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

Abstract

ABSTRACT؊ multipotent mesenchymal stromal cells are transferred to rat maternal venous blood, they traffic through the placenta, engraft in various fetal organs, and persist in offspring for at least 12 weeks. Cell proliferation ability is retained in the xenogeneic placenta. Maternofetal trafficking is significantly reduced by blocking antibodies against integrins ␣ 2 , ␣ 4 , ␣ 5 , and ␤ 1 or VEGFR-1. These results suggest that maternal microchimerism arises by the trafficking of multipotent mesenchymal stromal cells via VEGF-A-and integrin-dependent pathways across the hemochorial placenta to fetal tissues. STEM CELLS 2008;26: 550 -561 Disclosure of potential conflicts of interest is found at the end of this article.

In Vivo Implanted Bone Marrow-Derived Mesenchymal Stem Cells Trigger a Cascade of Cellular Events Leading to the Formation of an Ectopic Bone Regenerative Niche

“…Alternatively activated (M2) macrophages possess the capacity to facilitate tissue repair and regeneration [30]. Consistent with the MSC-mediated anti-inflammatory capacities already described by different authors [19] and with previous studies conducted using different experimental approaches [27,31], we showed that implanted MSCs caused an increased percentage of alternatively activated (CD206 pos CD51 pos ) M2 macrophages infiltrating the ectopic implants, and a decrease in the percentage of infiltrating proinflammatory (CD86 pos CD40 pos ) M1 macrophages. The secretory pattern of MSCs is highly influenced by their microenvironment, and, in particular, they are very sensitive to inflammatory stimuli [2,16,17].…”

“…Cells belonging to the innate immunity and, in particular, MC/Mph lead the inflammatory cascade reaction guiding revascularization and repair/regeneration of tissue at injury sites [12,13,27]. They exert this function by secreting inductive cytokines responsible for progenitor cell migration, a critical step in tissues that heal by regenerative processes rather than by a mere repair [28].…”

Why are levels of maternal microchimerism higher in type 1 diabetes pancreas?

“…2 Most studies of maternal microchimerism have focused on analysis of hematopoietic cells but it is increasingly clear from human 3 and animal studies 4 that microchimeric cells also exist in other tissues including the liver, heart and brain.…”

Chimeric maternal cells in offspring do not respond to renal injury, inflammatory or repair signals

“…Rhabdomyolysis was induced in 43 mice by intramuscular injection of glycerol, as previously described in reference 17. This model allowed for the investigation of MMc in kidneys harvested at distinct stages of acute injury (days 1-3), inflammation (days 4-7) and regeneration (days [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Control mice were either left untreated or given intramuscular injections of saline.…”