p75NTR suppression in rat bone marrow stromal stem cells significantly reduced their rate of apoptosis during neural differentiation

Edalat, Houri; Hajebrahimi, Zahra; Movahedin, Mansoureh; Tavallaei, Mahmood; Amiri, Sara; Mowla, Seyed Javad

doi:10.1016/j.neulet.2011.04.050

Cited by 14 publications

(15 citation statements)

References 25 publications

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“…BMSCs are also clinically attractive because they lend themselves to autologous transplantation in humans. Neural-like cells derived from BMSCs could be used in cell therapy for degenerative or traumatic diseases of the central nerve system [9-11]; thus, the efficacy of these cells as transplants has been investigated for the treatment of SCI [4,6,12,13]. …”

Section: Introductionmentioning

confidence: 99%

Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury

et al. 2013

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IntroductionRecently, cell-based therapy has gained significant attention for the treatment of central nervous system diseases. Although bone marrow stromal cells (BMSCs) are considered to have good engraftment potential, challenges due to in vitro culturing, such as a decline in their functional potency, have been reported. Here, we investigated the efficacy of rat BMSCs (rBMSCs) cultured under simulated microgravity conditions, for transplantation into a rat model of spinal cord injury (SCI).MethodsrBMSCs were cultured under two different conditions: standard gravity (1G) and simulated microgravity attained by using the 3D-clinostat. After 7 days of culture, the rBMSCs were analyzed morphologically, with RT-PCR and immunostaining, and were used for grafting. Adult rats were used for constructing SCI models by using a weight-dropping method and were grouped into three experimental groups for comparison. rBMSCs cultured under 1 g and simulated microgravity were transplanted intravenously immediately after SCI. We evaluated the hindlimb functional improvement for 3 weeks. Tissue repair after SCI was examined by calculating the cavity area ratio and immunohistochemistry.ResultsrBMSCs cultured under simulated microgravity expressed Oct-4 and CXCR4, in contrast to those cultured under 1 g conditions. Therefore, rBMSCs cultured under simulated microgravity were considered to be in an undifferentiated state and thus to possess high migration ability. After transplantation, grafted rBMSCs cultured under microgravity exhibited greater survival at the periphery of the lesion, and the motor functions of the rats that received these grafts improved significantly compared with the rats that received rBMSCs cultured in 1 g. In addition, rBMSCs cultured under microgravity were thought to have greater trophic effects on reestablishment and survival of host spinal neural tissues because cavity formations were reduced, and apoptosis-inhibiting factor expression was high at the periphery of the SCI lesion.ConclusionsHere we show that transplantation of rBMSCs cultured under simulated microgravity facilitates functional recovery from SCI rather than those cultured under 1 g conditions.

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Section: Introductionmentioning

confidence: 99%

Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury

et al. 2013

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“…P75, a neurotrophin receptor, has been proven to induce apoptosis of neurons [117]. P75-suppressed BMSC decreases the level of apoptosis during neural differentiation in vitro [118]. Furthermore, transplanting p75 siRNA transfected BMSC in SCI rats could promote functional recovery [119].…”

Section: Combination Of Rnai and Stem Cells For Treatment Of Cns Dmentioning

confidence: 99%

Combination of RNA Interference and Stem Cells for Treatment of Central Nervous System Diseases

Hou

Wang

et al. 2017

Genes

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RNA interference (RNAi), including microRNAs, is an important player in the mediation of differentiation and migration of stem cells via target genes. It is used as a potential strategy for gene therapy for central nervous system (CNS) diseases. Stem cells are considered vectors of RNAi due to their capacity to deliver RNAi to other cells. In this review, we discuss the recent advances in studies of RNAi pathways in controlling neuronal differentiation and migration of stem cells. We also highlight the utilization of a combination of RNAi and stem cells in treatment of CNS diseases.

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“…NT-3 belongs to the same family of neurotrophins as BDNF, and has been shown to play a protective role in the degeneration of adult central noradrenergic neurons in vivo [105,106]. CNTF has been reported to rescue the degenerating striatal neurons in primate and rodent models [45,107]. Furthermore, the absence of CNTF leads to the apoptosis of motor neurons in adult mice [46,108].…”

Section: Lineage Restricted Honps Retain Their Capability To Produce mentioning

confidence: 99%

“…Several studies have shown that neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3), etc. are important for the survival and function of dopaminergic neurons in CNS [43][44][45][46][47]. Recent studies also indicate that the neurotrophins have the potential to optimize the local micro-environment of the damaged area, and thereby induce endogenous stem cells to replace or rescue degenerating neurons [48,49].…”

Section: Introductionmentioning

confidence: 99%

Lineage restriction of adult human olfactory-derived progenitors to dopaminergic neurons

Wang¹,

Lu²,

Li³

et al. 2011

SCD

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Human adult olfactory epithelium contains neural progenitors (hONPs) which replace damaged cellular components throughout life. Methods to isolate and expand the hONPs which form neurospheres in vitro have been developed in our laboratory. In response to morphogens, the hONPs differentiate along several neural lineages. This study optimized conditions for the differentiation of hONPs towards dopaminergic neurons. The hONPs were treated with Sonic hedgehog (Shh), in the presence or absence of retinoic acid (RA) and/or forskolin (FN). Transcription factors (nurr1, pitx3 and lmx1a) that promote embryonic mouse or chicken dopaminergic development were employed to determine if they would modulate lineage restriction of these adult human progenitors. Four expression vectors (pIRES-pitx3-nurr1, pLN-CX2-pitx3, pLNCX2-nurr1 and pLNCX2-lmx1a) were transfected into the hONPs, respectively. Transcription factor expression and the rate-limiting enzyme in dopamine synthesis tyrosine hydroxylase (TH) were detected in the transfected cells after 4 month-selection with G418, indicating transfected hONPs were stably restricted towards a dopaminergic lineage. Furthermore, a dopamine enzyme immunoassay (EIA) was employed to detect the synthesis and release of dopamine. The most efficient transfection paradigm was determined. Several neurotrophic factors were detected in the pre-transfected hONPs which have potential roles in the maintenance, survival and proliferation of dopaminergic neurons. Therefore the effect of transfection on the neurotrophin synthesis was examined. Transfection did not alter synthesis. The use of olfactory progenitors as a cell-based therapy for Parkinson’s disease (PD) would allow harvest without invasive surgery, provide an autologous cell population, eliminate need for immunosuppression and avoid the ethical concerns associated with embryonic tissues. This study suggests that specific transcription factors and treatment with morphogens can restrict human adult olfactory-derived progenitors to a dopaminergic neuronal lineage. Future studies will evaluate the utility of these unique cells in cell-replacement paradigms for the treatment of PD like animal models

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p75NTR suppression in rat bone marrow stromal stem cells significantly reduced their rate of apoptosis during neural differentiation

Cited by 14 publications

References 25 publications

Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury

Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury

Combination of RNA Interference and Stem Cells for Treatment of Central Nervous System Diseases

Lineage restriction of adult human olfactory-derived progenitors to dopaminergic neurons

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