the body’s own UFOs!

The body’s own “UFOs!” (unidentified foreign objects)

By: Mari Yamamoto and Hadeel Saab

No, we’re not talking about aliens on earth. We are talking about how your body detects alien materials and triggers your immune system to attack and surround them with a tough defense shield of dense scar tissue, preventing the foreign objects from doing anything. While this defense has been critical to our survival as a species, it also is a difficult hurdle in the development of medical device implants, including beta-cell implants to treat T1D.

The culprit molecule

This bodily defense process is known as fibrosis, and researchers at MIT and Boston Children’s Hospital have unmasked what’s going on:

  • They discovered colony-stimulating factor-1 (CSF-1), a signaling molecule integral to the development of mature macrophages that start the fibrosis process1
  • By testing implants made of different biomaterial, they were able to shut down CSF-1’s signaling to discover:
    • Fibrosis around the implants no longer occurred1
    • The macrophages continued with their other important responsibilities, like phagocytosis and wound healing1

But the big question is how can this discovery be effectively and safely applied to implants? We are happy to report that many have risen to the challenge of developing implants that get around this not-so-little issue:

  • Co-encapsulation of mesenchymal cells
    • Mesenchymal stem cells (MSC) were stimulated with proinflammatory cytokines to improve their anti-inflammatory properties2
    • When co-encapsulated or co-transplanted, the MSC were able to reduce pericapsular fibrotic overgrowth and allow for better allograft survival2
  • MIT researchers developed Crystalline drug formations
    • These formations are slowly released from the device itself, allowing for long-term use of the device and suppression of the foreign-body response3
  • Eimear Dolan, a biomedical engineer from Ireland, developed a dynamic soft reservoir (DSR)
    • This device is made of soft material that has the ability to oscillate and cause fluid flow so that the foreign-body response tissue can’t form4
  • Researchers from the University of Toronto have come out with a device-less biomaterial approach that the body is less likely to reject. In their method:
    • Before islet transplantation in the subcutaneous space, the space was pre-vascularized using methacrylic acid-based biomaterials that allowed the transplanted islets to stably achieve normoglycemia

What’s next? The problem of fibrosis has been an obstacle for many scientists working with medical device implants to treat T1D. But, thanks to a variety of innovative approaches, a non-alien implantable treatment looks promising in the near future.

Sources

  1. Doloff, J., Veiseh, O., Vegas, A., Tam, H., Farah, S., Ma, M., . . . Anderson, D. (2017, March 20). Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Retrieved June 27, 2020, from https://www.nature.com/articles/nmat4866
  2. Vaithilingam, V., Evans, M., Lewy, D. M., Bean, P. A., Bal, S., & Tuch, B. E. (2017). Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted. Scientific reports, 7(1), 10059. https://doi.org/10.1038/s41598-017-10359-1
  3. Farah, S., Doloff, J.C., Müller, P. et al. Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations. Nat. Mater. 18, 892–904 (2019). https://doi.org/10.1038/s41563-019-0377-5
  4. Dolan, E., Varela, C., Mendez, K., Whyte, W., Levey, R., Robinson, S., . . . Roche, E. (2019, August 28). An actuatable soft reservoir modulates host foreign body response. Retrieved June 27, 2020, from https://robotics.sciencemag.org/content/4/33/eaax7043
  5. Vlahos, A. E., Talior-Volodarsky, I., Kinney, S. M., & Sefton, M. V. (2020). A scalable device-less biomaterial approach for subcutaneous islet transplantation. bioRxiv

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