Microchimeric fetal cells cluster at sites of tissue injury in lung decades after pregnancy

O’Donoghue, Keelin; Sultan, Hanan; Al-Allaf, Faisal A.; Anderson, Jonathan; Wyatt-Ashmead, Josephine; Fisk, Nicholas M.

doi:10.1016/s1472-6483(10)60600-1

Cited by 82 publications

(78 citation statements)

References 33 publications

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“…Accordingly, fetal cell migration has been reported in other malignancies. 16,21,22 In breast carcinomas associated with pregnancies, 90% of specimens showed fetal cells in malignant tissue but never in benign mammary lesions developing also during pregnancy. 16 Fetal cell detection appears lower in our skin chemical murine model, but mice were not pregnant at the time of tumour development.…”

Section: Discussionmentioning

confidence: 99%

Early phase of maternal skin carcinogenesis recruits long‐term engrafted fetal cells

Huu

Khosrotehrani

Oster

et al. 2008

Intl Journal of Cancer

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During pregnancy, fetal cells enter the maternal circulation. These may be mesenchymal stem cells, haematopoietic or endothelial progenitors, which may persist for decades and be recruited to damaged maternal tissues. Recently, fetal cells were also identified in tumour tissues such as cervical cancer and breast carcinomas. However, the timing of malignant tumour infiltration was not demonstrated. In this study, we used two step carcinogenesis to assess the presence of fetal cells in early phases of skin tumour formation in previously pregnant mice. Wild-type female C57/BL6 mice were bred to transgenic mice for EGFP. After delivery, skin papillomas were induced by two-step carcinogenesis. The tumours were dissected 9 months after gestation. Fetal cells were identified in 75% of cutaneous papillomas (9/12 tumours), but never in normal skin from the same mice. Fetal cells expressed von-Willebrand factor, and less frequently CD45 or cytokeratin but did not express the tumoral epidermal keratins. Our study shows that long-term engrafted fetal cells home to early stage skin tumours where they participate in formation of the stroma. ' 2008 Wiley-Liss, Inc.Key words: two step carcinogenesis; pregnancy; fetal cells; microchimerism In a relatively frequent number of situations, a low number of donor cells are found in the peripheral blood or the tissues of a genetically different recipient. This phenomenon, called microchimerism, results mainly from pregnancy. Indeed, during gestation, fetal cells cross the placenta, enter the maternal circulation and persist after delivery in 20-50% of women.1 Solid organ transplantation, red blood cell transfusion or exchange between twins also lead to a similar microchimerism. The fetal cells transferred to the mothers include hematopoietic progenitors in humans 3,4 and mouse models 5 as well as mesenchymal stem cells.6 Several studies have shown that fetal cells are able to migrate to damaged maternal tissues such as thyroid, liver, intestine or cervix in humans 7,8 and liver, kidney, skin or brain in mouse models. [9][10][11][12] In these tissues, fetal cells may adopt the phenotype of the affected organ. 13 The participation of microchimeric cells in tumours developing in the recipient has been a subject of interest in the past years. Indeed, Kaposi sarcomas developing after kidney transplantation have been shown to derive mainly from donor cells.14 We have recently described the participation of donor derived cells in malignant skin tumours developing after organ transplantation. 15 In one case, the tumour was composed of donor derived keratinocytes suggesting that progenitor cells of donor origin had engrafted in the recipient skin and underwent transformation upon exposure to carcinogenic stimuli. However, in most cases of this study, skin tumours contained chimeric cells but did not originate from these. Besides, the participation of fetal cells in maternal tumour stroma has also been suggested in breast cancer during gestation. 16 However, to date, only few studies have consi...

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Section: Discussionmentioning

confidence: 99%

Early phase of maternal skin carcinogenesis recruits long‐term engrafted fetal cells

Huu

Khosrotehrani

Oster

et al. 2008

Intl Journal of Cancer

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“…The method adopted for FISH was initially described by Johnson et al 42,43 As reported by O'Donoghue et al, 44 skin sections (5 µm) were processed in the usual way, then heat and enzyme pre-treated and fixed before hybridization. This technique was tested on normal skin, scarred and hypertrophic tissue, where the duration of heat enzyme pre-treatment was adjusted.…”

Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

“…Slides were rinsed in tap water and dehydrated in 100% ethanol for 30 s. After being air-dried, the slides were mounted in DAPI (diamidino-2-phenyl-indole, Vector Laboratories), covered with 22 × 22mm coverslips, and sealed with nail varnish. 16,19,[42][43][44] Fluorescent Immunohistochemistry combined with FISH In order to identify the phenotype of microchimeric cells found in the tissue sections, Immunohistochemistry for markers of fetal wound healing was performed with Cytokeratin, Collagen I, III, Fibronectin, Transforming growth factor β1 (TGFβ1), and Transforming growth factor β3 (TGFβ3), was done on the same sections following FISH. (Table 6).…”

Section: Fluorescent Immunohistochemistrymentioning

confidence: 99%

“…Slides were finally dehydrated in 100% ethanol for 1 min and mounted in DAPI/ H1000 (Vector Laboratories) for analysis by epifluorescence microscopy. 16,19,[42][43][44] Imaging and analysis Following FISH, Immunohistochemistry with fluorescent Streptavidin method and Combined ImmunoFISH, slides were analyzed by epifluorescence microscopy (Zeiss Axioskope), using single band pass filters for Green, Red, and DAPI and the triple band filter set. Images were then captured using a cooled CCD camera and reviewed in Carl Zeiss Axiovision Rel.…”

Section: Fluorescent Immunohistochemistrymentioning

confidence: 99%

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Microchimeric fetal cells play a role in maternal wound healing after pregnancy

Mahmood

O’Donoghue

2014

Chimerism

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Fetal cells persist in mothers for decades after delivery: in a phenomenon called fetal microchimerism. While persistent fetal cells were first implicated in autoimmune disease, parallel studies in animal and human pregnancy now suggest that microchimeric fetal cells play a role in the response to tissue injury. The aim of this study was to investigate the impact of fetal microchimeric cells in the adult wound, using caesarean section (Cs) as a model of wound healing in pregnancy. XY-FIsh (fluorescence in situ hybridization) and immunostaining was used in multiple tissue sections from Cs skin biopsies from 70 women, to locate, quantitate and characterize microchimeric male presumed-fetal cells. Y-FIsh and Nested PCR was used to confirm XY-FIsh results. XY-FIsh demonstrated the presence of isolated 0-9 male fetal cells per section in the epidermis of the healed Cs scars from only those women who had their first male child by Cs. Both Y-FIsh and Y-PCR confirmed the presence of fetal cells in Cs scars. Combined FIsh and immunostaining showed all male fetal cells present were keratinocytes, as they expressed cytokeratin, and were almost exclusively located in epidermis. Microchimeric fetal cells also expressed Collagen I, III, and TGF-β3 in healed maternal scars. Identification of male-presumed fetal cells in healed maternal Cs scars after pregnancy suggests that, possibly in response to signals produced by maternal skin injury at Cs, fetal cells migrate to the site of damage to become involved in maternal tissue repair, or proliferate locally.

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“…FMCs selectively home to damaged tissues where they are found in a higher frequency than in uninjured control tissues [6,7]. They can either be a part of the inflammatory infiltrate or integrated into the surrounding maternal tissue, displaying niche-appropriate phenotypes [4,8].…”

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confidence: 99%

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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Microchimeric fetal cells cluster at sites of tissue injury in lung decades after pregnancy

Cited by 82 publications

References 33 publications

Early phase of maternal skin carcinogenesis recruits long‐term engrafted fetal cells

Early phase of maternal skin carcinogenesis recruits long‐term engrafted fetal cells

Microchimeric fetal cells play a role in maternal wound healing after pregnancy

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

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