Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially parous mdx females.
Throughout every pregnancy, genetically distinct fetal microchimeric stem/progenitor cells (FMCs) engraft in the mother, persist long after delivery, and may home to damaged maternal tissues. Phenotypically normal fetal lymphoid progenitors have been described to develop in immunodeficient mothers in a fetus-treats-its-mother paradigm. Since stem cells contribute to muscle repair, we assessed this paradigm in the mdx mouse model of Duchenne muscular dystrophy. mdx females were bred serially to either ROSAeGFP males or mdx males to obtain postpartum microchimeras that received either wild-type FMCs or dystrophin-deficient FMCs through serial gestations. To enhance regeneration, notexin was injected into the tibialis anterior of postpartum mice. FMCs were detected by qPCR at a higher frequency in injected compared to noninjected side muscle (P=0.02). However, the number of dystrophin-positive fibers was similar in mothers delivering wild-type compared to mdx pups. In addition, there was no correlation between FMC detection and percentage dystrophin, and no GFP+ve FMCs were identified that expressed dystrophin. In 10/11 animals, GFP+ve FMCs were detected by immunohistochemistry, of which 60% expressed CD45 with 96% outside the basal lamina defining myofiber contours. Finally we confirmed lack of FMC contribution to statellite cells in postpartum mdx females mated with Myf5-LacZ males. We conclude that the FMC contribution to regenerating muscles is insufficient to have a functional impact.
UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia. e.seppanen@uq.edu.au
Elke Jane
EJ
Seppanen
Samantha Susan
SS
Hodgson
Kiarash
K
Khosrotehrani
George
G
Bou-Gharios
Nicholas M
NM
Fisk
D000818:Animals; D016189:Dystrophin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D053686:Fetal Stem Cells / Q000276:immunology / Q000502:physiology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D012038:Regeneration
D016189:Dystrophin; D004546:Elapid Venoms; D049452:Green Fluorescent Proteins; C005082:notexin