Human Amniotic Fluid Cells Form Functional Gap Junctions with Cortical Cells

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.

Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine

“…However, we are also investigating the possibility that AF cells could be used for direct cellular delivery of certain types of molecules via gap junctional communication, as has been suggested by Brink et al [ 152 ] for bone marrow mesenchymal stromal cells. AF cells express connexins, the proteins that make up gap junction hemichannels, and are capable of establishing gap junctional communication with cultured cortical cells, as evidenced by dye transfer [ 112 ]. Given the induction of connexin expression surrounding a surgical lesion to motor cortex, [ 112 ] as well as in other models of brain injury [ 153 – 155 ], it is hoped that AF cells might be capable of delivering small molecules through gap junctions to host cells, in an effort to protect the surrounding tissue or promote repair mechanisms.…”

Gap Junctions in Developing Thalamic and Neocortical Neuronal Networks

“…Electrical synapses can change signal integration properties of neurons that possess sublinear dendritic integration mechanisms (cerebellar Golgi cells); gap junctions, by spreading the excitatory synaptic charge into the dendrites of other cells, counteract the effects of sublinear dendritic integration, enabling inputs to be more effective ( Vervaeke et al 2012 ). Apart from the fundamental importance of understanding electrical communication in the mammalian brain, therapeutical implications of gap junctions have also started to surface ( Jezierski et al 2012 ); amniotic fluid cells express high levels of Cx43 and are able to establish functional gap junctions with cortical neurons following injury, which may help with the reconstruction of damaged nervous tissue. Future studies can bring even more insight into this increasingly interesting field of vertebrate gap junctions.…”

Applications of the amniotic membrane in tissue engineering and regeneration: the hundred-year challenge

“…The AFCs on the other hand were used as an effective cell-based therapy for acute or chronic renal failures and acute tubular necrosis in animal models [ 74 ]. The AFCs were reported to facilitate neuroprotection during intercellular coupling due to their high expression levels of gap junction protein [ 75 ]. Moreover, the AFCs were found to support intercellular communication with astrocytes, highlighting their role in delivering therapeutic factors, such as microRNAs, to damaged tissues [ 75 ].…”