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Mouse Regenerating Myofibers Detected as False-Positive Donor Myofibers with Anti-Human Spectrin

Rozkalne, A; Adkin, C; Meng, J; Lapan, A; Morgan, JE; Gussoni, E; (2014) Mouse Regenerating Myofibers Detected as False-Positive Donor Myofibers with Anti-Human Spectrin. Human Gene Therapy , 25 (1) 73 - 81. 10.1089/hum.2013.126. Green open access

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Abstract

Stem cell transplantation is being tested as a potential therapy for a number of diseases. Stem cells isolated directly from tissue specimens or generated via reprogramming of differentiated cells require rigorous testing for both safety and efficacy in preclinical models. The availability of mice with immune-deficient background that carry additional mutations in specific genes facilitates testing the efficacy of cell transplantation in disease models. The muscular dystrophies are a heterogeneous group of disorders, of which Duchenne muscular dystrophy is the most severe and common type. Cell-based therapy for muscular dystrophy has been under investigation for several decades, with a wide selection of cell types being studied, including tissue-specific stem cells and reprogrammed stem cells. Several immune-deficient mouse models of muscular dystrophy have been generated, in which human cells obtained from various sources are injected to assess their preclinical potential. After transplantation, the presence of engrafted human cells is detected via immunofluorescence staining, using antibodies that recognize human, but not mouse, proteins. Here we show that one antibody specific to human spectrin, which is commonly used to evaluate the efficacy of transplanted human cells in mouse muscle, detects myofibers in muscles of NOD/Rag1nullmdx5cv, NOD/LtSz-scid IL2Rγnull mice, or mdx nude mice, irrespective of whether they were injected with human cells. These “reactive” clusters are regenerating myofibers, which are normally present in dystrophic tissue and the spectrin antibody is likely recognizing utrophin, which contains spectrin-like repeats. Therefore, caution should be used in interpreting data based on detection of single human-specific proteins, and evaluation of human stem cell engraftment should be performed using multiple human-specific labeling strategies.

Type: Article
Title: Mouse Regenerating Myofibers Detected as False-Positive Donor Myofibers with Anti-Human Spectrin
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/hum.2013.126
Publisher version: http://dx.doi.org/10.1089/hum.2013.126
Language: English
Additional information: © Mary Ann Liebert, Inc. This work is licensed under a Creative Commons Attribution 3.0 United States License. You are free to copy, distribute, transmit and adapt this work, but you must attribute this work as ‘‘Human Gene Therapy. Copyright 2013 Mary Ann Liebert, Inc. http://liebertpub.com/hum, used under a Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/us/’’
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1435405
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