scholarly journals Subacute Transplantation of Native and Genetically Engineered Neural Progenitors Seeded on Microsphere Scaffolds Promote Repair and Functional Recovery After Traumatic Brain Injury

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141983018 ◽  
Author(s):  
Nolan B. Skop ◽  
Sweta Singh ◽  
Henri Antikainen ◽  
Chaitali Saqcena ◽  
Frances Calderon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Functional Recovery ◽  
Subventricular Zone ◽  
Brain Injuries ◽  
Radial Glia ◽  
Therapeutic Potential ◽  
Ventricular Zone ◽  
Neural Progenitors ◽  
Functional Improvement

There is intense interest and effort toward regenerating the brain after severe injury. Stem cell transplantation after insult to the central nervous system has been regarded as the most promising approach for repair; however, engrafting cells alone might not be sufficient for effective regeneration. In this study, we have compared neural progenitors (NPs) from the fetal ventricular zone (VZ), the postnatal subventricular zone, and an immortalized radial glia (RG) cell line engineered to conditionally secrete the trophic factor insulin-like growth factor 1 (IGF-1). Upon differentiation in vitro, the VZ cells were able to generate a greater number of neurons than subventricular zone cells. Furthermore, differentiated VZ cells generated pyramidal neurons . In vitro, doxycycline-driven secretion of IGF-1 strongly promoted neuronal differentiation of cells with hippocampal, interneuron and cortical specificity. Accordingly, VZ and engineered RG-IGF-1-hemagglutinin (HA) cells were selected for subsequent in vivo experiments. To increase cell survival, we delivered the NPs attached to a multifunctional chitosan-based scaffold. The microspheres containing adherent NPs were injected subacutely into the lesion cavity of adult rat brains that had sustained controlled cortical impact injury. At 2 weeks posttransplantation, the exogenously introduced cells showed a reduction in stem cell or progenitor markers and acquired mature neuronal and glial markers. In beam walking tests assessing sensorimotor recovery, transplanted RG cells secreting IGF-1 contributed significantly to functional improvement while native VZ or RG cells did not promote significant recovery. Altogether, these results support the therapeutic potential of chitosan-based multifunctional microsphere scaffolds seeded with genetically modified NPs expressing IGF-1 to promote repair and functional recovery after traumatic brain injuries.

In vitro differentiation of retinal ganglion-like cells from embryonic stem cell derived neural progenitors

2009 ◽  
Vol 380 (2) ◽  
pp. 230-235 ◽  
Author(s):  
Balusamy Jagatha ◽  
Mundackal S. Divya ◽  
Rajendran Sanalkumar ◽  
Chandrasekharan L. Indulekha ◽  
Sasidharan Vidyanand ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Neural Progenitors ◽  
Retinal Ganglion ◽  
In Vitro Differentiation

P315In-vivo and vitro mitochondrial transfer from adipose-derived mesenchymal stem cell to ischemic cardiomyocyte

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Mori ◽  
S Miyagawa ◽  
T Kawamura ◽  
H Hata ◽  
T Ueno ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Functional Recovery ◽  
Pcr Analysis ◽  
Sham Operation ◽  
Rat Cardiomyocytes ◽  
Mitochondrial Transfer ◽  
Group A

Abstract Background Although transplantation of human Adipose-derived Mesenchymal stem cell (hADSC) shows efficacy in the treatment of ischemic cardiomyopathy, its therapeutic mechanisms have not been fully elucidated. It has been already reported that mitochondria transfer to recipient cells have impact on resistance to injury and tissue regeneration, however this phenomenon has not been elucidated in the damaged heart. Therefore, we hypothesized that ADSC transfer own mitochondria to cardiomyocytes in-vivo and in-vitro under ischemic condition, resulting in the functional recovery of cardiomyocyte. Method and result Transplantation of hADSC (group A) to the heart surface or sham operation (group C) was performed in rats that were subjected to LAD ligation 2 weeks prior to the treatment (n=10 each). The number of transplant cell was 1x106/body. Three days after transplantation, transferred hADSCs' mitochondria were observed in recipient cardiomyocytes histologically (Figure). Quantitative PCR analysis revealed that mitochondrial genome of recipient myocytes increased over time. The cardiac function assessed with echocardiography was significantly better in group A. Furthermore, live-imaging of hADSC transplantation revealed the suspected transfer of mitochondria to beating heart. In-vitro, the co-culture of rat cardiomyocytes (rCM) and hADSC was observed with time-lapse photography and demonstrated mitochondrial transfer under the hypoxic condition. The measuring the oxygen consumption rate (OCR) of these cells showed that OCR of rCM was reinforced by co-culture with hADSC conspicuously. Figure 1 Conclusion Mitochondrial transfer from hADSC to rCM was suggested in-vivo and in-vitro ischemic condition and suspected to be related to functional recovery of ischemic cardiomyocyte.

scholarly journals Epsins Regulate Mouse Embryonic Stem Cell Exit from Pluripotency and Neural Commitment by Controlling Notch Activation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Marina Cardano ◽  
Jacopo Zasso ◽  
Luca Ruggiero ◽  
Giuseppina Di Giacomo ◽  
Matteo Marcatili ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Notch Signaling ◽  
Neural Differentiation ◽  
Radial Glia ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Progenitors ◽  
Notch Activation

Epsins are part of the internalization machinery pivotal to control clathrin-mediated endocytosis. Here, we report that epsin family members are expressed in mouse embryonic stem cells (mESCs) and that epsin1/2 knockdown alters both mESC exits from pluripotency and their differentiation. Furthermore, we show that epsin1/2 knockdown compromises the correct polarization and division of mESC-derived neural progenitors and their conversion into expandable radial glia-like neural stem cells. Finally, we provide evidence that Notch signaling is impaired following epsin1/2 knockdown and that experimental restoration of Notch signaling rescues the epsin-mediated phenotypes. We conclude that epsins contribute to control mESC exit from pluripotency and allow their neural differentiation by appropriate modulation of Notch signaling.

The Subventricular Zone: A Key Player in Human Neocortical Development

2017 ◽  
Vol 24 (2) ◽  
pp. 156-170 ◽  
Author(s):  
J. Alberto Ortega ◽  
Fani Memi ◽  
Nevena Radonjic ◽  
Radmila Filipovic ◽  
Inseyah Bagasrawala ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Subventricular Zone ◽  
Ventricular Zone ◽  
Cell Types ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Intrauterine Development ◽  
Vitro Model ◽  
Primate Cerebral Cortex

One of the main characteristics of the developing brain is that all neurons and the majority of macroglia originate first in the ventricular zone (VZ), next to the lumen of the cerebral ventricles, and later on in a secondary germinal area above the VZ, the subventricular zone (SVZ). The SVZ is a transient compartment mitotically active in humans for several gestational months. It serves as a major source of cortical projection neurons as well as an additional source of glial cells and potentially some interneuron subpopulations. The SVZ is subdivided into the smaller inner (iSVZ) and the expanded outer SVZ (oSVZ). The enlargement of the SVZ and, in particular, the emergence of the oSVZ are evolutionary adaptations that were critical to the expansion and unique cellular composition of the primate cerebral cortex. In this review, we discuss the cell types and organization of the human SVZ during the first half of the 40 weeks of gestation that comprise intrauterine development. We focus on this period as it is when the bulk of neurogenesis in the human cerebral cortex takes place. We consider how the survival and fate of SVZ cells depend on environmental influences, by analyzing the results from in vitro experiments with human cortical progenitor cells. This in vitro model is a powerful tool to better understand human neocortex formation and the etiology of neurodevelopmental disorders, which in turn will facilitate the design of targeted preventive and/or therapeutic strategies.

scholarly journals Mimicking Neural Stem Cell Niche by Biocompatible Substrates

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Citlalli Regalado-Santiago ◽  
Enrique Juárez-Aguilar ◽  
Juan David Olivares-Hernández ◽  
Elisa Tamariz
Keyword(s):  
Subventricular Zone ◽  
Current Knowledge ◽  
Ventricular Zone ◽  
Neurogenic Niche ◽  
Extracellular Matrix Components ◽  
The Central Nervous System ◽  
Cell Niche ◽  
Extracellular Environment

Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to buildingin vitromodels that include the relevant components of thein vivoniche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for thein vitroandin vivomimicking of extracellular NSCs conditions.

scholarly journals Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+hMSCs

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Schade ◽  
Paula Müller ◽  
Evgenya Delyagina ◽  
Natalia Voronina ◽  
Anna Skorska ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Nucleic Acid Delivery ◽  
Innovative Strategies ◽  
Genetic Modifications ◽  
Microrna Delivery ◽  
Magnetic Vectors

Genetic modifications of bone marrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to improve their therapeutic potential and enable innovative strategies in tissue regeneration. However, most of the studies use cultured hMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR carrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated hMSCs. MNP based transfection is preferable for genetic modificationsin vivodue to improved selectivity, safety of delivery, and reduced side effects. Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were testedin vitrofor uptake efficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes were selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag). We found that all tested transfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become crucial for virus-free introduction of therapeutic miRs as well as other nucleic acidsin vivo. Moreover, in the field of targeted stem cell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulationin vitro.

Neural Progenitor Cells Derived from the Adult Rat Subventricular Zone: Characterization and Transplantation

2007 ◽  
Vol 16 (8) ◽  
pp. 799-810 ◽  
Author(s):  
Kevin Chen ◽  
Stephanie M. Hughes ◽  
Bronwen Connor
Keyword(s):  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Therapeutic Potential ◽  
Neural Progenitor ◽  
Adult Rat ◽  
Cell Purification ◽  
Adult Rat Brain ◽  
Percoll Density Gradient

In order to fully characterize and determine the therapeutic potential of adult neural progenitor cells (NPCs), it is important to be able to isolate and study NPCs from animals such as rats, in which there are existing models of brain injury and disease. The focus of this study was to characterize the cultivation, differentiation, and transplantation of adult rat NPCs isolated from the subventricular zone of the lateral ventricles. We examined strategies for cell purification using a Percoll density gradient, and cell expansion using a range of maintenance medium and plating densities. Purification by Percoll gradient enriched a population of cells expressing nestin and SOX2, but resulted in a significant reduction in neurosphere generation. Culturing adult rat NPCs in Neurobasal-A media and plating at 200,000 cell/ml resulted in a higher percentage of cells surviving to generate neurospheres compared to culture in DMEM/F12 or NS-A media. On induction of differentiation, adult rat NPCs were capable of generating neurons, astrocytes, and oligodendrocytes in vitro that survived for up to 8 weeks, demonstrating multipotentiality of these cells. In addition, a population of cells continued to proliferate during the initial phase of differentiation, suggesting the presence of two populations of NPCs during differentiation. Cultured adult rat NPCs also survived and differentiated into astrocytes 6 weeks after transplantation into the striatum of the normal adult rat brain. In conclusion, we have optimized techniques that allow for the routine isolation, culture, and transplantation of multipotent NPCs derived from the adult rat SVZ.

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