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Updated: Jan 18, 2026
Performing Human Skeletal Muscle Xenografts in Immunodeficient Mice
Published on: September 16, 2019
Performing Human Skeletal Muscle Xenografts in Immunodeficient Mice
Kyla A Britson1, Aaron D Black2, Kathryn R Wagner3
1Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine; Department of Neurology, Johns Hopkins University School of Medicine.
Abstract:
Treatment effects observed in animal studies often fail to be recapitulated in clinical trials. While this problem is multifaceted, one reason for this failure is the use of inadequate laboratory models. It is challenging to model complex human diseases in traditional laboratory organisms, but this issue can be circumvented through the study of human xenografts. The surgical method we describe here allows for the creation of human skeletal muscle xenografts, which can be used to model muscle disease and to carry out preclinical therapeutic testing. Under an Institutional Review Board (IRB)-approved protocol, skeletal muscle specimens are acquired from patients and then transplanted into NOD-Rag1null IL2rγnull (NRG) host mice. These mice are ideal hosts for transplantation studies due to their inability to make mature lymphocytes and are thus unable to develop cell-mediated and humoral adaptive immune responses. Host mice are anaesthetized with isoflurane, and the mouse tibialis anterior and extensor digitorum longus muscles are removed. A piece of human muscle is then placed in the empty tibial compartment and sutured to the proximal and distal tendons of the peroneus longus muscle. The xenografted muscle is spontaneously vascularized and innervated by the mouse host, resulting in robustly regenerated human muscle that can serve as a model for preclinical studies.
Insights
Researchers developed a surgical method to create human skeletal muscle xenografts in mice. This novel model enables better preclinical therapeutic testing for complex human muscle diseases.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Translational Science
Background:
- Animal models often fail to predict human treatment responses in clinical trials.
- Developing accurate models for complex human diseases like muscle disorders remains a significant challenge.
- Human xenografts offer a promising alternative to traditional animal models for disease study.
Purpose of the Study:
- To describe a surgical technique for creating human skeletal muscle xenografts.
- To establish a preclinical model for studying muscle diseases.
- To facilitate therapeutic testing for muscle conditions.
Main Methods:
- Human skeletal muscle specimens were obtained under Institutional Review Board (IRB) approval.
- Specimens were transplanted into immunodeficient NOD-Rag1null IL2rγnull (NRG) mice.
- Surgical implantation involved placing human muscle into the mouse tibialis anterior compartment and suturing.
Main Results:
- The xenografted human muscle demonstrated spontaneous vascularization and innervation by the mouse host.
- Robust regeneration of human skeletal muscle was achieved within the mouse model.
- The xenografts successfully served as a platform for preclinical studies.
Conclusions:
- The described surgical method effectively generates human skeletal muscle xenografts.
- This model provides a viable platform for preclinical testing of therapies for muscle diseases.
- Human xenografts represent a significant advancement in modeling human diseases for research.
