Mesenchymal Stem Cells Promote an Increase in Neuronal Oscillation via Glutamate Tonic Release.

Mesenchymal stromal cells (MSCs) hold therapeutic potential for neurological disorders, but their impact on neuronal activity remains unclear. We investigated the effects of SB623 cells (Notch-1 intracellular domain-transfected MSCs) and parental MSCs on human induced pluripotent stem cell (iPSC)-derived neurons using multi-electrode arrays. SB623 cells significantly increased neuronal activity and oscillation in a dose-dependent manner, surpassing astrocytes in promoting network bursts.

αSMA Expression in Large Colonies of Colony-Forming Units-Fibroblast as an Early Predictor of Bone Marrow MSC Expandability.

Clinical applications of mesenchymal stromal cells (MSCs) require the manufacture of large cell lots, which involves multiple passages for cell expansion and sometimes genetic modification. MSCs from various sources, including bone marrow (BM), exhibit high donor-to-donor variability in their growth characteristics. This can lead to unpredictable manufacturing outcomes with respect to success or failure of individual lots.

Cell Injury-Induced Release of Fibroblast Growth Factor 2: Relevance to Intracerebral Mesenchymal Stromal Cell Transplantations.

Beneficial effects of intracerebral transplantation of mesenchymal stromal cells (MSC) and their derivatives are believed to be mediated mostly by factors produced by engrafted cells. However, the mesenchymal cell engraftment rate is low, and the majority of grafted cells disappear within a short post-transplantation period. Here, we hypothesize that dying transplanted cells can affect surrounding tissues by releasing their active intracellular components.

Comparison of the neuropoietic activity of gene-modified versus parental mesenchymal stromal cells and the identification of soluble and extracellular matrix-related neuropoietic mediators.

Introduction: Transplanting mesenchymal stromal cells (MSCs) or their derivatives into a neurodegenerative environment is believed to be beneficial because of the trophic support, migratory guidance, immunosuppression, and neurogenic stimuli they provide. SB623, a cell therapy for the treatment of chronic stroke, currently in a clinical trial, is derived from bone marrow MSCs by using transient transfection with a vector encoding the human Notch1 intracellular domain. This creates a new phenotype, which is effective in experimental stroke, exhibits immunosuppressive and angiogenic activity equal or superior to parental MSCs in vitro, and produces extracellular matrix (ECM) that is exceptionally supportive for neural cell growth.

Proteomic analysis of the extracellular matrix produced by mesenchymal stromal cells: implications for cell therapy mechanism.

Mesenchymal stromal cells (MSCs) transiently transfected with notch1 intracellular domain (NICD) are beneficial for neurological disorders as observed in several preclinical studies. Extracellular matrix (ECM) derived from NICD-transfected MSCs has been previously shown to support in vitro neural cell growth and survival better than that of un-transfected MSCs. To understand the underlying mechanism(s) by which NICD-transfected MSC-derived ECM supports neural cell growth and survival, we investigated the differences in NICD-transfected MSC- and MSC-derived ECM protein quantity and composition.

Quantitative microplate assay for studying mesenchymal stromal cell-induced neuropoiesis.

Transplanting mesenchymal stromal cells (MSCs) or their derivatives in a neurodegenerative environment is believed to be beneficial because of the trophic support, migratory guidance, and neurogenic stimuli they provide. There is a growing need for in vitro models of mesenchymal-neural cell interactions to enable identification of mediators of the MSC activity and quantitative assessment of neuropoietic potency of MSC preparations. Here, we characterize a microplate-format coculture system in which primary embryonic rat cortex cells are directly cocultured with human MSCs on cell-derived extracellular matrix (ECM) in the absence of exogenous growth factors.

Comparing the immunosuppressive potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells.

Background: SB623 cells are expanded from marrow stromal cells (MSCs) transfected with a Notch intracellular domain (NICD)-expressing plasmid. In stroke-induced animals, these cells reduce infarct size and promote functional recovery. SB623 cells resemble the parental MSCs with respect to morphology and cell surface markers despite having been in extended culture.

Extracellular matrix produced by bone marrow stromal cells and by their derivative, SB623 cells, supports neural cell growth.

Several studies have shown the benefits of transplanting bone marrow-derived multipotent mesenchymal stromal cells (MSC) into neurodegenerative lesions of the central nervous system, despite a low engraftment rate and the poor persistence of grafts. It is known that the extracellular matrix (ECM) modulates neuritogenesis and glial growth, but little is known about effects of MSC-derived ECM on neural cells. In this study, we demonstrate in vitro that the ECM produced by MSC can support neural cell attachment and growth.