scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

Psychiatric neurosurgery

2018 ◽  
pp. 135-184
Author(s):  
Walter Glannon
Keyword(s):  
Clinical Trials ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Neural Circuits ◽  
Therapeutic Potential ◽  
Genetic Material ◽  
Research Subjects ◽  
Ethical Justification ◽  
The Brain ◽  
Deep Brain

This chapter discusses functional neurosurgery designed to modulate dysfunctional neural circuits mediating sensorimotor, cognitive, emotional, and volitional capacities. The chapter assesses the comparative benefits and risks of neural ablation and deep brain stimulation as the two most invasive forms of neuromodulation. It discusses the question of whether individuals with a severe or moderately severe psychiatric disorder have enough cognitive and emotional capacity to weigh reasons for and against ablation or deep brain stimulation and give informed consent to undergo it. The chapter also discusses the obligations of investigators conducting these trials to research subjects. In addition, it examines the medical and ethical justification for a sham control arm in psychiatric neurosurgery clinical trials. It considers the therapeutic potential of optogenetics as a novel form of neuromodulation. The fact that this technique manipulates both genetic material and neural circuits and has been tested only in animal models makes it unclear what its benefit–risk ratio would be. The chapter concludes with a brief discussion of the potential of neuromodulation to stimulate endogenous repair and growth mechanisms in the brain.

scholarly journals Stem Cell-Derived Extracellular Vesicles and Kidney Regeneration

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1240 ◽  
Author(s):  
Grange ◽  
Skovronova ◽  
Marabese ◽  
Bussolati
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Therapeutic Option ◽  
Genetic Material ◽  
Kidney Injury ◽  
Convincing Evidence ◽  
Apoptosis And Inflammation ◽  
Injury Models ◽  
New Strategies

Extracellular vesicles (EVs) are membranous vesicles containing active proteins, lipids, and different types of genetic material such as miRNAs, mRNAs, and DNAs related to the characteristics of the originating cell. They possess a distinctive capacity to communicate over long distances. EVs have been involved in the modulation of several pathophysiological conditions and, more importantly, stem cell-derived EVs appear as a new promising therapeutic option. In fact, several reports provide convincing evidence of the regenerative potential of EVs released by stem cells and, in particular, mesenchymal stromal cells (MSCs) in different kidney injury models. Described mechanisms involve the reprogramming of injured cells, cell proliferation and angiogenesis, and inhibition of cell apoptosis and inflammation. Besides, the therapeutic use of MSC-EVs in clinical trials is under investigation. This review will focus on MSC-EV applications in preclinical models of acute and chronic renal damage including recent data on their use in kidney transplant conditioning. Moreover, ongoing clinical trials are described. Finally, new strategies to broaden and enhance EV therapeutic efficacy by engineering are discussed.

scholarly journals Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late

2018 ◽  
Vol 19 (8) ◽  
pp. 2380 ◽  
Author(s):  
Michiel Remmerie ◽  
Veerle Janssens
Keyword(s):  
Clinical Trials ◽  
Endometrial Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Genetic Alterations ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Type Ii

Type II endometrial carcinomas (ECs) are responsible for most endometrial cancer-related deaths due to their aggressive nature, late stage detection and high tolerance for standard therapies. However, there are no targeted therapies for type II ECs, and they are still treated the same way as the clinically indolent and easily treatable type I ECs. Therefore, type II ECs are in need of new treatment options. More recently, molecular analysis of endometrial cancer revealed phosphorylation-dependent oncogenic signalling in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways to be most frequently altered in type II ECs. Consequently, clinical trials tested pharmacologic kinase inhibitors targeting these pathways, although mostly with rather disappointing results. In this review, we highlight the most common genetic alterations in type II ECs. Additionally, we reason why most clinical trials for ECs using targeted kinase inhibitors had unsatisfying results and what should be changed in future clinical trial setups. Furthermore, we argue that, besides kinases, phosphatases should no longer be ignored in clinical trials, particularly in type II ECs, where the tumour suppressive phosphatase protein phosphatase type 2A (PP2A) is frequently mutated. Lastly, we discuss the therapeutic potential of targeting PP2A for (re)activation, possibly in combination with pharmacologic kinase inhibitors.

AR amplification eradication with high-dose testosterone (T) in patients with heavily pretreated mCRPC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 251-251
Author(s):  
Patrick Cotogno ◽  
Elisa M. Ledet ◽  
Joshua Schiff ◽  
Charlotte Manogue ◽  
Brian E. Lewis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Reports ◽  
Therapeutic Option ◽  
Treatment Options ◽  
P53 Mutation ◽  
Cancer Center ◽  
High Dose ◽  
Circulating Free Dna ◽  
Radium 223 ◽  
Heavily Pretreated

251 Background: Patients (Pts) with mCRPC resistant to novel hormones (abi/enza) and taxanes pose a challenge for clinicians. Typically, once these agents are exhausted, clinical trials represent the best therapeutic option; however, many pts are not appropriate for clinical trials due to marrow suppression and/or extensive pre-treatments. Herein we present limited experience with three pts treated with high dose T when therapeutic clinical trial options were not available. Methods: Data was retrospectively collected at Tulane Cancer Center for pt treatment history, laboratory parameters, and circulating free-DNA genomic testing. High dose testosterone was used at a dose of 87.5-100 mg given daily as a 1% testosterone gel applied to the skin. Results: All the mCRPC patients were pre-treated with abi, enza, taxanes, & radium-223. All pts had RBC transfusions due to marrow suppression. All patients were previously treated on clinical trials. After starting high dose T, pt 1 demonstrated a clinical improvement in energy and appetite with a PSA decline from 530 to 45.8 ng/ml (-91.4%) over 30 days. At baseline, cfDNA analyses measured 15.9X AR amplification and 3.7X MYC amplification. The cfDNA also contained 9.8% of P53R273H mutation. Post high-dose T (serum T from castrate to 1462 ng/dL), both of the cfDNA measured amplifications returned to normal and P53 mutation declined to 0.5%. The PSA nadir occurred 30 days after T start; T was stopped 96 days after starting because of PSA rise to 280 ng/ml. The pt then restarted abi, despite prior resistance, and PSA declined from 280 to 65 ng/ml (-76.6%). The 2 other patients had PSA increases and clinical deterioration and high dose T was stopped after 2-3 weeks. Conclusions: Response to high dose T has been reported in occasional case reports going back over 60 years ago (see Brendler H et al. Arch Surg 1950;61:433–40). The frequency of favorable responses is unknown. In one case, a reversal of AR and MYC amplification was observed. The responding patient then was re-sensitized to abi, a drug to which he was previously resistant. Further research, such as the TRANSFORMER trial, is needed to understand the molecular changes and treatment options for this population.

scholarly journals The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors

2021 ◽  
Vol 22 (21) ◽  
pp. 11385
Author(s):  
Rodion A. Velichinskii ◽  
Maria A. Streltsova ◽  
Sofya A. Kust ◽  
Alexander M. Sapozhnikov ◽  
Elena I. Kovalenko
Keyword(s):  
Clinical Trials ◽  
Nk Cells ◽  
Solid Tumors ◽  
Nk Cell ◽  
Therapeutic Potential ◽  
Cell Based Therapy ◽  
Tumor Environment ◽  
Low Efficiency ◽  
Alternative Sources ◽  
Hematological Tumors

NK cells are an attractive target for cancer immunotherapy due to their potent antitumor activity. The main advantage of using NK cells as cytotoxic effectors over T cells is a reduced risk of graft versus host disease. At present, several variants of NK-cell-based therapies are undergoing clinical trials and show considerable effectiveness for hematological tumors. In these types of cancers, the immune cells themselves often undergo malignant transformation, which determines the features of the disease. In contrast, the current use of NK cells as therapeutic agents for the treatment of solid tumors is much less promising. Most studies are at the stage of preclinical investigation, but few progress to clinical trials. Low efficiency of NK cell migration and functional activity in the tumor environment are currently considered the major barriers to NK cell anti-tumor therapies. Various therapeutic combinations, genetic engineering methods, alternative sources for obtaining NK cells, and other techniques are aiming at the development of promising NK cell anticancer therapies, regardless of tumorigenesis. In this review, we compare the role of NK cells in the pathogenesis of hematological and solid tumors and discuss current prospects of NK-cell-based therapy for hematological and solid tumors.

scholarly journals Afatinib restrains K-RAS–driven lung tumorigenesis

2018 ◽  
Vol 10 (446) ◽  
pp. eaao2301 ◽  
Author(s):  
Herwig P. Moll ◽  
Klemens Pranz ◽  
Monica Musteanu ◽  
Beatrice Grabner ◽  
Natascha Hruschka ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mouse Models ◽  
First Generation ◽  
Therapeutic Potential ◽  
Experimental Models ◽  
Genetically Engineered ◽  
Tumor Escape ◽  
Lung Tumorigenesis ◽  
Egfr Inhibition

On the basis of clinical trials using first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), it became a doctrine that V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) mutations drive resistance to EGFR inhibition in non–small cell lung cancer (NSCLC). Conversely, we provide evidence that EGFR signaling is engaged in K-RAS–driven lung tumorigenesis in humans and in mice. Specifically, genetic mouse models revealed that deletion of Egfr quenches mutant K-RAS activity and transiently reduces tumor growth. However, EGFR inhibition initiates a rapid resistance mechanism involving non-EGFR ERBB family members. This tumor escape mechanism clarifies the disappointing outcome of first-generation TKIs and suggests high therapeutic potential of pan-ERBB inhibitors. On the basis of various experimental models including genetically engineered mouse models, patient-derived and cell line–derived xenografts, and in vitro experiments, we demonstrate that the U.S. Food and Drug Administration–approved pan-ERBB inhibitor afatinib effectively impairs K-RAS–driven lung tumorigenesis. Our data support reconsidering the use of pan-ERBB inhibition in clinical trials to treat K-RAS–mutated NSCLC.

scholarly journals Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 9 (11) ◽  
pp. 3507
Author(s):  
Erika Grossrubatscher ◽  
Giuseppe Fanciulli ◽  
Luca Pes ◽  
Franz Sesti ◽  
Carlotta Dolci ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Radionuclide Therapy ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Medullary Thyroid ◽  
Peptide Receptor

Effective treatment options in advanced/progressive/metastatic medullary thyroid carcinoma (MTC) are currently limited. As in other neuroendocrine neoplasms (NENs), peptide receptor radionuclide therapy (PRRT) has been used as a therapeutic option in MTC. To date, however, there are no published reviews dealing with PRRT approaches. We performed an in-depth narrative review on the studies published in this field and collected information on registered clinical trials related to this topic. We identified 19 published studies, collectively involving more than 200 patients with MTC, and four registered clinical trials. Most cases of MTC were treated with PRRT with somatostatin analogues (SSAs) radiolabelled with 90 yttrium (90Y) and 177 lutetium (177Lu). These radiopharmaceuticals show efficacy in the treatment of patients with MTC, with a favourable radiological response (stable disease, partial response or complete response) in more than 60% of cases, coupled with low toxicity. As MTC specifically also expresses cholecystokinin receptors (CCK2Rs), PRRT with this target has also been tried, and some randomised trials are ongoing. Overall, PRRT seems to have an effective role and might be considered in the therapeutic strategy of advanced/progressive/metastatic MTC.

scholarly journals Detection and Monitoring of Regulatory Immune Cells Following Their Adoptive Transfer in Organ Transplantation

2020 ◽  
Vol 11 ◽  
Author(s):  
Lillian M. Tran ◽  
Angus W. Thomson
Keyword(s):  
Clinical Trials ◽  
Organ Transplantation ◽  
Immune Cells ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Tolerance Induction ◽  
Current Status ◽  
Transplant Tolerance ◽  
Cell Based Therapy

Application of cell-based immunotherapy in organ transplantation to minimize the burden of immunosuppressive medication and promote allograft tolerance has expanded significantly over the past decade. Adoptively transferred regulatory immune cells prolong allograft survival and transplant tolerance in pre-clinical models. Many cell products are currently under investigation in early phase human clinical trials designed to assess feasibility and safety. Despite rapid advances in manufacturing practices, defining the appropriate protocol that will optimize in vivo conditions for tolerance induction remains a major challenge and depends heavily on understanding the fate, biodistribution, functional stability and longevity of the cell product after administration. This review focuses on in vivo detection and monitoring of various regulatory immune cell types administered for allograft tolerance induction in both pre-clinical animal models and early human clinical trials. We discuss the current status of various non-invasive methods for tracking regulatory cell products in the context of organ transplantation and implications for enhanced understanding of the therapeutic potential of cell-based therapy in the broad context of control of immune-mediated inflammatory disorders.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 588
Author(s):  
Vladimir Holan ◽  
Katerina Palacka ◽  
Barbora Hermankova
Keyword(s):  
Clinical Trials ◽  
Experimental Studies ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

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