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Background: Mesenchymal stem cells (MSC) of various origins are the most widely investigated type of stem cells in clinical trials. We report a treatment comparison of two adult sources of autologous MSCs regarding safety and efficacy in established spinal cord injury (SCI). Materials and Methods: In this Phase I/II open-label two-arm study, patients were divided into two groups. The first group was treated with autologous bone marrow-derived MSCs (BM-MSC), while the second was treated with autologous adipose tissue-derived MSCs (AT-MSC). Safety and outcomes were assessed in both groups for 24 months post-treatment initiation using the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Results: Both groups showed no serious treatment-emergent adverse events (TEAEs). AIS-assessed outcomes pointed to sensory and motor improvements in patients of both groups. Patients who received AT-MSCs showed better sensory and motor function improvement than those who received BM-MSCs. One patient in the AT-MSCs group regained the ability to walk after years of disability. Conclusions: Intrathecal injection of autologous AT-MSCs and autologous BM-MSC appears to be safe, with a possible advantage in the AT-MSCs treatment option regarding efficacy over BM-MSCs. Future clinical trials investigating larger sample sizes are warranted for wider use of this treatment modality in clinical practice. Furthermore, earlier use of cellular therapy intervention for SCI patients is predicted to improve the benefits. [ABSTRACT FROM AUTHOR]

Background. Neurodegenerative diseases are characterized by progressive neuronal loss and degeneration. The regeneration of neurons is minimal and neurogenesis is limited only to specific parts of the brain. Several clinical trials have been conducted using Mesenchymal Stem Cells (MSCs) from different sources to establish their safety and efficacy for the treatment of several neurological disorders such as Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Aim. The aim of this study was to provide a comparative view of the capabilities of MSCs, isolated from different human tissue sources to differentiate into neuronal stem cell-like cells (NSCs) and possibly into dopaminergic neural-like cells. Methods. Mesenchymal stem cells were isolated from human bone marrow, adipose, and Wharton's jelly (WJ) tissue samples. Cells were characterized by flow cytometry for their ability to express the most common MSC markers. The differentiation potential was also assessed by differentiating them into osteogenic and adipogenic cell lineages. To evaluate the capacity of these cells to differentiate towards the neural stem cell-like lineage, cells were cultured in media containing small molecules. Cells were utilized for gene expression and immunofluorescence analysis at different time points. Results. Our results indicate that we have successfully isolated MSCs from bone marrow, adipose tissue, and Wharton's jelly. WJ-MSCs showed a slightly higher proliferation rate after 72 hours compared to BM and AT derived MSCs. Gene expression of early neural stem cell markers revealed that WJ-MSCs had higher expression of Nestin and PAX6 compared to BM and AT-MSCs, in addition to LMX expression as an early dopaminergic neural marker. Immunofluorescence analysis also revealed that these cells successfully expressed SOX1, SOX2, Nestin, TUJ1, FOXA2 and TH. Conclusion. These results indicate that the protocol utilized has successfully differenti-ated BM, AT and WJ-MSCs into NSC-like cells. WJ-MSCs possess a higher potential to transdifferentiate into NSC and dopaminergic-like cells. Thus, it might indicate that this protocol can be used to induceMSCinto neuronal lineage, which provides an additional or alternative source of cells to be used in the neurological cell-based therapies. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) use their stemness properties to perpetuate their lineage and survive chemotherapy. Currently cell-based and cell-free therapies are under investigation to develop novel anti-cancer treatment modalities. We designed this study to investigate how cell extracts of mesenchymal stem cells affect the growth of glioma stem cells in vitro . Gliospheres were generated from the U87MG cell line and treated with conditioned media of Wharton's jelly and bone marrow mesenchymal stem cells. The effects were investigated at the functional and molecular levels. Our results showed that conditioned media from both types of mesenchymal stem cells changed the morphology of spheres and inhibited the proliferation, invasion, and self-renewal ability of glioma stem cells. At the molecular level, metabolism interruption at oxidative phosphorylation, cell cycle arrest, cell differentiation, and upregulation of the immune response were observed. Furthermore, this effect was mediated by the upregulation of the DKK1 gene inhibiting the Wnt pathway mediated by growth factor activity and downregulation of the KITLG gene activated by growth factor and cytokine activity, inhibiting multiple pathways. We conclude that different types of mesenchymal stem cells possess antitumor properties and their paracrine factors, in combination with anti-immune modalities, can provide practical therapeutic targets for glioblastoma treatment., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)