain and document the effects of a variety of treatments on keloid-like cells. The massive effort and organization on the part of a research team underscores the importance of relying on a software system that can ensure no data is lost.

The BIOVIA Biologics Solution offers essential technology that can assist your company in developing the newest therapies for keloids or numerous other biological challenges. To learn more about the Biologics Solution and how we can help you, please contact us today.

  1. “Mathematical Modelling of Scar Tissue,” http://www.macs.hw.ac.uk/~jas/researchinterests/scartissueformation.html
  2. “Conditions and Treatments: Scar,” 2009, http://www.dermatology.columbia.edu/conditions/scars.html
  3. “New Keloid Research Raises Hope for Future Treatments,” September 7, 2014, http://www.enttoday.org/article/new-keloid-research-raises-hope-for-future-treatments/?singlepage=1
  4. “Mesenchymal stem cells suppress fibroblast proliferation and reduce skin fibrosis through a TGF-B3-dependent activation,” March 2015, http://www.ncbi.nlm.nih.gov/pubmed/25858630
  5. “Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough,” July 14, 2014, http://www.hindawi.com/journals/sci/2014/340257/

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