Human Mesenchymal Stem Cells Produce Bioactive Neurotrophic Factors: Source, Individual Variability and Differentiation Issues

Paradisi, Mario Paglialunga; Alviano, Francesco; Pirondi, Stefania; Lanzoni, Giacomo; Fernández, Mercedes; Lizzo, Giulia; Giardino, Luciana; Giuliani, Alessandro; Costa, Roberta; Marchionni, Cosetta; Bonsi, Laura; Calzà, Laura

doi:10.1177/039463201402700309

Cited by 32 publications

(23 citation statements)

References 39 publications

(40 reference statements)

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“…In our study, we found that the BDNF , CNTF , GDNF , and NTF3 genes were highly expressed in human PDLSCs, but not the IGF1 , NGF , VEGFA , FGF1 , FGF2 , TGFA , OCM , and LIF genes (Fig. A), indicating different spectra of neurotrophic factors secretion by human PDLSCs compared to MSCs from different tissue origins . Notably, we discovered a novel neuroprotective mechanism of human adult stem cells that retina coculture enhances BDNF secretion from human PDLSCs by more than twofold (Fig.…”

Section: Discussionmentioning

confidence: 70%

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury

Cen

Liang

et al. 2018

Stem Cells

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Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury. Human PDLSCs were intravitreally injected into the vitreous chamber of adult Fischer rats after ONC in vivo as well as cocultured with retinal explants in vitro. Human PDLSCs survived in the vitreous chamber and were maintained on the RGC layer even at 3 weeks after ONC. Immunofluorescence analysis of βIII-tubulin and Gap43 showed that the numbers of surviving RGCs and regenerating axons were significantly increased in the rats with human PDLSC transplantation. In vitro coculture experiments confirmed that PDLSCs enhanced RGC survival and neurite regeneration in retinal explants without inducing inflammatory responses. Direct cell-cell interaction and elevated brain-derived neurotrophic factor secretion, but not promoting endogenous progenitor cell regeneration, were the RGC protective mechanisms of human PDLSCs. In summary, our results revealed the neuroprotective role of human PDLSCs by strongly promoting RGC survival and axonal regeneration both in vivo and in vitro, indicating a therapeutic potential for RGC protection against optic neuropathies. Stem Cells 2018;36:844-855.

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Section: Discussionmentioning

confidence: 70%

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury

Cen

Liang

et al. 2018

Stem Cells

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“…There is currently no therapy that sufficiently improves clinical recovery after ischemic stroke (Sims & Muyderman, ; Stankowski & Gupta, ). Adult neural stem cell (NSC) replacement therapy is a promising treatment for neurological recovery both structurally and functionally: It includes endogenous NSC regeneration to replace damaged tissue or neural cells in adulthood and exogenous adult NSC transplant after injuries such as ischemic stroke (Arvidsson, Collin, Kirik, Kokaia, & Lindvall, ; Chung et al, ; Koch, Kokaia, Lindvall, & Brustle, ; Paradisi et al, ). Adult NSCs are clinically important not only because ischemic stroke occurs mainly in adults but also because they are easy to obtain, with no medical ethics problems and no tumorigenicity (Giusto, Donega, Cossetti, & Pluchino, ).…”

Section: Introductionmentioning

confidence: 99%

mfat‐1 transgene protects cultured adult neural stem cells against cobalt chloride‐mediated hypoxic injury by activating Nrf2/ARE pathways

Yang

Fang

et al. 2017

J of Neuroscience Research

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Ischemic stroke is a devastating neurological disorder and one of the leading causes of death and serious disability in adults. Adult neural stem cell (NSC) replacement therapy is a promising treatment for both structural and functional neurological recovery. However, for the treatment to work, adult NSCs must be protected against hypoxic-ischemic damage in the ischemic penumbra. In the present study, we aimed to investigate the neuroprotective effects of the mfat-1 transgene on cobalt chloride (CoCl 2 )-induced hypoxic-ischemic injury in cultured adult NSCs as well as its underlying mechanisms. The results show that in the CoCl 2 -induced hypoxic-ischemic injury model, the mfat-1 transgene enhanced the viability of adult NSCs and suppressed CoCl 2 -mediated apoptosis of adult NSCs. Additionally, the mfat-1 transgene promoted the proliferation of NSCs as shown by increased bromodeoxyuridine labeling of adult NSCs. This process was related to the reduction of reactive oxygen species. Quantitative real-time polymerase chain reaction and Western blot analysis revealed a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genes (HO-1, NQO-1, GCLC). Taken together, our findings show that the mfat-1 transgene restored the CoCl 2 -inhibited viability and proliferation of NSCs by activating nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signal pathway to inhibit oxidative stress injury.

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“…Stem cell based therapy is a new approach in neurodegenerative diseases on central nervous system (CNS) which is potent to solve major pathophysiologies due to the stem cells ability in reducing the inflammation, reconstructioning of blood brain barrier and making some neural regenerations by secreting some neurotrophic factors including basic fibroblast growth factor (bFGF), endothelial growth factor (EGF), brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), etc. ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats

Hosseini

Farahmandnia

Razi

et al. 2015

IJSC

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ObjectivesBrain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke.Method and MaterialsThe Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups.ResultThe group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups.ConclusionsThe combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

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Human Mesenchymal Stem Cells Produce Bioactive Neurotrophic Factors: Source, Individual Variability and Differentiation Issues

Abstract: The first two authors contributed equally to this study This paper is dedicated to the memory of Gian Paolo Bagnara, master in mesenchymal stem cells, science, life.

Cited by 32 publications

References 39 publications

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury

Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury

mfat‐1 transgene protects cultured adult neural stem cells against cobalt chloride‐mediated hypoxic injury by activating Nrf2/ARE pathways

Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats

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