Browsing by Subject "Mesenchymal stem cells"

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    Anti-death strategies against oxidative stress in grafted mesenchymal stem cells
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Woochul, Chang; Byeong-Wook, Song; Jae-Youn, Moon; Min-Ji, Cha; Onju, Ham; Se-Yeon, Lee; Eunmi, Choi; EunHyum, Choi; Ki-Chul, Hwang
    Mesenchymal stem cells (MSCs) possess the potential for use in cell-based therapy for repair of myocardial injury. The therapeutic potential of MSCs is based on the capacity of MSCs to differentiate into cardiac tissue and release paracrine factors. However, a major problem in the clinical application of MSC-based therapy is the poor viability of transplanted MSCs at the site of graft due to harsh microenvironment conditions, such as ischemia and/or anoikis. Ischemia after myocardial infarction (MI) and interaction of MSCs with their niche is associated with increased production of reactive oxygen species (ROS). ROS hinder cell adhesion and induce detachment of cells, which induces anoikis signals in implanted MSCs. Therefore, strategies to regulate oxidative stress following the implantation of MSCs are therapeutically attractive. In this review, we first describe ROS as a major obstacle in MSC-based therapy and focus on manipulation of implanted MSCs to reduce ROS-mediated anoikis.
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    Chondrogenesis of mesenchymal stem cells for cartilage tissue engineering
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Gardner, Oliver F.W.; Archer, Charles W.; Alini, Mauro; Stoddart, Martin J.
    Despite its remarkable ability to resist mechanical loading, articular cartilage is not capable of mounting a useful reparative reaction in response to damage caused by trauma or disease. As a result numerous surgical and medical approaches have been developed to aid the healing of articular cartilage. Despite the success of surgical techniques such as microfracture, recently attentions have been turned to cell based therapies such as autologous chondrocyte implantation (ACI). ACI has produced encouraging results, however better results may be achievable through an evolution of this surgical approach. Since the first generation of ACI techniques changes have been made in the technique e.g. the introduction of collagen membranes instead of periosteal flaps, and more recently the use of collagen scaffolds for cellular delivery. The procedure has also moved on from being performed as an open operation and can now be performed arthroscopically. Despite these advances the procedure still uses chondrocytes harvested from the joint being repaired. These cells are vulnerable to dedifferentiation during the required in vitro expansion, and as a result may not be capable of producing repair tissue once implanted back into the joint. Mesenchymal stem cells (MSCs) may provide a dedifferentiation resistant alternative to chondrocytes. MSCs would also allow for the use of one arthroscopic operation on the affected joint, as opposed to the two operations that are currently required for ACI.
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    Current understanding of orofacial tissue derived mesenchymal stem cells: an immunological perspective
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Ding, Gang; Niu, Jianyi; Wei, Fulan
    Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells able to differentiate into multiple lineages, holding the potential for replacing damaged and diseased tissues by tissue regeneration and immunomodulatory functions. So far, MSCs have been successfully isolated and characterized from a variety of orofacial tissues, including dental pulp, periodontal ligament, root apical papilla, gingiva, etc. In addition to their self-renewal and multipotent differentiation properties, these orofacial tissue derived MSCs are also capable of profound immunomodulatory effects in vitro and in vivo, thus providing a foundation for their utilization in allogeneic application and in treating autoimmune diseases and inflammatory disorders. In this paper, we will review the current research progress of the immunomodulatory properties of orofacial tissue derived MSCs and the underlying mechanisms, emphasizing the effect of these MSCs on immune cells, which will facilitate the use of such cells in clinical treatment.
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    Effect of short-term betamethasone administration on the regeneration process of tissue-engineered bone
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Chihara, Takahiro; Zhang, Yiming; Li, Xianqi; Shinohara, Atsushi; Kagami, Hideaki
    Local inflammation at the transplanted site of tissue-engineered bone may cause apoptosis of the transplanted cells, thus negatively affecting bone regeneration. To maximize the efficacy of bone tissue engineering, the local effect of short-term corticosteroid administration at the transplanted site of tissue- engineered bone was studied with respect to the expression of inflammatory cytokines. Compact bone- derived cells from mouse leg bones were isolated, cultured and seeded onto β-tricalcium phosphate granules. The constructs were transplanted to the back of syngeneic mice. Betamethasone sodium phosphate was administered intraperitoneally to an experimental (betamethasone) group, whereas the same amount of saline was administered to a control group. When betamethasone was administered three times (immediately after operation and 12 hours and 24 hours after transplantation), the number of SP7/osterix-positive osteoblasts was larger in the betamethasone group. Three times of betamethasone administration (immediately after operation and 12 hours and 24 hours after transplantation) did not change the number of apoptotic cells and osteoclasts, but showed a slight upregulation of IL-4 and a downregulation of IL-6. However, 7 doses of betamethasone administration (over 7 consecutive days) increased the number of apoptotic cells and osteoclasts, which was correlated with a downregulation of IL-4 and an upregulation of IL-6. TNF-α expression levels showed no significant differences between the two groups. The results showed beneficial effects of 3 betamethasone administrations for bone regeneration therapy but contrary effects when betamethasone was administered 7 times due to the downregulation of anti- inflammatory cytokines (IL-4) and the upregulation of inflammatory cytokines (IL-6). As a conclusion, our results suggested the importance of the cautious usage of corticosteroids to control local inflammation at transplanted sites in bone tissue engineering
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    Emerging relationship between CFTR, actin and tight junction organization in cystic fibrosis airway epithelium
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Castellani, Stefano; Favia, Maria; Guerra, Lorenzo; Carbone, Anna Lucia; Abbattiscianni, Anna Claudia; Di Gioia, Sante; Casavola, Valeria; Conese, Massimo
    Cystic fibrosis (CF), one of the most common genetic disorders affecting primarily Caucasians, is due to mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, encoding for a chloride channel also acting as regulator of other transmembrane proteins. In healthy subjects, CFTR is maintained in its correct apical plasma membrane location via the formation of a multiprotein complex in which scaffold proteins (such as NHERF1) and signaling molecules (such as cAMP and protein kinases) guarantee its correct functioning. In CF, a disorganized and dysfunctional airway epithelium brings an altered flux of ions and water into the lumen of bronchioles, consequent bacterial infections and an enormous influx of inflammatory cells (mainly polymorphonuclear neutrophils) into the airways. Recent evidence in healthy airway cells supports the notion that CFTR protein/function is strictly correlated with the actin cytoskeleton and tight junctions status. In CF cells, the most frequent CFTR gene mutation, F508del, has been shown to be associated with a disorganized actin cytoskeleton and altered tight junction permeability. Thus, the correct localization of CFTR on the apical plasma membrane domain through the formation of the scaffolding and signaling complex is likely fundamental to determine a physiological airway epithelium. The correction of CFTR mutations by either gene or drug therapies, as well as by stem cell-based interventions, can determine the resumption of a physiological organization of actin stress fibers and TJ structure and barrier function, further indicating the close interrelationship among these processes.
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    Extracellular vesicles derived from mesenchymal stem cells: A platform that can be engineered
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Qin, Bo; Zhang, Qi; Chen, Dan; Yu, Hai-yang; Luo, Ai-xiang; Suo, Liang-peng; Cai, Yan; Cai, De-yang; Luo, Jia; Huang, Ju-fang; Xiong, Kun
    y. Mesenchymal stem cells play an important role in tissue damage and repair. This role is mainly due to a paracrine mechanism, and extracellular vesicles (EVs) are an important part of the paracrine function. EVs play a vital role in many aspects of cell homeostasis, physiology, and pathology, and EVs can be used as clinical biomarkers, vaccines, or drug delivery vehicles. A large number of studies have shown that EVs derived from mesenchymal stem cells (MSC-EVs) play an important role in the treatment of various diseases. However, the problems of low production, low retention rate, and poor targeting of MSC-EVs are obstacles to current clinical applications. The engineering transformation of MSC-EVs can make up for those shortcomings, thereby improving treatment efficiency. This review summarizes the latest research progress of MSC-EV direct and indirect engineering transformation from the aspects of improving MSC-EV retention rate, yield, targeting, and MSC-EV visualization research, and proposes some feasible MSC-EV engineering methods of transformation.
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    Human Wharton’s jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of antiinflammatory and neurotrophic factors
    (Springer Nature, 2018-11-02) Millán-Rivero, J.E; Nadal-Nicolás, F.M.; García-Bernal, D.; Sobrado-Calvo, P.; Blanquer, M.; Moraleda, J.M.; Vidal-Sanz, M.A.; Agudo-Barriuso, M.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
    El artículo muestra los resultados del estudio de la capacidad neuroprotectora de las células mesenquimales derivadas de cordón umbilical (CMCU) sobre las células ganglionares de la retina (CGR) tras axotomía por aplastamiento del nervio óptico. Se quería saber, no solo si existía efecto neuroprotector, si no también si el trasplante de estas células tenía algún efecto tóxico en retina, y dilucidar los posibles mecanismos a través de los cuales se produjeran estos efectos. En una primera parte del estudio, demostramos que las CMCU suprimen la proliferación de células T e inhiben la producción de citocinas proinflamatorias, confirmando que su efecto inmunomodulador es mayor que el de las células mesequimales derivadas de médula ósea. También observamos que tras la inyección intravítrea de CMCU, estas se integran en la capa de CGR, extendiéndose por toda la retina, observándose una reducción importante a los 30 días, y no observando la formación de tumoración. En retinas intactas no se observó efecto tóxico sobre las CGR, si bien sí hubo alteración de la arquitectura de la retina por la infiltración masiva de células Iba1+ (microglía o macrófagos), que se reduce mucho a los 30 días y da señales de restauración de dicha arquitectura. Por otra parte, en retinas axotomizadas se encontró un aumento muy importante de la supervivencia de las CGR de los animales tratados.
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    Immunomodulatory functions of mesenchymal stem cells and possible mechanisms
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Qing; Ding, Gang; Xu, Xin
    In addition to their well-studied self-renewal capabilities and multipotent differentiation properties, mesenchymal stem cells (MSCs) have been reported to possess profound immunomodulatory functions both in vitro and in vivo. More and more studies have shown that MSCs are capable of interacting closely with almost all subsets of immune cells, such as T cells, B cells, dendritic cells, natural killer cells, macrophages, and neutrophils etc. The immunomodulatory property of MSCs may shed light on the treatment of a variety of autoimmune and inflammation-related diseases. In this article, we will review the studies on the immunomodulatory and anti-inflammatory functions of MSCs and the mechanisms responsible for the interaction between immune cells and MSCs, which could improve the development of promising approaches for cellmediated immune therapies.
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    Mesenchymal stem cell-mediated treatment of oral diseases
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Liu, Yi; Hu, Jingchao; Wang, Songlin
    In the oral maxillofacial region, there are significant demands for repairing severe tissue defects caused by congenital malformations, oncologic resection, post-traumatic loss, and pathologic degenerative destruction such as periodontitis. Mesenchymal stem cells (MSCs) are adult stem cells whose multipotency has been investigated for therapeutic applications. This review highlights the main MSCs involved in the tissue regeneration of oral maxillofacial region and recent advances in dental MSCbased tissue regeneration and treatments in this region. MSCs isolated from oral maxillofacial sources have higher proliferation rates and are more capable of forming bone and dental tissues. Large animal models of oral diseases or defects were established and treated with MSCs. Miniature pigs or dogs more closely mimic disease in humans and provide a useful means for translating research into clinical applications. MSCs exert other beneficial effects, including immunomodulation and paracrine processes. The immunoregulatory properties of MSCs facilitate their application to oral diseases and tissue regeneration. Besides autologous MSCs being an excellent cell source for tissue engineering and regenerative medicine, allogeneic MSC-based treatment also provides a safe and effective therapeutic modality, the use of allogeneic MSCs in highly standardized clinical trials could lead to a better understanding of their real-life applications, which sheds light on potential clinical applications for treating oral diseases.
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    Mesenchymal stem cells: from the perivascular environment to clinical applications
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Vezzani, Bianca; Pierantozzi, Enrico; Sorrentino, Vincenzo
    Adult stem cells represent a fundamental biological system that has fascinated scientists over the last decades, and are currently the subject of a large number of studies aimed at better defining the properties of these cells, with a prominent focus on improving their application in regenerative medicine. One of the most used adult stem cells in clinical trials are mesenchymal stem cells (MSCs), which are multipotent cells able to differentiate into mature cells of mesodermal lineages. Following the initial studies on MSCs isolated from bone marrow, similar cells were also isolated from a variety of fetal and adult human tissues. Initially considered as identical and equipotent, MSCs from tissues other than bone marrow actually display differences in terms of their plastic abilities, which can be ascribed to the tissue of origin and/or to the procedures used for their isolation. Moreover, results from additional studies suggest that cultured MSCs represent the in vitro version of a subset of in vivo resident cells localized in the perivascular environment. In this review, we will focus our attention on MSCs from tissues other than bone marrow, their in vivo localization and their current applications in clinics.
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    Might the Masson trichrome stain be considered a useful method for categorizing experimental tendon lesions?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Martinello, Tiziana; Pascoli, Francesco; Caporale, Giovanni; Perazzi, Anna; Iacopetti, Ilaria; Patruno, Marco
    Strain injuries of tendons are the most common orthopedic injuries in athletic subjects, be they equine or human. When the tendon is suddenly damaged, an acute inflammatory phase occurs whereas its repetitive overloading may cause chronic injuries. Currently the criteria used for grading injuries are general and subjective, and therefore a reliable grading method would be an improvement. The main purpose of this study was to assess qualitatively the histological pattern of Masson trichrome stain in healthy and injured tendons; indeed, the known “paradox” of Masson staining was used to create an evaluation for the matrix of tendons, following experimental lesions and natural repair processes. A statistically significant difference of aniline-staining between healthy and lesioned tendons was observed. Overall, we think that the Masson staining might be regarded as an informative tool in discerning the collagen spatial arrangement and therefore the histological characteristics of tendons.
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    PRP and MSCs on tenocytes artificial wound healing: an in vitro study comparing fresh and frozen PRP
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Veronesi, Francesca; Pagani, Stefania; Torricelli, Paola; Filardo, Giuseppe; Cavallo, Carola; Grigolo, Brunella; Fini, Milena
    Tendon tissue has poor regenerative capacity due to its low vascularization, cell density and extracellular matrix (ECM) production. Therefore, tendon injuries are an increasing clinical problem because of the formation of scar tissue with traditional therapies. Regenerative medicine aims at triggering a healing response through the use of biological treatments such as mesenchymal stromal cells (MSCs) and growth factors (GFs). MSCs show several advantages in tendon clinical setting, while platelet rich plasma (PRP) has gained popularity because of its high GF concentration, although its applications in the tendon clinical setting are still controversial. The aim of the present study was to evaluate a combined treatment of MSCs and PRP in an in vitro microwound model of tendon injuries. In addition, fresh and frozen PRP were compared. Single human tenocytes cultures or co-cultures with bone marrow derived MSCs (BMSCs) were set up with or without human PRP, fresh or frozen. After 24 hours of culture, it was observed that MSCs alone significantly increased tenocyte migration speed, microwound healing rate, fibronectin, collagen I and aggrecan production. These effects were enhanced by the combination with PRP, fresh being more effective than frozen PRP. In addition, the number of MSCs and tenocytes inside the microwound was significantly increased, especially with fresh PRP. In conclusion, the combination of MSCs and PRP, especially the fresh one, increases tenocytes and MSC migration speed, as well as ECM protein production compared to the use of MSCs alone
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    Signaling molecules and pathways involved in MSC tumor tropism
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Ho, Ivy AW; Lam, Paula YP
    Human bone marrow is a reservoir containing cells with different self-renewal capabilities, such as mesenchymal stem cells (MSC) and hematopoeitic stem cells (HSC). MSC in particular have been increasingly used in preclinical and clinical treatment of tissue regenerative disorder. Understanding the molecular mechanisms underlying MSC homing and mobilization is critical to the design of rational cell therapy approaches. In this review, we will discuss the key molecular mechanisms that govern the homing of MSC to bone marrow, the mobilization of MSC to tumors and injured sites via circulation, and strategies that enhance MSC migration.
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    The effects of cigarette smoking and nicotine on the therapeutic potential of mesenchymal stem cells
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Harrell, Carl Randall; Djonov, Valentin; Volarevic, Vladislav
    Due to their immunoregulatory properties and capacity for multi-lineage differentiation, mesenchymal stem cells (MSCs) have been used as new therapeutic agents in regenerative medicine. Numerous lifestyle habits and behavioral risk factors may modulate metabolic and cell growth signaling pathways in MSCs, affecting their phenotype and function. Accordingly, identification of these factors and minimization of their influence on viability and function of transplanted MSCs may greatly contribute to their better therapeutic efficacy. A large number of experimental and clinical studies have demonstrated the detrimental effects of cigarette smoke and nicotine on proliferation, homing, chondrogenic and osteogenic differentiation of MSCs. Cigarette smoke down-regulates expression of chemokine receptors and modulates activity of antioxidative enzymes in MSCs, while nicotine impairs synthesis of transcriptional factors that regulate the cell cycle, metabolism, migration, chondrogenesis and osteogenesis. In this review article, we summarize current knowledge about molecular mechanisms that are responsible for cigarette smoke and nicotine-dependent modulation of MSCs' therapeutic potential.
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    Transplantation of mesenchymal stem cells preserves podocyte homeostasis through modulation of parietal epithelial cell activation in adriamycin-induced mouse kidney injury model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Aslam, Rukhsana; Hussain, Ali; Cheng, Kang; Kumar, Vinod; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.
    To determine the role of the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) in podocyte renewal, we studied BALB/C mice with or without adriamycin-induced acute kidney injury. MSCs were transplanted ectopically under the capsule of the left kidney or into the peritoneal cavity after the onset of kidney injury to test their local or systemic paracrine effects, respectively. Adriamycin produced increases in urine protein: creatinine ratios, blood urea nitrogen, and blood pressure, which improved after both renal subcapsular and intraperitoneal MSCs transplants. The histological changes of adriamycin kidney changes regressed in both kidneys and in only the ipsilateral kidney after intraperitoneal or renal subcapsular transplants indicating that the benefits of transplanted MSCs were related to the extent of paracrine factor distribution. Analysis of kidney tissues for p57-positive podocytes showed that MSC transplants restored adriamycin-induced decreases in the abundance of these cells to normal levels, although after renal subcapsular transplants these changes did not extend to contralateral kidneys. Moreover, adriamycin caused inflammatory activation of PECs with coexpression of CD44 and phospho-ERK, which was normalized in both or only ipsilateral kidneys depending on whether MSCs were transplanted in the peritoneal cavity or subcapsular space, respectively
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    Treatments of the injured tendons in Veterinary Medicine: from scaffolds to adult stem cells
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Patruno, Marco; Martinello, Tiziana
    In order to treat frequently occurring conditions such as traumatic rupture or over-strain tendinopathies, the techniques of tissue engineering and cell-based therapies have become an accepted modus operandi since other available remedies appear to be ineffective in restoring the original structure and function of the injured tissue. However, the mechanisms accounting for the effectiveness of novel regenerative approaches in treating equine tendon and ligament injuries remain poorly characterised. In this review we summarize and discuss the most significant results of our research regarding bioscaffold technology for treating complete tendon tears and the use of adult stem cells for treating tendon lesions induced by over-strain. Histol Histopathol 29, 417-422 (2014)
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    Ultrastructural morphology of equine adipose-derived mesenchymal stem cells
    (Murcia : F. Hernández, 2010) Pascucci, Luisa; Mercati, Francesca; Marini, Carla; Ceccarelli, Piero; Dall’Aglio, C.; Pedini, Vera; Gargiulo, Anna María
    Mesenchymal stem cells are a virtually ubiquitous population of adult stem cells, able to differentiate into various tissue lineages. As they are multipotent and easy to grow in culture, they are at present considered very attractive candidates for tissue repair and gene therapy. With the exception of a few reports, mesenchymal stem cell morphology has been widely disregarded in the past years. In this paper we discuss the establishment of mesenchymal stem cell cultures from equine adipose tissue and describe their fine structure by transmission electron microscopy. The cultured cells revealed a fibroblastoid appearance and were characterized by an eccentric nucleus with multiple nucleoli, dense cytoplasm rich in ribosomes, a rough endoplasmic reticulum with dilated cisternae, elongated mitochondria and heterogeneous vacuolar inclusions. In addition, they were often interconnected by adhesion structures located on the cell body and on cytoplasmic processes contacting other cells. The features observed are evocative of an undifferentiated cellular phenotype and of an intense synthetic and metabolic activity.
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    Umbilical cord revisited: from Wharton’s jelly myofibroblasts to mesenchymal stem cells
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Corrao, Simona; La Rocca, Giampiero; Lo Iacono, Melania; Corsello, Tiziana; Farina, Felicia; Anzalone, Rita
    The umbilical cord (UC) is an essential part of the placenta, contributing to foetal development by ensuring the blood flow between mother and foetus. The UC is formed within the first weeks of gestation by the enclosure of the vessels (one vein and two arteries) into a bulk of mucous connective tissue, named Wharton’s jelly (WJ) and lined by the umbilical epithelium. Since their first identification, cells populating WJ were described as unusual fibroblasts (or myofibroblasts). Recent literature data further highlighted the functional interconnection between UC and the resident cells. The UC represents a reservoir of progenitor populations which are collectively grouped into MSCs (mesenchymal stem cells). Such cells have been sourced from each component of the cord, namely the subamnion layer, the WJ, the perivascular region, and the vessels. These cells mainly show adherence to the phenotype of adult MSCs (as bone marrow-derived ones) and can differentiate towards mature cell types belonging to all the three germ layers. In addition, cells from human UC are derived from an immunoprivileged organ, namely the placenta: in fact, its development and function depend on the elusion of the maternal immune response towards the semi-allogeneic embryo. This is reflected in the expression of immunomodulatory molecules by UC-derived MSCs. The present paper describes UC structural features and the cell types which can be derived, with a focus on their phenotype and the novel results which boosted the use of UC-derived cells for regenerative medicine applications.
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    Visual deficits after traumatic brain injury
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Rasiah, Pratheepa Kumari; Geier, Ben; Jha, Kumar Abhiram; Gangaraju, Rajashekhar
    Traumatic brain injury (TBI) is frequently described as any head injury ceasing the brain's normal function. Anatomically, developmentally, and physiologically, the eye is deemed as an extension of the brain. Vision in TBI is underrepresented, and the number of active clinical trials in this field are sparse. Frequently, visual problems are overlooked at the time of TBI, often resulting in progressive vision loss, lengthening, and impairing rehabilitation. TBI can be either penetrative or non-penetrative, associated with degeneration of neurons, apoptotic cell death, inflammation, microglial activation, hemorrhage associated with vascular dysfunction; however, precise animal modeling that mimics the extensive visual deficits of TBI pathology remain elusive. Recent works in both the diagnostics and therapeutics fields are starting to make substantial progress in the right direction. Discussion of current advancements in TBI animal models and the recent pathophysiological findings related to the neuro-glia-vascular unit (NVU) will help elucidate novel targets for potential lines of therapeutics. Only over the past decade have newer pharmaceutical and stem cell-based treatments begun to come to light. The potency for these new lines of TBI specific curatives will be discussed along with the review of current blast-induced TBI models, providing potential directions for future research.