What is a Xenograft?

At the time of injury, autografts are not always feasible treatment options depending on the size and location of the skin injury. Once the skin underneath the xenograft has healed to an acceptable state, a thin layer of skin may be taken from an unaffected location and used to cover the tissue injury. However, if not enough donor skin is available a meshed graft will need to be used, wherein the donor skin is stretched and sliced to create a larger mesh-like covering¹. Recovery from this graft is more difficult and takes longer, but both options have proved successful in the clinic².

Patient-Derived Xenografts (PDX) for Oncology Research

A second use for xenografts is in oncology research. In order to develop a personalized treatment plan for cancer patients, a small segment of their tumor may be excised and subsequently grafted into an immunodeficient or humanized mouse. These are referred to as patient-derived xenografts (PDX)³.

In addition to personalized treatments, PDX models allow for the study of the tumor and its natural growth patterns and behavior. Depending on the tumor's original location it can be transplanted under the skin or into the organ that the tumor was originally derived from.

Humanized Mice

The advent of humanized mice has introduced even more options to the mouse model landscape — allowing researchers to engraft tumors to a mouse that contains a human immune system. Multiple models with these modifications are based on the NOG background and have been engrafted with human hematopoietic stem cells.

After stable engraftment of human hematopoietic stem cells, human lymphocytes will be present in peripheral blood, bone marrow, the thymus, and the spleen. These models present unique and invaluable platforms for studying novel immunotherapies on patient-derived tumors.

References:

1. Skin grafting. Accessed May 13, 2019.
2. Fatah, M. F.; Ward, C. M. The Morbidity of Split-Skin Graft Donor Sites in the Elderly: The Case for Mesh-Grafting the Donor Site. Br. J. Plast. Surg. 1984, 37 (2), 184-190.
3. Lai, Y.; Wei, X.; Lin, S.; Qin, L.; Cheng, L.; Li, P. Current Status and Perspectives of Patient-Derived Xenograft Models in Cancer Research. J. Hematol. Oncol. 2017, 10 (1), 1-14.
4. Blunt, T.; Finnie, N. J.; Taccioli, G. E.; Smith, G. C.; Demengeot, J.; Gottlieb, T. M.; Mizuta, R.; Varghese, A. J.; Alt, F. W.; Jeggo, P. A.; et al. Defective DNA-Dependent Protein Kinase Activity Is Linked to V(D)J Recombination and DNA Repair Defects Associated with the Murine Scid Mutation. Cell 1995, 80 (5), 813-823.
5. Richmond, A.; Su, Y. Mouse Xenograft Models vs GEM Models for Human Cancer Therapeutics. Dis. Model. Mech. 2008, 1 (2-3), 78-82.
6. Shinkai, Y.; Rathbun, G.; Lam, K. P.; Oltz, E. M.; Stewart, V.; Mendelsohn, M.; Charron, J.; Datta, M.; Young, F.; Stall, A. M. RAG-2-Deficient Mice Lack Mature Lymphocytes Owing to Inability to Initiate V(D)J Rearrangement. Cell 1992, 68 (5), 855-867.
7. Ito, M.; Hiramatsu, H.; Kobayashi, K.; Suzue, K.; Kawahata, M.; Hioki, K.; Ueyama, Y.; Koyanagi, Y.; Sugamura, K.; Tsuji, K.; et al. NOD/SCID/ Ɣ_c^null Mouse: An Excellent Recipient Mouse Model for Engraftment of Human Cells. Blood 2002, 100 (9), 3175-3182.