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Transmission electron microscopy (TEM) of the injured sciatic nerve at 12-week transplantation. (a) TEM of ultrathin cross section of the normal sciatic nerve. Individual axons were surrounded by dark concentric linings of compact myelin sheaths. (b) TEM of the central zone of the injured site in the eGFP-SCsN transplanted group. Axons were also surrounded by compact myelin sheaths. Unlike in normal controls, axon diameters were fairly diverse. Small and loose myelin sheaths were also noted (arrows). (c) TEM of the central zone of the injured site in the eGFP-SCsI group. Axon diameters and myelin sheath thickness were diverse and smaller than eGFP-SCsN group, and unmyelinating Schwann cells (white arrows) were seldom observed. The space between myelinated nerve fibers was occupied by endoneurium-like cellular structures and fibrocyte/fibroblasts were observed (black arrowheads). A, axons; M, myelin sheath.
Source publication
Purpose
The fate and function of the induced Schwann cells (iSCs) like cells from adipose tissue have not been critically evaluated in vivo after transplantation. The objective of this study is to compare the fate of iSCs with naïve SCs (nSCs) after transplantation into the lesion sites of sciatic nerve, respectively.
Methods
Adipose-derived stem...
Citations
... 7,8 However, the immunogenicity of allogenic SCs limits their use, and autologous SC transplantation is hindered by prolonged expansion in vitro and morbidities resulting from the sacrifice of donor nerves, which limits the source for harvest in clinical scenario. Other promising routes to utilize bioactive cues of SCs include transplantation of SC-like cells, [9][10][11] SC-derived biomaterials, 9,12 or augmentation of local SC recruitment. [13][14][15] SC-like cells require induction processes for stem cells of various origins to differentiate into SC-like cells and face the challenges to maintain their phenotype in vivo. ...
Peripheral nerve injuries are commonly occurring traumas of the extremities; functional recovery is hindered by slow nerve regeneration (<1 mm/day) following microsurgical repair and subsequent muscle atrophy. Functional recovery after peripheral nerve repair is highly dependent on local Schwann cell activity and axon regeneration speed. Herein, to promote nerve regeneration, paracrine signals of adipose-derived stem cells were applied in the form of extracellular vesicles (EVs) loaded in a thermosensitive hydrogel (PALDE) that could solidify rapidly and sustain high EV concentration around a repaired nerve during surgery. Cell experiments revealed that PALDE hydrogel markedly promotes Schwann-cell migration and proliferation and axon outgrowth. In a rat sciatic nerve repair model, the PALDE hydrogel increased repaired-nerve conduction efficacy; contraction force of leg muscles innervated by the repaired nerve also recovered. Electromicroscopic examination of downstream nerves indicated that fascicle diameter and myeline thickness in the PALDE group (1.91 ± 0.61 and 1.06 ± 0.40 μm, respectively) were significantly higher than those in PALD and control groups. Thus, this EV-loaded thermosensitive hydrogel is a potential cell-free therapeutic modality to improve peripheral-nerve regeneration, offering sustained and focused EV release around the nerve-injury site to overcome rapid clearance and maintain EV bioactivity in vivo.
... As ADSCs emerge from the mesodermal embryonic layer, they exhibit higher adherence, immune phenotype, self-renewal, and multipotent properties in the predifferentiated stage. As such, they can be used as a reservoir for different cell lineages including adipocytes, fibrocytes, osteocytes, chondrocytes, skeletal, smooth, and cardiac myocytes, hepatocytes, and neuronal cells [34][35][36][37][38][39][40]. Cardiac infusion of an ADSCs MI rat model shows improved left ventricular ejection To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter SPi. ...
The well-accepted dogma that the mammalian heart has poor regeneration efficiency upon injury laid the foundation for cardiac cell therapy. With the advancement in various cell therapies, cell reprogramming and bioengineering methods such as augmenting innate cell-proliferation capacity, direct reprogramming of progenitor cells into cardiomyocytes, direct delivery of potent cardiomyocytes for tissue regeneration, and iPSC-derived stem cell therapy have gained much attention. However, the translatability of these approaches into clinical settings is limited. The nonpredictive onset of mutational changes, genomic challenges, and pathological remodeling in the cardiac cells has generated challenges to some approaches. With in-depth understanding of basic principles and principles of gene expression, network pathways, transcription factor networks that contribute to vertebrate heart development, cardiomyocyte maturation/differentiation, and methods to augment heart regeneration have the potential to counteract the high morbidity and mortality of cardiovascular disease. Myocardial regeneration is the thrust area of research to repair/regenerate cardiomyocyte loss, which warrants further research to validate its clinical applicability in humans.
... One basic purpose of genetically modification of Schwann cells is for them to produce green fluorescent protein (EGFP), in order to follow their fate and track their role in nerve repair and myelination. Many studies use this methodology (Schmitte et al., 2010;Deng et al., 2014;Zhang et al., 2017). With the intuit of overexpressing a specific GF, Timmer et al. (2003) implanted a silicon tube filled with Matrigel with enclosed transfected Schwann cells to overexpress fibroblast growth factor (FGF-2). ...
Peripheral nerve repair and regeneration remains among the greatest challenges in tissue engineering and regenerative medicine. Even though peripheral nerve injuries (PNIs) are capable of some degree of regeneration, frail recovery is seen even when the best microsurgical technique is applied. PNIs are known to be very incapacitating for the patient, due to the deprivation of motor and sensory abilities. Since there is no optimal solution for tackling this problem up to this day, the evolution in the field is constant, with innovative designs of advanced nerve guidance conduits (NGCs) being reported every day. As a basic concept, a NGC should act as a physical barrier from the external environment, concomitantly acting as physical guidance for the regenerative axons across the gap lesion. NGCs should also be able to retain the naturally released nerve growth factors secreted by the damaged nerve stumps, as well as reducing the invasion of scar tissue-forming fibroblasts to the injury site. Based on the neurobiological knowledge related to the events that succeed after a nerve injury, neuronal subsistence is subjected to the existence of an ideal environment of growth factors, hormones, cytokines, and extracellular matrix (ECM) factors. Therefore, it is known that multifunctional NGCs fabricated through combinatorial approaches are needed to improve the functional and clinical outcomes after PNIs. The present work overviews the current reports dealing with the several features that can be used to improve peripheral nerve regeneration (PNR), ranging from the simple use of hollow NGCs to tissue engineered intraluminal fillers, or to even more advanced strategies, comprising the molecular and gene therapies as well as cell-based therapies.
... It should be noted that ASCs also have the capability to differentiate toward non-mesenchymal cell lineages such as myogenic, neuronal and endothelial [104][105][106][107][108][109]. ...
... Neurogenic. The differentiation of ASCs in vitro toward the neural lineage has also been explored [105,106]. For instance, the treatment of human or rat ASCs with beta-mercaptoethanol results in a rapid transition of cells to neuronal morphology and expression of neuronal markers such as nestin expression, neuron-specific enolase, and neuron protein [82]. ...
... The same results were observed by exposure of ASCs to isobutylmethylxanthine and dibutyryl cAMP or forskolin and butylated hydroxyanisole [118]. In vivo data on the neural potential of ASCs, currently, are limited but promising [106,119]. ...
During the last five years, there has been a significantly increasing interest in adult adipose stem cells (ASCs) as a suitable tool for translational medicine applications. The abundant and renewable source of ASCs and the relatively simple procedure for cell isolation are only some of the reasons for this success. Here, we document the advances in the biology and in the innovative biotechnological applications of ASCs. We discuss how the multipotential property boosts ASCs toward mesenchymal and non-mesenchymal differentiation cell lineages and how their character is maintained even if they are combined with gene delivery systems and/or biomaterials, both in vitro and in vivo.
Chronic musculoskeletal (MSK) pain is one of the most common medical complaints worldwide and musculoskeletal injuries have an enormous social and economical impact. Current pharmacological and surgical treatments aim to relief pain and restore function; however, unsatiscactory outcomes are commonly reported. In order to find an accurate treatment to such pathologies, over the last years, there has been a significantly increasing interest in cellular therapies, such as adipose-derived mesenchymal stem cells (AMSCs). These cells represent a relatively new strategy in regenerative medicine, with many potential applications, especially regarding MSK disorders, and preclinical and clinical studies have demonstrated their efficacy in muscle, tendon, bone and cartilage regeneration. Nevertheless, several worries about their safety and side effects at long-term remain unsolved. This article aims to review the current state of AMSCs therapy in the treatment of several MSK diseases and their clinical applications in veterinary and human medicine.
Introduction: The sciatic nerve is one of the peripheral nerves that is most prone to injuries. After injury, the connection between the nervous system and the distal organs is disrupted, and delayed treatment results in distal organ atrophy and total disability. Regardless of great advances in the fields of neurosurgery, biological sciences, and regenerative medicine, total functional recovery is yet to be achieved.
Areas covered: Cell-based therapy for the treatment of peripheral nerve injuries (PNIs) has brought a new perspective to the field of regenerative medicine. Having the ability to differentiate into neural and glial cells, stem cells enhance neural regeneration after PNIs. Augmenting axonal regeneration, remyelination, and muscle mass preservation are the main mechanisms underlying stem cells’ beneficial effects on neural regeneration.
Expert opinion: Despite the usefulness of employing stem cells for the treatment of PNIs in pre-clinical settings, further assessments are still needed in order to translate this approach into clinical settings. Mesenchymal stem cells, especially adipose-derived stem cells, with the ability of autologous transplantation, as well as easy harvesting procedures, are speculated to be the most promising source to be used in the treatment of PNIs.
