Chimerism of Murine Fetal Bone Marrow by Maternal Cells Occurs in Late Gestation and Persists into Adulthood

Abstract

SUMMARY:Studies of murine severe combined immune-deficient (scid/scid) fetuses gestating in transgene-tagged immune competent dams have established high frequencies of transplacental trafficking of nucleated maternal cells. Maternal cells first appeared in thymus at gestation day (gd) 12.5 and were present in more than 90% of late gestation fetuses. Morphologically heterogeneous maternal cells were located predominantly in bone marrow and thymus and also occasionally in liver, spleen, and nonlymphoid organs. We have now evaluated maternal cell chimerism in offspring with normal lymphoid development. Genetically normal blastocysts from random-bred CD1 mice were transferred to C57BL/6J-lacZ transgene-tagged ROSA26 females. Serial sectioning of fetuses followed by histochemistry for lacZ-expressing cells was used to comprehensively define organs containing maternal cells. Fetuses, sectioned in their entirety, had no detectable maternal cells before gd 16.5. Morphologically homogenous, nucleated maternal cells were first present in fetal bone marrow cavities at gd 16.5 and were evident in all offspring in later gestation. Postnatally, maternal cells were also present in bone marrow cavities into adulthood, as determined by lacZ histochemistry and PCR amplification of the maternal transgene. The frequency of maternally derived cells in postnatal bone marrow was increased compared with late gestation, and occasionally, maternal cells were detected in postnatal spleen. The normalcy of maternal cell transfer to genetically immune competent progeny and their long-term engraftment is suggestive of a functional role for maternal cells in offspring. (Lab Invest 2003, 83:673-681).

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

“…MMc has been reported in infants in the thymus, liver, thyroid, skin (18), and heart (16) and in the peripheral blood of healthy adults (8). In an experimental model, maternal cells were found in the bone marrow of immune-competent mice during gestation and increased postnatally (19). Thus, accumulating evidence indicates MMc persists in the circulation and tissues of a mother's children, raising important questions as to whether MMc confers benefits during development, has beneficial or adverse effects later in life, and about the meaning of tolerance within a chimeric self.…”

Trafficking of Multipotent Mesenchymal Stromal Cells from Maternal Circulation Through the Placenta Involves Vascular Endothelial Growth Factor Receptor-1 and Integrins

“…To explore the mechanism of maternal stem cell transmission to conceptuses in utero, we delivered cells intravenously at E17 and assessed fetal organs collected at E21, as well as 3-12 weeks after delivery. Marleau et al [7] reported maternal cells first appearing in fetal thymus at E12.5, coincident with the maturation of the hemochorial interface [1]. Morphologically heterogeneous maternal cells were present predominantly in bone marrow and thymus in more than 90% of late-gestation fetuses.…”

“…Maternal cells have been demonstrated in fetal circulation [5] and in liver, spleen, thymus, thyroid, and skin of neonatal organs [6]. Long-term engraftment of maternal cells in the postnatal bone marrow and spleen has been detected in a rodent model [7]. Humans, rats, and mice have hemochorial placentas [8], but the nature of the specific cell types and the regulatory mechanisms that orchestrate the trafficking of maternal cells through the placenta are not known.…”

A Role for DNA Polymerase μ in the Emerging DJH Rearrangements of the Postgastrulation Mouse Embryo

“…Considering that each exsanguinated embryo (and its dissected organs) was sequentially diluted in large buffer volumes (well over 10 6 times its own volume), the possibility of surgical contamination with B cells from the adult mice was low. Alternatively, DJ H joints could represent mother-derived chimerism, although only a transient wave of maternal macrophages has been detected in E7.5 to E9.5 embryo yolk sacs and no other cell chimerism in fetuses up to E16 (6,52). Additional support for the embryo origin of the N ϩ DJ H s came from their unbiased ORF usage, while ORF2 was absent among adult N ϩ DJ H s (P Ͻ 0.01 compared to embryo ORF2 usage) (Fig.…”