I’d like to make an unusual proposition. It’s occurred to me that our bodies are kind of snobs.
Personality aside, our bodies are extremely particular. They reject tons of bacteria and viruses, while accepting others. They reject foreign tissues but can sometimes be coaxed into accepting them when bribed with medications. I suppose you could simply call it evolution, but figuring out who makes it into the elitist club that is our bodies is, nevertheless, one of the fundamental challenges of tissue engineering and transplant science.
As I’ve commented at length before, for an engineered graft to be usefully incorporated, it must 1) not be attacked by the immune system and 2) be successfully vascularized. These same principles apply toward the field of biomaterials, where non-cellular grafts are implanted into the body at the hopes that they will become cellularized, remodeled, and integrated with the body as a whole.
If you think about it, for a synthetic material to become part of a person, it must have pretty good connections pulling some strings.
For this reason, I am incredibly impressed with a paper in this month’s issue of Biomaterials. In it, Dr. Kara Spiller, currently an assistant professor at Drexel University, helps delineate the string of signals that leads to angiogenesis (i.e. new blood vessel growth) and vascularization of collagen scaffolds. Her paper specifically focuses on macrophages, a cell type that seems to carry a lot of weight in terms of the vascularization process.
It turns out that when a synthetic graft is implanted, it stimulates an inflammatory response, which involves several different types of macrophages (M1, M2a, M2c etc.). Traditionally, it has been thought that only certain subtypes of these macrophages have been influential in terms of promoting angiogenesis; however, their precise roles have been poorly understood. Dr. Spiller’s work abolishes the idea that it is only one specific macrophage type that is pro-angiogenic, and instead demonstrates that all have a unique message, which when timed properly, leads to vascularization of implanted biomaterials.
By better understanding what defines the different subsets of macrophages and which proteins they release to spread their message, we may be able to better control a patient’s response to a biomaterial-based graft in the clinic, as well as the development of vascularized tissue-engineered grafts in the lab. “The more we learn about macrophages, the more we realize that they’re at the centre of everything — from repair to regeneration to disease,” says Dr. Spiller. “If we can control their behavior, we can potentially control everything else.” Either way, macrophage biology is becoming a hot topic in numerous fields including wound healing, obesity, autoimmune diseases, and cancer.
While inclusion criteria for our bodies may always remain slightly elusive, it is clear that the different macrophages deal with each other, behind the scenes, to lobby for grafts to be accepted.
Spiller K.L., Anfang R.R., Spiller K.J., Ng J., Nakazawa K.R., Daulton J.W. & Vunjak-Novakovic G. (2014). The role of macrophage phenotype in vascularization of tissue engineering scaffolds, Biomaterials, DOI: 10.1016/j.biomaterials.2014.02.012
Mirza R.E., Fang M.M., Weinheimer-Haus E.M., Ennis W.J. & Koh T.J. (2014). Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice, Diabetes, 63 (3) 1103-1114. DOI: 10.2337/db13-0927
Amano S., Cohen J., Vangala P., Tencerova M., Nicoloro S., Yawe J., Shen Y., Czech M. & Aouadi M. (2014). Local Proliferation of Macrophages Contributes to Obesity-Associated Adipose Tissue Inflammation, Cell Metabolism, 19 (1) 162-171. DOI: 10.1016/j.cmet.2013.11.017
King R.L. & Weiss M.J. (2014). Iron-laden macrophage in autoimmune disease, Blood, 123 (4) 469-469. DOI: 10.1182/blood-2013-10-531954
Comito G., Giannoni E., Segura C.P., Barcellos-de-Souza P., Raspollini M.R., Baroni G., Lanciotti M., Serni S. & Chiarugi P. (2013). Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression, Oncogene, DOI: 10.1038/onc.2013.191
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