Infiltrating cells from host brain restore the microglial population in grafted cortical tissue

Abstract

Transplantation of embryonic cortical tissue is considered as a promising therapy for brain injury. Grafted neurons can reestablish neuronal network and improve cortical function of the host brain. Microglia is a key player in regulating neuronal survival and plasticity, but its activation and dynamics in grafted cortical tissue remain unknown. Using two-photon intravital imaging and parabiotic model, here we investigated the proliferation and source of microglia in the donor region by transplanting embryonic cortical tissue into adult cortex. Live imaging showed that the endogenous microglia of the grafted tissue were rapidly lost after transplantation. Instead, host-derived microglia infiltrated and colonized the graft. Parabiotic model suggested that the main source of infiltrating cells is the parenchyma of the host brain. Colonized microglia proliferated and experienced an extensive morphological transition and eventually differentiated into resting ramified morphology. Collectively, these results demonstrated that donor tissue has little contribution to the activated microglia and host brain controls the microglial population in the graft.

Characterization of Inflammation in Delayed Cortical Transplantation

“…Care was taken to maintain the original dorso-ventral and anteroposterior orientations of the cortical fragments during the transplantation procedure. We did not perform immunosuppression during transplantation since it has been demonstrated in several previous studies including ours (Gaillard et al, 2007, 2009; Thompson et al, 2009; Klein et al, 2013; Wang et al, 2016; Péron et al, 2017), that immunosuppression is not necessary for grafted fetal mouse cells to survive in a mouse brain as performed in the present study. No animal was excluded after histological analysis.…”

Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?

“…In studies on the possible therapeutic effect of fetal embryonic cortical tissue transplanted into the host brain parenchyma, it was reported that the microglial cells residing in the fetal tissue vanished quickly, and host-derived microglia cells inhabited transplanted neural tissue without any harm to it. Thus, the microglia cells play an essential role in CNS homeostasis-not only as immunocompetent cells, but also as regulators of the neural network after fetal development and rearrangement while learning their function in late ontogeny [ 25 ].…”

Three-dimensional analysis revealed that microglia have different structural features in different brain regions of mice

“…为明显 [24,25] Microglia are immune cells of the central nervous system, and can constantly monitor the changes in surrounding environment by extending or retracting their ramified processes. To investigate the differences in morphological features of microglia in different brain regions, brain slices of transgenic mice expressing green fluorescent protein (GFP) were prepared and the structure of microglia in the cortex, striatum and polymorph layer of the dentate gyrus (PoDG) were imaged and quantified by combining techniques of tissue clearing, laser scanning confocal microscopy and three-dimensional reconstruction.…”