Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after @entity35 XXXX .

@entity35 @entity19372 @entity71 @entity10865 @entity5019 @entity10862 @entity1566
@entity71 following @entity1566 ( @entity1566 ) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after @entity1566 ( @entity1566 ). @entity35 bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress @entity10865 , receptor of @entity10862 ( @entity10862 ), were pre-differentiated into cells carrying neuronal features via co-culture with @entity10862 overproducing Schwann cells in 3-dimensional @entity19372 ( @entity19372 ) scaffold for 14 days in  vitro. Intra- @entity19372 formation of MSC assemblies emulating neural network (MSC- @entity19372 ) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC- @entity19372 or @entity19372 was then grafted acutely into a 2  mm-wide transection gap in the T9-T10 spinal cord segments of adult @entity35 . Eight weeks later, hindlimb function of the MSC- @entity19372 -treated @entity1566 @entity35 was significantly improved relative to controls receiving the @entity19372 or lesion only as indicated by BBB score. The MSC- @entity19372 transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in  vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered @entity5019 expression in the grafted and lumbar spinal cord cells of the treated @entity35 only. Our data suggest that MSC-derived neuron-like cells resulting from @entity10862 - @entity10865 -induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits.
