Stem Cell Strategies in Promoting Neuronal Regeneration after Spinal Cord Injury: A Systematic Review

Bonosi, Lapo; Silven, Manikon Poullay; Biancardino, Antonio Alessandro; Sciortino, Andrea; Giammalva, Giuseppe Roberto; Scerrati, Alba; Sturiale, Carmelo Lucio; Albanese, Alessio; Tumbiolo, Silvana; Visocchi, Massimiliano; Iacopino, Domenico Gerardo; Maugeri, Rosario

doi:10.3390/ijms232112996

Cited by 8 publications

(8 citation statements)

References 118 publications

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“…The strategy of cell-based therapy for SCI became particularly attractive after the publication of the seminal work of Takahashi and Yamanaka, describing the approach to reprogram somatic cells into a pluripotent state via forced expression of several transcriptional factors (TFs) [44]; this work led to a "gold rush"-like era of extensive efforts in SC-based therapy research and development. Since then, significant progress in the management of neurotrauma and SCI in particular was achieved by applying SCs as a therapeutic tool, including not only widely used MSCs but also the SC-derived biologically active secretome, induced pluripotent stem cells (iPSCs), and directly reprogrammed multipotent neural stem cells (drNSCs) or neural progenitor cells (drNPCs) capable of giving rise to neurons, astrocytes, and oligodendrocytes [45][46][47]. A detailed comparison of the several types of SCs in the context of SCI cell therapy can be found in a recent encyclopedic review by Shao A. et al [48], and, hereafter, we focus on drNPCs.…”

Section: Stem Cell Therapy For Scimentioning

confidence: 99%

Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury

Chudakova,

Samoilova,

Chekhonin

et al. 2023

Cells

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Spinal cord injury (SCI) is a medical condition affecting ~2.5–4 million people worldwide. The conventional therapy for SCI fails to restore the lost spinal cord functions; thus, novel therapies are needed. Recent breakthroughs in stem cell biology and cell reprogramming revolutionized the field. Of them, the use of neural progenitor cells (NPCs) directly reprogrammed from non-neuronal somatic cells without transitioning through a pluripotent state is a particularly attractive strategy. This allows to “scale up” NPCs in vitro and, via their transplantation to the lesion area, partially compensate for the limited regenerative plasticity of the adult spinal cord in humans. As recently demonstrated in non-human primates, implanted NPCs contribute to the functional improvement of the spinal cord after injury, and works in other animal models of SCI also confirm their therapeutic value. However, direct reprogramming still remains a challenge in many aspects; one of them is low efficiency, which prevents it from finding its place in clinics yet. In this review, we describe new insights that recent works brought to the field, such as novel targets (mitochondria, nucleoli, G-quadruplexes, and others), tools, and approaches (mechanotransduction and electrical stimulation) for direct pro-neural reprogramming, including potential ones yet to be tested.

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Section: Stem Cell Therapy For Scimentioning

confidence: 99%

Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury

Chudakova,

Samoilova,

Chekhonin

et al. 2023

Cells

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“…A., 2015). Each typical type of stem cell treatment has its own pros and cons (Bonosi, L. et al, 2022). NSC can secrete neuroprotective cytokines like brain-derived neurotropic factors (BDNF) and enhance cell proliferation as well as myelination (Bonosi, L. et al, 2022).…”

Section: Stem Cell Therapy In Scimentioning

confidence: 99%

“…Despite multiple therapeutic strategies such as surgical decompression, therapeutic hypothermia and drug treatment have achieved different degrees of success, these current treatments can only solve one single aspect or a few aspects of events and curative effect is still elusive (Gazdic, M. et al, 2018). Over the past decades, various stem cell lines like neural stem cells (NSC) have been applied to preclinical models and clinical trials, and each cell line has its own pros and cons (Bonosi, L. et al, 2022). Thus, in recent years more and more researchers focus on combination therapy which involves stem cell transplantation and other strategies like biomaterials, magnetic stimulation or electric stimulation, to discover a reliable and effective treatment for SCI (Zheng, Y., Mao, Y. R., Yuan, T. F., Xu, D. S. & Cheng, L. M., 2020;Zeng, Y. S. et al, 2022;Chen, X. et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Spinal Cord Injury: Pathophysiology, Neural Stem Cell Treatment and Its Combination with Other Strategies

Chen

2023

JIMR

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Spinal cord injury is associated with the damage to neural circuits and disruption of neural pathways, leading to irreversible long-term complications in terms of physical and mental health. Traditional treatments mainly include surgical decompression and pharmacotherapy whereas none of them could attenuate or even alleviate long-term complications following SCI. This is largely due to complicated pathophysiological process in SCI which includes primary injury and secondary injury. Primary injury is defined as direct mechanical damage on the spinal cord in the initial time course of injury. Secondary injury occurs a few hours after primary injury and it could persist for longer time, promoting a catastrophe of degenerative pathophysiological process in spinal cord and related tissues. Although currently there is no effective cure strategies for SCI, some recent studies have shown that stem cell therapy combined with other strategies is able to enhance neurofunctional recovery and neural stem cell line is one of the stem cell lines which show convincing therapeutic effects (Huang, L., Fu, C., Xiong, F., He, C. & Wei, Q., 2021). Biomaterials can work as carriers which help deliver nutrient biomolecules to help NSC survive and differentiate to more functional cells or as scaffolds which provide structural bridges to lesion site for NSC migration and tissue regeneration (Vismara, I., Papa, S., Rossi, F., Forloni, G. & Veglianese, P., 2017). In addition, the basic principles of magnetic stimulation and electric stimulation are similar and they all involve producing electrical current on brain or spinal cord to modulate brain or spinal cord activity. It has been revealed that electric stimulation and repetitive magnetic stimulation is associated with neuroplasticity which may reduce inappropriate lateral sprouting resulting from NSC therapy, making them become potential complementary strategies to NSC therapy as well (Kricheldorff, J. et al., 2022).

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“…Following the primary injury, a cascade of pathophysiological events results in altered neuronal homeostasis, apoptosis, and tissue destruction. SCI is pathophysiologically grouped into primary and secondary injuries and where the acute phase timeline is <48 h, the subacute is between 48 h to 14 days, the intermediate phase is between 14 days to 6 months, and the chronic phase is >6 months [7][8][9]. In this context, the current clinical practice focuses on surgical decompression (with no clear indication about the correct timing for surgical decompression) and, eventually, mechanical stabilization with rods and screws, followed by a pharmacological intervention such as high-dose methylprednisolone.…”

Section: Introductionmentioning

confidence: 99%

An Insight into the Prospects and Drawbacks of Stem Cell Therapy for Spinal Cord Injuries: Ongoing Trials and Future Directions

Khan,

Ahmed,

Ahsan

et al. 2023

Brain Sciences

Self Cite

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Spinal cord injury (SCI) is a devastating neurological disorder that has a substantial detrimental impact on a person’s quality of life. The estimated global incidence of SCI is 40 to 80 cases per million people and around 90% of cases are traumatic. Various etiologies can be recognized for SCI, and post-traumatic SCI represents the most common of these. Patients worldwide with SCI suffer from a persistent loss of motor and sensory function, which affects every aspect of their personal and social lives. Given the lack of effective treatments, many efforts have been made to seek a cure for this condition. In recent years, thanks to their ability to regenerate tissue and repair lost or damaged cells, much attention has been directed toward the use of stem cells (embryonic, induced pluripotent, mesenchymal, hematopoietic), aimed at restoring the functional integrity of the damaged spinal cord and improving a functional recovery including sensory and motor function. In this paper, we offer an overview of the benefits and drawbacks of stem cell therapy for SCI based on clinical evidence. This report also addresses the characteristics of various stem cell treatments, as well as the field’s likely future. Each cell type targets specific pathological characteristics associated with SCI and demonstrates therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation pathways. SCI accompanied by complex pathological processes cannot be resolved by single treatment measures. Stem cells are associated with the adjustment of the expression of neurotrophic factors that help to achieve better nutrition to damaged tissue. Single-cell treatments have been shown in some studies to provide very minor benefits for SCI in multiple preclinical studies and a growing number of clinical trials. However, SCI damage is complex, and many studies are increasingly recognizing a combination approach such as physical therapy, electrical stimulation, or medication therapy to treatment.

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Stem Cell Strategies in Promoting Neuronal Regeneration after Spinal Cord Injury: A Systematic Review

Cited by 8 publications

References 118 publications

Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury

Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury

Spinal Cord Injury: Pathophysiology, Neural Stem Cell Treatment and Its Combination with Other Strategies

An Insight into the Prospects and Drawbacks of Stem Cell Therapy for Spinal Cord Injuries: Ongoing Trials and Future Directions

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