Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection

Ganz, Javier; Shor, Erez; Guo, Shengming; Sheinin, Anton; Arie, Ina; Michaelevski, Izhak; Pitaru, S.; Offen, Daniel; Levenberg, Shulamit

doi:10.3389/fnins.2017.00589

Cited by 26 publications

(25 citation statements)

References 67 publications

(90 reference statements)

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“…Besides, we performed IF assay using anti-BAF45D and anti-MBP antibodies (Figures 3M–R). The results indicate that colocalization of BAF45D (Figures 3M,O,P,R,M1,O1,P1,R1, red) with MBP (Figures 3N,O,Q,R,N1,O1,Q1,R1, green), an oligodendrocyte marker located on myelin sheath membrane (Ganz et al, 2017), was detected in the rat spinal cords.…”

Section: Resultsmentioning

confidence: 87%

BAF45D Downregulation in Spinal Cord Ependymal Cells Following Spinal Cord Injury in Adult Rats and Its Potential Role in the Development of Neuronal Lesions

et al. 2019

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The endogenous spinal cord ependymal cells (SCECs), which form the central canal (CC), are critically involved in proliferation, differentiation and migration after spinal cord injury (SCI) and represents a repair cell source in treating SCI. Previously, we reported that BAF45D is expressed in the SCECs and the spinal cord neurons in adult mice and knockdown of BAF45D fail to induce expression of PAX6, a neurogenic fate determinant, during early neural differentiation of human embryonic stem cells. However, the effects of SCI on expression of BAF45D have not been reported. The aim of this study is to explore the expression and potential role of BAF45D in rat SCI model. In this study, adult rats were randomly divided into intact, sham, and SCI groups. We first explored expression of BAF45D in the SCECs in intact adult rats. We then explored SCI-induced loss of motor neurons and lesion of neurites in the anterior horns induced by the SCI. We also investigated whether the SCI-induced lesions in SCECs are accompanied by the motor neuron lesions. Finally, we examined the effect of BAF45D knockdown on cell growth in neuro2a cells. Our data showed that BAF45D is expressed in SCECs, neurons, and oligodendrocytes but not astrocytes in the spinal cords of intact adult rats. After SCI, the structure of CC was disrupted and the BAF45D-positive SCEC-derivatives were decreased. During the early stages of SCI, when shape of CC was affected but there was no disruption in circular structure of the SCECs, it was evident that there was a significant reduction in the number of neurites and motor neurons in the anterior horns compared with those of intact rats. In comparison, a complete loss of SCECs accompanied by further loss of motor neurons but not neurites was observed at the later stage. BAF45D knockdown was also found to inhibit cell growth in neuro2a cells. These results highlight the decreased expression of BAF45D in SCI-injured SCECs and the potential role of BAF45D downregulation in development of neuronal lesion after SCI in adult rats.

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Section: Resultsmentioning

confidence: 87%

BAF45D Downregulation in Spinal Cord Ependymal Cells Following Spinal Cord Injury in Adult Rats and Its Potential Role in the Development of Neuronal Lesions

et al. 2019

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“…One of the emerging therapeutic routes for neuronal repair is cell therapy where novel populations of cells are introduced into injured sites. [67][68][69] Driving cells or drugs to selected regions of interest in a controlled manner is one of the main challenges toward the success of this approach. Our platform demonstrates the advantages and possibilities of using functional magnetic materials for tissue engineering and neuronal therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Organization of Neural Networks via Micro‐Patterned Devices

Marcus

Indech

Vardi

et al. 2020

Adv Materials Inter

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As most biological tissues, neural networks are organized at the micron-scale, with cells positioned appropriately and arranged in a high spatial resolution. Therefore, an important aspect of creating functional neural networks and network interfaces is the ability to localize neurons and guide nerve cell processes to form predesigned structures at this scale, raising technological challenges. Many studies focus on developing neuronal guidance abilities by using chemical and physical cues. [2,3,11-25] A recent approach for controlling cell motility is by applying magnetic forces. [26-30] Incorporating magnetic nanoparticles (MNPs) within cells turns them into magnetic-sensitive units that can be remotely manipulated through controllable magnetic fields. In previous medical applications MNPs have been used for in vivo tracking of cells by magnetic resonance imaging, [31-34] magnetic cell targeting to sites of tissue damage, [26,35-38] drug delivery, and thermotherapy cancer treatment. [39-43] Magnetic forces have been used to create and orient 3D tissues, [44] to fabricate tubular structures by manipulating magnetically labeled cells [14,45] and to control the delivery of growth factors. [46-48] In the nervous system guiding cells toward target tissue is of special importance, both for neuronal replacement and as a supportive tissue. [49-51] However, magnetic organization of neurons at the single cell level has yet not been demonstrated. In order to form functional networks, there is a need for local control of soma motility and axonal outgrowth, with micron scale resolution. Previously, we fabricated substrates embedded with microarrays of ferromagnetic (FM) pads. [52] FM thin films form magnets with stable in-plane magnetization due to shape anisotropy energies. [53] The in-plane magnetization limited the positioning of cells, demonstrating an attraction of the magnetized cells only to the magnetic poles of the pads due to the magnetic field line distribution (Figure 1). In this study, we design and fabricate micro-patterned multilayered FMs with perpendicular magnetic anisotropy (PMA). Our multilayered structures, inspired by magnetic recording media, [54] show better miniaturization scalability and thermal stability compared to in-plane magnets, [55] and have a substantial magnetization saturation that results in strong magnetic forces. These PMA pads show strong attraction of the MNP-loaded Guiding neuronal migration and outgrowth has great importance for therapeutic applications and for bioelectronics interfaces. Many efforts have been devoted to the development of tools to form predesigned structured neuronal networks. Here, a unique approach to localize cell bodies and direct neurite outgrowth is described based on local magnetic manipulations. Inspired by spintronic devices, a multi-layer deposition process is developed to generate nanometricthick films with perpendicular magnetization that provide stable attraction forces toward the entire magnetic pads. PC12 cells, a common neuronal model, are transform...

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“…Moreover, therapeutic effects of MSCs have been observed in both the acute and chronic phases after SCI. Regarding the route of administration, direct injection to the injured area and intravenous or intrathecal administration of MSCs have led to improved neural regeneration [27][28][29][30][31][32]. Bone marrow mesenchymal stem cells (BM-MSC) is low immunogenicity compared with MSCs from other tissue.…”

Section: Preclinical Stem Cell Therapy For the Treatment Of Spinal Comentioning

confidence: 99%

Stem Cell Therapy for Neurogenic Bladder After Spinal Cord Injury: Clinically Possible?

et al. 2020

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Neurogenic bladder (NB) after spinal cord injury (SCI) is a common complication that inhibits normal daily activities and reduces the quality of life. Regrettably, the current therapeutic methods for NB are inadequate. Therefore, numerous studies have been conducted to develop new treatments for NB associated with SCI. Moreover, a myriad of preclinical and clinical trials on the effects and safety of stem cell therapy in patients with SCI have been performed, and several studies have demonstrated improvements in urodynamic parameters, as well as in sensory and motor function, after stem cell therapy. These results are promising; however, further high-quality clinical studies are necessary to compensate for a lack of randomized trials, the modest number of participants, variation in the types of stem cells used, and inconsistency in routes of administration.

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Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection

Cited by 26 publications

References 67 publications

BAF45D Downregulation in Spinal Cord Ependymal Cells Following Spinal Cord Injury in Adult Rats and Its Potential Role in the Development of Neuronal Lesions

BAF45D Downregulation in Spinal Cord Ependymal Cells Following Spinal Cord Injury in Adult Rats and Its Potential Role in the Development of Neuronal Lesions

Magnetic Organization of Neural Networks via Micro‐Patterned Devices

Stem Cell Therapy for Neurogenic Bladder After Spinal Cord Injury: Clinically Possible?

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