BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro. Issue 11 (30th June 2019)

• Record Type: Journal Article
• Authors: Scheper, Verena; Schwieger, Jana; Hamm, Anika; Lenarz, Thomas; Hoffmann, Andrea
• Other Names: Thippeswamy Thimmasettappa guestEditor.
• Is Part Of: Journal of neuroscience research. Volume 97:Issue 11(2019)
• Page Start: 1414
• Page End: 1429
• Publication Date: 2019-06-30
• Subjects: cell‐based therapy -- chronic therapy -- drug delivery -- endogenous pharmacotherapy -- neuroprotection -- spiral ganglion neuron; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24488
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic factors a sustained application, e.g., via cell‐based delivery is necessary. Human mesenchymal stem cells (hMSCs) were lentivirally modified to overexpress brain‐derived neurotrophic factor (BDNF) and to express fluorescent marker genes for easy visualization. Since genetically modified cells should be site‐specifically retained (e.g., by encapsulation) in the patients to avoid adverse effects the cells were additionally differentiated to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. Different polycations for lentiviral transduction were investigated for their efficiency. The success of differentiation was determined by analysis of chondrocyte marker genes and the neuroprotective effect of BDNF‐overexpressing cells was exemplarily investigated on neurons of the peripheral auditory system. The genetically modified hMSCs overexpressed BDNF from under 1 to 125 ng ml −1 day −1 depending on the donor and transfection method. Using protamine sulfate the transfection efficacy was superior compared to the use of polybrene. The BDNF secreted by the MSCs was significantly neuroprotective in comparison to the relevant controls even though the produced mean concentrations were lower than the effective concentrations for recombinant industrially produced proteins described in literature. The presented system of BDNF‐overexpressing hMSCs is neuroprotective and is therefore considered as a promising method for sustained delivery of proteins in therapeutically relevant amounts to degenerating neuronal structures. Abstract : Cell‐based drug delivery is a promising approach for future neuroprotective therapies. We infected human mesenchymal stem cells to overexpress BDNF and differentiated them to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. The BDNF‐overexpressing hMSCs protect neurons significantly better from degeneration than native MSCs. This finding has a high potential for future clinical application of hMSCs in human neuronal disorders therapy.