Bone Marrow Mononuclear Cells Increase Retinal Ganglion Cell Survival and Axon Regeneration in the Adult Rat

Zaverucha-do-Valle, Camila; Gubert, Fernanda; Bargas-Rega, Michelle; Coronel, Juliana; Mesentier-Louro, Louise A.; Mencalha, André Luiz; Abdelhay, Eliana; Santiago, Marcelo F.; Mendez-Otero, Rosália

doi:10.3727/096368910x524764

Cited by 56 publications

(61 citation statements)

References 56 publications

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“…This explanation can be supported by our previous observation that BMC treatment enhances glial cell proliferation and neuronal survival [5]. Interestingly, increased levels of FGF-2 with bone marrow cells therapy have also been reported in regenerating tissue in a model of optic nerve crush lesions [15]. …”

Section: Discussionsupporting

confidence: 56%

“…Several mechanisms have been suggested to explain how BMMC contribute to improve cell therapy following nerve injury [1,5,15,19,20]. Initial observations suggested that bone marrow multipotent stem cells could differentiate into any neural cell type depending on the environment conditions [21-24].…”

Section: Discussionmentioning

confidence: 99%

“…It was also recently demonstrated an increase in the expression of FGF-2 in axons of retinal ganglion cells treated with bone marrow mononuclear cells in a model of optic nerve crush [15] and this increase was correlated with a larger number of regenerating axons [15]. In other tissues such as heart it has been shown that soluble factors derived from bone marrow derived mesenchymal cells rescue cardiomiocytes from necrosis in vitro and were able to promote recovery of basic parameters of cardiac function in vivo [16].…”

Section: Introductionmentioning

confidence: 99%

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Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

Ribeiro-Resende

Carrier-Ruiz

Lemes

et al. 2012

Molecular Neurodegeneration

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BackgroundAmong the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2) is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS).ResultsHere we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL) region of the lumbar spinal cord (LSC) in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM) resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly.ConclusionWe conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

Ribeiro-Resende

Carrier-Ruiz

Lemes

et al. 2012

Molecular Neurodegeneration

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“…Cell‐based therapy has been intensively studied. Different types of cells from diverse sources have been investigated for neuro‐repair after ON injury, including Schwann cells, fibroblasts, olfactory ensheathing cells, and bone marrow mononuclear cells . These cells can serve as biological mini‐pumps, releasing trophic factors to promote RGC survival and axonal regeneration.…”

Section: Discussionmentioning

confidence: 99%

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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“…Following an optic nerve crush, many axotomized retinal ganglion cells die due to a lack of target-derived neurotrophic factors. But the delivery of bone-marrow mononuclear cells provides neuroprotection and increases both retinal ganglion cell survival and axon outgrowth 106. Similarly, mesenchymal stem cells transplanted into the rat brain reduce ischemia- induced brain damage in rats by inducing a marked increase in the synthesis of neurotrophic factors such as vascular endothelial growth factor, epidermal growth factor, and basic fibroblast growth factor in the host brain 107.…”

Section: Neuroprotectionmentioning

confidence: 99%

Maximizing neuroprotection: where do we stand?

Kuffler¹

2012

TCRM

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Brain and spinal cord traumas include blunt and penetrating trauma, disease, and required surgery. Such traumas trigger events such as inflammation, infiltration of inflammatory and other cells, oxidative stress, acidification, excitotoxicity, ischemia, and the loss of calcium homeostasis, all of which cause neurotoxicity and neuron death. To prevent trauma-induced neurological deficits and death, each of the many neurotoxic events that occur in parallel or sequentially must be minimized or prevented. Although neuroprotective techniques have been developed that block single neurotoxic events, most provide only limited neuroprotection and are only applied singly. However, because many neurotoxicity triggers arise from common events, an approach for invoking more effective neuroprotection is to apply multiple neuroprotective methods simultaneously before the many neurotoxic triggers and cascades are initiated and become irreversible. This paper first discusses some triggers of neurotoxicity and neuroprotective mechanisms that block them, including hypothermia, alkalinization, and the administration of adenosine. It then examines how the simultaneous application of these techniques provides significantly greater neuroprotection than is provided by any technique alone. The paper also stresses the importance of determining whether the neuroprotection provided by these techniques can be further enhanced by combining them with additional techniques, such as the systemic administration of glucocorticoids. Finally, the paper stresses the absolute critical importance of applying these techniques within the “golden hour” following trauma, before the many neurotoxic events and cascades are manifest and before the neurotoxic cascades become irreversible.

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Bone Marrow Mononuclear Cells Increase Retinal Ganglion Cell Survival and Axon Regeneration in the Adult Rat

Cited by 56 publications

References 56 publications

Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

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

Maximizing neuroprotection: where do we stand?

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