scholarly journals Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Izabela Malysz-Cymborska ◽  
Dominika Golubczyk ◽  
Lukasz Kalkowski ◽  
Joanna Kwiatkowska ◽  
Michal Zawadzki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
Neurological Diseases ◽  
Inflammatory Factors ◽  
Treatment Control ◽  
Broad Distribution ◽  
Pre Treatment ◽  
Large Animals ◽  
The Brain

AbstractStem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Canine GRP transplantation in dogs resulted in rather poor retention in the brain, so MSCs were used in subsequent experiments. To evaluate the safety of MSC intraarterial transplantation, naïve pigs (n = 3) were used as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. The procedure in pigs has proven to be safe and histopathology has demonstrated the successful and predictable placement of transplanted porcine MSCs. Transplantation of canine MSCs in DM dogs resulted in their accumulation in the brain. Interventional and follow-up MRI proved the procedure was feasible and safe. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.

scholarly journals Intra-Arterial Transplantation of Stem Cells in Large Animals – A Minimally-Invasive Strategy for the Treatment of Disseminated Neurodegeneration

2020 ◽  
Author(s):  
Izabela Malysz-Cymborska ◽  
Dominika Golubczyk ◽  
Lukasz Kalkowski ◽  
Joanna Kwiatkowska ◽  
Michal Zawadzki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
Neurological Diseases ◽  
Inflammatory Factors ◽  
Treatment Control ◽  
Broad Distribution ◽  
Pre Treatment ◽  
Large Animals ◽  
The Brain

Abstract Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Three naïve pigs were used for MSC transplantation as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. Interventional and follow-up MRI proved the procedure was feasible and safe. The transplantation of canine GRPs resulted in rather poor retention in the brain, whereas canine MSCs demonstrated excellent settlement. Notably, histopathology showed the successful and predictable placement of transplanted porcine MSCs. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.

scholarly journals Strategies to Improve the Quality and Freshness of Human Bone Marrow-Derived Mesenchymal Stem Cells for Neurological Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Da Yeon Lee ◽  
Sung Eun Lee ◽  
Do Hyeon Kwon ◽  
Saraswathy Nithiyanandam ◽  
Mi Ha Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Neurological Diseases ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Culture Dish ◽  
Cell Based Therapy ◽  
The Brain

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been studied for their application to manage various neurological diseases, owing to their anti-inflammatory, immunomodulatory, paracrine, and antiapoptotic ability, as well as their homing capacity to specific regions of brain injury. Among mesenchymal stem cells, such as BM-MSCs, adipose-derived MSCs, and umbilical cord MSCs, BM-MSCs have many merits as cell therapeutic agents based on their widespread availability and relatively easy attainability and in vitro handling. For stem cell-based therapy with BM-MSCs, it is essential to perform ex vivo expansion as low numbers of MSCs are obtained in bone marrow aspirates. Depending on timing, before hBM-MSC transplantation into patients, after detaching them from the culture dish, cell viability, deformability, cell size, and membrane fluidity are decreased, whereas reactive oxygen species generation, lipid peroxidation, and cytosolic vacuoles are increased. Thus, the quality and freshness of hBM-MSCs decrease over time after detachment from the culture dish. Especially, for neurological disease cell therapy, the deformability of BM-MSCs is particularly important in the brain for the development of microvessels. As studies on the traditional characteristics of hBM-MSCs before transplantation into the brain are very limited, omics and machine learning approaches are needed to evaluate cell conditions with indepth and comprehensive analyses. Here, we provide an overview of hBM-MSCs, the application of these cells to various neurological diseases, and improvements in their quality and freshness based on integrated omics after detachment from the culture dish for successful cell therapy.

scholarly journals From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier?

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Linan Liu ◽  
Mark A. Eckert ◽  
Hamidreza Riazifar ◽  
Dong-Ku Kang ◽  
Dritan Agalliu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Blood Brain ◽  
The Brain

Systemically infused mesenchymal stem cells (MSCs) are emerging therapeutics for treating stroke, acute injuries, and inflammatory diseases of the central nervous system (CNS), as well as brain tumors due to their regenerative capacity and ability to secrete trophic, immune modulatory, or other engineered therapeutic factors. It is hypothesized that transplanted MSCs home to and engraft at ischemic and injured sites in the brain in order to exert their therapeutic effects. However, whether MSCs possess the ability to migrate across the blood-brain barrier (BBB) that separates the blood from the brain remains unresolved. This review analyzes recent advances in this area in an attempt to elucidate whether systemically infused MSCs are able to actively transmigrate across the CNS endothelium, particularly under conditions of injury or stroke. Understanding the fate of transplanted MSCs and their CNS trafficking mechanisms will facilitate the development of more effective stem-cell-based therapeutics and drug delivery systems to treat neurological diseases and brain tumors.

Rupture of lenticulostriate artery aneurysms

2014 ◽  
Vol 120 (2) ◽  
pp. 426-433 ◽  
Author(s):  
Olivier Heck ◽  
René Anxionnat ◽  
Jean-Christophe Lacour ◽  
Anne-Laure Derelle ◽  
Xavier Ducrocq ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
First Line ◽  
Ischemic Event ◽  
Bilateral Case ◽  
History Of ◽  
Lenticulostriate Artery ◽  
The Right ◽  
The Brain ◽  
Deep Location

The authors report on 3 rare cases of ruptured lenticulostriate artery (LSA) aneurysms that were heralded by deep cerebral hematomas. The hematomas were unilateral in 2 cases and bilateral in 1; in the bilateral case, only a single LSA aneurysm could be identified on the right side of the brain. Because of their small size (≤ 2 mm), fusiform aspect, and deep location within the brain, all of the aneurysms were treated conservatively. There was no hemorrhage recurrence, and follow-up angiography demonstrated spontaneous thrombosis in 2 of the 3 cases. The clinical course was favorable in 2 of the 3 patients. The course in the patient with the bilateral hematoma was marked by an ischemic event after the initial episode, resulting in an aggravation of deficits. The cause of this second event was uncertain. Because our knowledge about the natural history of LSA aneurysms is incomplete, there is no consensus concerning a therapeutic strategy. The authors' experience in 3 reported cases leads them to think that a conservative approach involving close angiographic monitoring may be proposed as first-line treatment. If the monitored aneurysm then persists or grows in size, its occlusion should be considered. Nonetheless, other studies are needed to further strengthen the legitimacy of this strategy.

Autophagy & phagocytosis in neurological disorders and their possible cross-talk

2021 ◽  
Vol 19 ◽  
Author(s):  
Gaigai Li ◽  
Prativa Sherchan ◽  
Zhouping Tang ◽  
Jiping Tang
Keyword(s):  
Brain Injury ◽  
Cross Talk ◽  
Neurological Disorders ◽  
Therapeutic Strategy ◽  
Neurological Diseases ◽  
Phagocytic Process ◽  
The Future ◽  
The Brain

: Autophagy and phagocytosis are two important endogenous lysosomal dependent clearing systems in the organism. In some neurological disorders, excessive autophagy or dysfunctional phagocytosis have been shown to contribute to brain injury. Recent studies have revealed that there are underlying interactions between these two processes. However, different studies show inconsistent results for the contribution of autophagy to the phagocytic process in diverse phagocytes and relatively little is known about the link between them especially in the brain. It is critical to understand the role that autophagy plays in phagocytic process in order to promote clearance of endogenous and exogenous detrimental materials. In this review, we highlight studies that focused on phagocytosis and autophagy occurring in the brain and summarized the possible regulatory roles of autophagy in the process of phagocytosis. Balancing the roles of autophagy and phagocytosis may be a promising therapeutic strategy for the treatment of some neurological diseases in the future.

scholarly journals Potential of Neural Stem Cells for the Treatment of Brain Tumors

2008 ◽  
Vol 2 ◽  
pp. CMO.S747
Author(s):  
P. Taupin
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cellular Therapy ◽  
Neurological Diseases ◽  
Neural Progenitor ◽  
Multipotent Cells ◽  
The Brain ◽  
Combine Gene ◽  
Potential Use

Neural stem cells (NSCs) are self-renewing multipotent cells that generate the main phenotypes of the nervous system, neurons, astrocytes and oligodendrocytes. As such they hold the promise to treat a broad range of neurological diseases and injuries. Neural progenitor and stem cells have been isolated and characterized in vitro, from adult, fetal and post-mortem tissues, providing sources of material for cellular therapy. However, NSCs are still elusive cells and remain to be unequivocally identified and characterized, limiting their potential use for therapy. Neural progenitor and stem cells, isolated and cultured in vitro, can be genetically modified and when transplanted migrate to tumor sites in the brain. These intrinsic properties of neural progenitor and stem cells provide tremendous potential to bolster the translation of NSC research to therapy. It is proposed to combine gene therapy and cellular therapy to treat brain cancers. Hence, neural progenitor and stem cells provide new opportunities for the treatment of brain cancers.

scholarly journals Added-Value of Endometrial Biopsy in the Diagnostic and Therapeutic Strategy for Pelvic Actinomycosis

2020 ◽  
Vol 9 (3) ◽  
pp. 821
Author(s):  
Julie Carrara ◽  
Blandine Hervy ◽  
Yohann Dabi ◽  
Claire Illac ◽  
Bassam Haddad ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Therapeutic Strategy ◽  
Endometrial Biopsy ◽  
Diagnostic Methods ◽  
Added Value ◽  
Diagnostic Tools ◽  
Histopathological Analysis ◽  
Pelvic Actinomycosis ◽  
Pre Treatment

The particularity of pelvic actinomycosis lies in the difficulty of establishing the diagnosis prior to treatment. The objective of this retrospective bicentric study was to evaluate the pertinence and efficacy of the different diagnostic tools used pre- and post-treatment in a cohort of patients with pelvic actinomycosis. The following data were collected: clinical, paraclinical, type of treatment, and the outcome and pertinence of the two diagnostic methods, bacteriological or histopathological, were evaluated. Twenty-seven women were included, with a pre-treatment diagnosis proposed for 66.7% (n = 18) of them. The diagnosis was established in 13.6% (n = 3) of cases through bacteriological samples, and in 93.8% (n = 15) of cases through histopathological samples, with endometrial biopsy positive in 100% of cases. The treatment was surgical with antibiotics for 55.6% (n = 15) of patients, medical with antibiotic therapy for 40.7% (n = 11) of patients, and surgical without antibiotics for one patient. All patients achieved recovery without recurrence, with a median follow-up of 96 days (4–4339 days). Our study suggested an excellent performance of histopathological analysis, and in particular endometrial biopsy, in the diagnosis of pelvic actinomycosis. This tool allowed early diagnosis and, in some cases, the use of antibiotic therapy alone, making it possible to avoid surgery.

scholarly journals Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium

2017 ◽  
Vol 45 (5) ◽  
pp. 1151-1161 ◽  
Author(s):  
Maarten J.C. Leijs ◽  
Gerben M. van Buul ◽  
Jan A.N. Verhaar ◽  
Martin J. Hoogduijn ◽  
Pieter K. Bos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Calf Serum ◽  
Inflammatory Factors ◽  
Adhesion Receptors ◽  
Osteoarthritic Cartilage ◽  
Cell Based Therapy ◽  
Pre Treatment

Background: Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. Hypothesis: Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. Study Design: Controlled laboratory study. Methods: We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. Results: Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. Conclusion: Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. Clinical Relevance: To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.

scholarly journals Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
N. K. Venkataramana ◽  
Rakhi Pal ◽  
Shailesh A. V. Rao ◽  
Arun L. Naik ◽  
Majahar Jan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Subventricular Zone ◽  
Early Stage ◽  
Clinical Status ◽  
Pilot Clinical Study ◽  
The Brain

The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during “on” and 31.21% during “off” period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years) showed more improvement and no further disease progression than the later stages (11–15 years). However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

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