Transplanted CNS stem cells form functional synapses in vivo

Abstract

An understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro-expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies.

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

“…22 Other short-term studies have noted neuronal differentiation, synapse formation and electrophysiological connectivity after transplantation of neural precursor cells. 23 Beside these synaptic connections, secretion of neurotrophic factors, including transforming growth factor-a and brain-derived neurotrophic factor, from transplanted differentiated cells can contribute to functional recovery. 24 Transplantation of neural-induced MSCs alone or in combination with undifferentiated MSCs has a significantly better effect in comparison with transplantation of MSCs alone.…”

Neurorestorative treatment of stroke: Cell and pharmacological approaches

“…The cellular approach includes a variety of cells, including neural stem and progenitor cells, cord blood, and mesenchymal stem cells (MSCs). [13][14][15][16][17][18] The search for pharmacological therapies that potentiate the recovery process after a neurological injury has intensified during the last decade. Many therapeutic agents already marketed have been shown to promote functional outcome after stroke, 7,19 -22 including trophic and growth factors (e.g., vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), and BDNF), granulocyte colony-stimulating factor (G-CSF), angiopoietin 1 (ANG1), angiotensin modulators, minocycline, and thiazolidinediones.…”

Electrophysiological evaluation of engrafted stem cell-derived neurons

“…The third technology additionally serves as a useful tool for studying the maturation and integration of donor cells in controlled, real-time scenarios. Crucial for studying vital donor cells in recipient tissues is the availability of genetically labeled donor cells that are readily identifiable in situ by expression of fluorescent indicator proteins (e.g., enhanced green fluorescent protein (EGFP)), under the control of either cell-type specific or constitutively active promoters [25][26][27][28][29][30] .…”