Tumor xenograft

Tumor xenografts are transplants of human tumor cells into immunocompromised mice. A tumor develops within a few weeks, allowing the drug’s response to be studied directly in vivo. Several key advantages are associated with tumor xenografts. It accurately reflects a patient’s tumor since they are biologically stable. 

Specifically, they provide precision in studying histopathology, gene expression, and inflammation. This method is also used to evaluate the toxicity of therapeutics. In addition to being expensive, tumor xenografts are a bit complex to implement technically. As a result, every assay is extremely valuable. 

Tumour xenograft can be performed in several ways, such as: 

Patient-Derived Xenografts 

Patient-Derived Xenografts PDX is a xenograft developed directly from primary human tissue. The treatment plan for a consented cancer patient includes surgical resection. A xenograft is created from part of the resected tissue. Typically, a single cell suspension or small fragments of the original surgical specimen are dissected and implanted in immunodeficient mice. The second round of immunodeficient hosts is used to expand samples that grow successfully. Passaging refers to this process. For the PDX, passage numbers are restricted as close to the patient as possible to reduce the tumor’s adaptation to the mouse host. 

Advantages of Patient-Derived Xenografts 

As described in a review article, patient-derived xenografts are biologically stable when passaged in mice, including gene expression patterns, mutational status, metastatic potential, drug responsiveness, and tumor architecture. By retaining tumor heterogeneity, gene expression, and similar response to treatment, low passage PDX may reproduce the original patient’s tumor better. Therefore, PDXs are considered more translational as drug development tools.  

The clinical history of some PDX may be available. Patients whose tumors have previously been treated with a first-line therapeutic may be selected for the study of a new drug. The power of PDX mice lies in their ability to capture the genetic heterogeneity of a tumor from one patient and many patients’ tumors simultaneously. Using that combination, we can predict which drugs will benefit patients upfront.  

Drawbacks of Patient-Derived Xenografts 

It can be more difficult and expensive to set up PDX studies logistically. Engraving 100 nude mice with HeLa cells and screening them on Monday is relatively simple with cell line xenografts. PDX models can make this more difficult. PDX models are not available for all types of tumors. It can take a long time and be expensive to experiment with some PDX models because they grow slowly. PDX models are also difficult to access. 

The acceptance of patient-derived xenografts in mice and rats has been studied extensively. These models typically contain human immune systems or are severely immunodeficient to prevent rejection of foreign tissue. 

Ectopic Tumor Xenograft 

Mouse hind legs or backs are usually injected with human cancer cells subcutaneously. Ectopic tumor xenografts (ectopic models) have a transplanted site different from the cell’s origin. Oncology studies use the ectopic model to validate and assess cancer. Researchers have used ectopic models to evaluate anticancer efficacy because they can easily monitor tumorigenicity and tumor growth. 

Orthotopic Tumour Xenograft 

A variety of alternative models have been developed to assess tumor sensitivity. Xenografts derived from orthotopic tumors are advanced tools but use an immunosuppressive murine microenvironment. A human cancer cell transplant is performed orthotopically at the same location where the tumor originated. It is essential to ensure reproducibility in this model that a well-trained expert with surgical skills is involved.  

Because almost all tumors except melanoma are invisible to the naked eye, it isn’t easy to calculate the take rate of tumorigenicity. Contrary to subcutaneous ectopic models, orthotopic models only allow measurement of tumor growth without sacrifice. 

Metastatic Cancer Model 

Localized tumors formed by ultraviolet, ionizing radiation, and carcinogens invade vessels and lymph nodes and cause metastasis (secondary cancer) at susceptible sites. As per the seed and soil hypothesis of Paget, a primary cancer cell (seed) metastasizes to lungs, livers, bones, lymph nodes, and brains in a suitable environment. 

Studies of the mechanisms of metastasis have spurred the development of metastasis inhibitors and preventive drugs, but guidelines to approve clinical trials have not been established based on preclinical evaluations. 

EZ Derm Xenograft 

The collagen in EZ Derm is cross-linked with an aldehyde to create a porcine-derived xenograft. Skin injuries caused by partial thickness loss can be treated using EZ Derm (porcine xenograft). Using EZ Derm reduces pain and fluid loss associated with burns, donor sites, and chronic vascular ulcers. 

When a person is severely burned or injured and missing large areas of skin, EZ Derm xenografts can be used to restore the skin temporarily. As a temporary treatment, it protects exposed tissue from external contaminants and decreases protein loss and cell death while protecting the exposed tissue from external contaminants. 

Autografts are not always feasible treatment options depending on the size and location of the skin injury. A thin layer of skin can be taken from an unaffected area after the skin beneath the xenograft has healed to an acceptable state to cover the tissue injury. It might be necessary to use a meshed graft if there is not enough donor skin available. That involves stretching and slicing the donor skin to create a larger mesh-like covering1. In the clinic, both options have proven successful, although recovery from this graft is more difficult and takes longer.