In healthy couples over half of the conceptions result in failed pregnancy and around 30% of them occur during implantation defining it as a rate-limiting step for the success of native and in vitro fertilization. The understanding of the factors regulating each step of implantation and immune recognition is critical for the pregnancy outcome. Creation of 3D-cell culture models, such as spheroids and organoids, is in the focus of placental tissue engineering in attempt to resemble the in vivo complexity of the maternal-fetal interface and to overcome the need of laboratory animals and human embryos. We constructed stable, reliable, and reproducible trophoblast Sw71 spheroids which are functional independently of the serum level in the culture media. These models resemble the hatched human blastocyst in size, shape and function and are useful for in vitro studies of the in vivo concealed human implantation. Since Sw71 spheroids produce HLA-C, the only classical MHC molecule indispensable for establishment of the immune tolerance and proper human implantation, they are applicable for the evaluation not only of implantation itself but also of maternal-trophoblasts immune interactions. In addition, Sw71-blastocyst-like spheroids are manipulable in low-volume platform, easy to monitor and analyze automatically under treatment with favorable/detrimental factors.
Two major types of natural killer cell receptors (NKR) recognize main histocompatibility complex (MHC) class I molecules: the evolutionarily conserved and non-polymorphic, heterodimeric killer C-type lectin-like receptors (KLRs) (CD94/NKG2) and polygenic and highly polymorphic killer immunoglobulin-like receptors (KIRs). Whereas CD94/NKG2 bind to non-classical MHC class Ib molecules, KIRs bind to classical MHC class Ia molecules HLA-A, HLA-B, and HLA-C. MHC in humans is called human leukocyte antigen (HLA) system.This review highlights some features of the KIR/HLA (allo)recognition by decidual NK (dNK) cells as a major immune cell population specifically enriched at maternal-fetal interface (MFI) during human early pregnancy. In addition, KIR/HLA (allo)recognition axis
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