Natural history of fetal cell microchimerism during and following murine pregnancy

Khosrotehrani, Kiarash; Johnson, Kirby L.; Guégan, Sarah; Stroh, Helene; Bianchi, Diana W.

doi:10.1016/j.jri.2005.02.001

Cited by 113 publications

(108 citation statements)

References 24 publications

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“…Our laboratory has reported on the use of transgenic male mice mated to wildtype female mice for studies of fetal cell microchimerism, in which the transgene represents a unique, paternally inherited sequence that can be used to identify fetal cells in maternal tissues (5,6). Once expressed, the protein product of the transgene can also be used as a marker of fetal cells.…”

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confidence: 99%

Quantification of green fluorescent protein by in vivo imaging, PCR, and flow cytometry: Comparison of transgenic strains and relevance for fetal cell microchimerism

et al. 2008

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Animal models are increasingly being used for the assessment of fetal cell microchimerism in maternal tissue. We wished to determine the optimal transgenic mouse strain and analytic technique to facilitate the detection of rare transgenic microchimeric fetal cells amongst a large number of maternal wild-type cells. We evaluated two strains of mice transgenic for the enhanced green fluorescent protein (EGFP): a commercially available, commonly used strain (C57BL/6-Tg(ACTB-EGFP)10sb/J) (CAG) and a newly created strain (ROSA26-EGFP) using three different techniques: in vivo and ex vivo fluorescent imaging (for whole body and dissected organs, respectively), PCR amplification of gfp, and flow cytometry (FCM). By fluorescent imaging, organs from CAG mice were 10-fold brighter than organs from ROSA26-EGFP mice (P < 0.0001). By PCR, more transgene from CAG mice was detected compared to ROSA26-EGFP mice (P 5 0.04). By FCM, ROSA26-EGFP cell fluorescence was more uniform than CAG cells. A greater proportion of cells from ROSA26-EGFP organs were positive for EGFP than cells from CAG organs, but CAG mice had a greater proportion of cells with the brightest fluorescent intensity. Each transgenic strain possesses characteristics that make it useful under specific experimental circumstances. The CAG mouse model is preferable when experiments require brighter cells, whereas ROSA26-EGFP is more appropriate when uniform or ubiquitous expression is more important than brightness. Investigators must carefully select the transgenic strain most suited to the experimental design to obtain the most consistent and reproducible data. In vivo imaging allows for phenotypic evaluation of whole animals and intact organs; however, we did not evaluate its utility for the detection of rare, fetal microchimeric cells in the maternal organs. Finally, while PCR amplification of a paternally inherited transgene does allow for the quantitative determination of rare microchimeric cells, FCM allows for both quantitative and qualitative evaluations of fetal cells at very high sensitivity in a plethora of maternal organs. '

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Quantification of green fluorescent protein by in vivo imaging, PCR, and flow cytometry: Comparison of transgenic strains and relevance for fetal cell microchimerism

et al. 2008

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“…An alternative, and more likely, explanation for the limited impact we observed could be the relative infrequency of persistent FMCs among maternal cells [29]. Despite maximizing the dose of FMCs acquired by mothers through serial breeding [29], their proportion was small (0.001%) compared to maternal cells.…”

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confidence: 85%

“…It is thought that these constant cycles of muscle degeneration-regeneration eventually lead to premature satellite cell exhaustion and consequent demise in this animal [37]. Since a local notexin insult is known to recruit bone marrow populations to aid in this repair process [38], we postulated that persistent FMCs (likely from the bone marrow compartment [8,29]) would be similarly recruited and participate in this repair process. Our results however cannot exclude the possibility that FMCs below detectable levels reside locally, proliferate, and become detectable in response to injury.…”

Section: Discussionmentioning

confidence: 99%

“…Despite maximizing the dose of FMCs acquired by mothers through serial breeding [29], their proportion was small (0.001%) compared to maternal cells. Moreover, the dystrophin mutation in mdx is X-linked [43], limiting potential benefits to FMCs acquired from female fetuses, and thus 50% of the progeny (regardless of their GFP expression).…”

Section: Discussionmentioning

confidence: 99%

“…To examine whether FMCs are recruited specifically to notexin-damaged muscles, we amplified the paternally inherited GFP transgene [29]. GFP gDNA was detected in all postpartum mdx females that had produced GFP transgenic fetuses.…”

Section: Fmcs Are Specifically Recruited To Muscles After Notexin Injurymentioning

confidence: 99%

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Fetal Microchimeric Cells in a Fetus-Treats-Its-Mother Paradigm Do Not Contribute to Dystrophin Production in Serially ParousmdxFemales

Seppanen

Hodgson²,

Khosrotehrani³

et al. 2012

Stem Cells and Development

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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.

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Fetal Cell Microchimerism, a Low‐Grade Naturally Occurring Celltherapy

Leduc

Aractingi

Khosrotehrani

2009

Perinatal Stem Cells

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Natural history of fetal cell microchimerism during and following murine pregnancy

Cited by 113 publications

References 24 publications

Quantification of green fluorescent protein by in vivo imaging, PCR, and flow cytometry: Comparison of transgenic strains and relevance for fetal cell microchimerism

Quantification of green fluorescent protein by in vivo imaging, PCR, and flow cytometry: Comparison of transgenic strains and relevance for fetal cell microchimerism

Fetal Microchimeric Cells in a Fetus-Treats-Its-Mother Paradigm Do Not Contribute to Dystrophin Production in Serially ParousmdxFemales

Fetal Cell Microchimerism, a Low‐Grade Naturally Occurring Celltherapy

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