Abstract
The usage of stem cells is a promising strategy for the repair of damaged tissue in the injured brain. Recently, amniotic fluid (AF) cells have received a lot of attention as an alternative source of stem cells for cell-based therapies. However, the success of this approach relies significantly on proper interactions between graft and host tissue. In particular, the reestablishment of functional brain networks requires formation of gap junctions, as a key step to provide sufficient intercellular communication. In this study, we show that AF cells express high levels of CX43 (GJA1) and are able to establish functional gap junctions with cortical cultures. Furthermore, we report an induction of Cx43 expression in astrocytes following injury to the mouse motor cortex and demonstrate for the first time CX43 expression at the interface between implanted AF cells and host brain cells. These findings suggest that CX43-mediated intercellular communication between AF cells and cortical astrocytes may contribute to the reconstruction of damaged tissue by mediating modulatory, homeostatic, and protective factors in the injured brain and hence warrants further investigation.
Highlights
Recent advances in regenerative medicine have boosted efforts to explore the therapeutic potentials of stem cells to repair damaged tissue in the injured brain
Our results show that amniotic fluid (AF) cells ubiquitously expressed Connexin 43 (CX43) (GJA1) and CX45 (GJA7) at the gestation periods examined (AF15–AF35) (Figure 1(A))
We found an intracellular pool of CX43 in the perinuclear Golgi apparatus, as confirmed by trans-Golgi network membrane protein golgin-97-positive staining in AF cells (Figure 1(C), (a)-(b))
Summary
Recent advances in regenerative medicine have boosted efforts to explore the therapeutic potentials of stem cells to repair damaged tissue in the injured brain (reviewed in [1,2,3,4]). The transplantation of embryonic stem cells [5], fetal neural stem or progenitor cells [6,7,8], or bonemarrow-derived stem cells [9, 10] into the injured brain has been explored extensively. Human embryonic stem (ES) cells and fetal neural stem cells are subject to ethical considerations and the risk of tumor development, whereas adult neural stem cells have limited proliferation capabilities and lineage restriction. AF cells have been shown to harbour the potential for neurogenic differentiation, using different induction protocols [14, 18, 22,23,24,25]; the proof that these cells can differentiate into functional neurons remains elusive [26, 27]
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