Stem cell therapy for nerve injury

Sayad-Fathi, Sara; Zaminy, Arash

doi:10.4252/wjsc.v9.i9.144

Cited by 48 publications

(22 citation statements)

References 112 publications

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“…Despite meticulous surgical techniques and non-surgical treatments, fully functional recovery is rarely achieved. Therefore, there is a demand for new approaches to stimulate effective peripheral nerve regeneration after injury [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine

et al. 2020

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Neurotrophic factors play a key role in the development, differentiation, and survival of neurons and nerve regeneration. In the present study, we evaluated the effect of certain neurotrophic factors (NGF, BDNF, and GDNF) on axon growth and migration of Nestin-green fluorescent protein (GFP)-positive cells using a 3D model of dorsal root ganglion (DRG) explant culture in Matrigel. Our method generally represents a convenient model for assessing the effects of soluble factors and therapeutic agents on axon growth and nerve regeneration in R&D studies. By analyzing the DRG explants in ex vivo culture for 21 days, one can evaluate the parameters of neurite outgrowth and the rate of cell migration from the DRG explants into the Matrigel. For the current study, we used Nestin-GFP-expressing mice in which neural precursors express Nestin and the green fluorescent protein (GFP) under the same promoter. We revealed that GDNF significantly (two fold) stimulated axon outgrowth (p < 0.05), but not BDNF or NGF. It is well-known that axon growth can be stimulated by activated glial cells that fulfill a trophic function for regenerating nerves. For this reason, we evaluated the number of Nestin-GFP-positive cells that migrated from the DRG into the Matrigel in our 3D ex vivo explant model. We found that NGF and GDNF, but not BDNF, stimulated the migration of Nestin-GFP cells compared to the control (p < 0.05). On the basis of the aforementioned finding, we concluded that GDNF had the greatest stimulating potential for axon regeneration, as it stimulated not only the axon outgrowth, but also glial cell migration. Although NGF significantly stimulated glial cell migration, its effect on axon growth was insufficient for axon regeneration.Biomedicines 2020, 8, 49 2 of 13 (ECM) that surrounds the cells and creates the microenvironment in vivo [6,8]. The lack of the proper cell-cell and cell-matrix contacts results in change of gene and protein expression profiles [9]. These can adversely affect cell morphology, cell cycle progression, cell survival, and intracellular signaling, potentially resulting in false positive or false negative data acquisition [8,10].In 2D culturing systems, the bioavailability of substances is difficult to evaluate [11]. All cells in a monolayer in 2D culturing conditions simultaneously receive the same dose of a tested agent, whereas in vivo there is a gradient of a tested agent that penetrates the matrix and several layers of cells in a tissue [12]. 3D cultures allow for the assessment of the parameters of a gradual diffusion of tested agents through the gel [6,11].Primary neural cell cultures represent a modern challenge in cell biology, as mature neurons do not undergo cell division in vitro, making it complicated to obtain a sufficient number of cells for experiments [13]. Cell survival is usually low, and neural cell cultures from DRG can be maintained for only 5-7 days, provided that soluble factors that increase survival are added [14]. This is one of the complications in result interpretation when...

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Section: Introductionmentioning

confidence: 99%

Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine

et al. 2020

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“…In addition, scar tissue that develops on site of the injury mechanically prevents axonal extension and as such may affect recovery adversely. Interruption of mechanical transmission and microvasculature in nerve may occur in crush injuries (Sayad Fathi and Zaminy, 2017[38]). As a result, reperfusion leads to pooling of oxygen and nutrients that result in the formation of free radicals.…”

Section: Discussionmentioning

confidence: 99%

Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats

Kasmaie

Jahromi

Gazor

et al. 2019

EXCLI Journal; 18:Doc653; ISSN 1611-2156

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“…The quality and speed of nerve regeneration is improved when occurring in a well-vascularized site and in the presence of small amounts of scar tissue. Besides mechanical factors, the time elapsed between injury and complete repair and its functional recuperation prognosis depend on factors such as the age of the patient, the type of nerve, the site of the nerve that was injured, the cause of the injury and effect on neighboring tissues resulting from the injury [1,2,41,42]. Nonetheless, even when endogenous repair mechanisms are effective, regenerated nerves often present thinner myelin sheets and shorter nodal lengths and result in functional deficits [43].…”

Section: Wallerian Degeneration Endogenous Regeneration and Responsmentioning

confidence: 99%

“…Peripheral nerve injuries result in temporary or permanent interruption of the connection between the nervous system and the effector organ, a phenomena defined as denervation, leading to functional changes and, ultimately, atrophic events [1]. These injuries bear significant impact to patients' health and well-being at both functional/physiological and psychological levels [2].…”

Section: Introductionmentioning

confidence: 99%

Biomaterials and Cellular Systems at the Forefront of Peripheral Nerve Regeneration

Alvites¹,

Branquinho²,

Caseiro³

et al. 2020

Peripheral Nerve Disorders and Treatment

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Peripheral nerve injuries remain a common clinical complication, and currently available therapies present significant limitations, often resulting in poor and suboptimal outcomes. Despite significant developments in microsurgical approaches in the last decades, no effective treatment options have been disclosed. Current research focuses on the optimization of such microsurgical techniques and on their combination with other pro-regenerative factors, such as mesenchymal stem cells or biomaterials. Mesenchymal stem cells present a remarkable capacity for bioactive molecule production that modulates inflammatory and regenerative processes, stimulating peripheral nerve regeneration. In parallel, efforts have been directed towards the development of biomaterial nerve guidance channels and nerve conduits. These biomaterials have been optimized in terms of biodegradability, ability to release bioactive factors, incorporation of cellular agents, and internal matrix architecture (to enable cellular migration and mimic native tissue morphology and to generate and bear specific electrical activity). The current literature review presents relevant advances in the development of mesenchymal stem cell and biomaterial-based therapeutic approaches aiming at the peripheral nerve tissue regeneration in diverse lesion scenarios, also exploring the advances achieved by our research group in this field in recent years.

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Stem cell therapy for nerve injury

Cited by 48 publications

References 112 publications

Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine

Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine

Comparison of melatonin and curcumin effect at the light and dark periods on regeneration of sciatic nerve crush injury in rats

Biomaterials and Cellular Systems at the Forefront of Peripheral Nerve Regeneration

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