Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially parous mdx females

Seppanen, Elke Jane, Hodgson, Samantha Susan, Khosrotehrani, Kiarash, Bou-Gharios, George and Fisk, Nicholas M. (2012) Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially parous mdx females. Stem Cells and Development, 21 15: 2809-2816. doi:10.1089/scd.2012.0047


Author Seppanen, Elke Jane
Hodgson, Samantha Susan
Khosrotehrani, Kiarash
Bou-Gharios, George
Fisk, Nicholas M.
Title Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially parous mdx females
Journal name Stem Cells and Development   Check publisher's open access policy
ISSN 1547-3287
1557-8534
Publication date 2012-10-01
Year available 2012
Sub-type Article (original research)
DOI 10.1089/scd.2012.0047
Open Access Status Not yet assessed
Volume 21
Issue 15
Start page 2809
End page 2816
Total pages 8
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Language eng
Abstract 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.
Formatted abstract
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.
Keyword Cell & Tissue Engineering
Hematology
Medicine, Research & Experimental
Transplantation
Cell Biology
Hematology
Research & Experimental Medicine
Transplantation
CELL & TISSUE ENGINEERING
HEMATOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
TRANSPLANTATION
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 569822
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
 
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