scholarly journals Cell-free Fat Extract Promote Axon Regeneration: a Pre-clinical Study.

2021 ◽  
Author(s):  
Yiyu Sun ◽  
Xiangsheng Wang ◽  
Di Chen ◽  
Ziyou Yu ◽  
Wenjie Zhang
Keyword(s):  
Stem Cell ◽  
Optic Nerve ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Axon Regeneration ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regeneration Ability ◽  
Therapeutic Effects ◽  
Go Annotation

Abstract Background: Injured axons of the central nervous system (CNS) hardly regenerate due to their poor intrinsic regeneration ability and adverse microenvironment at the site of injury; previous studies aimed to investigate both the above-mentioned factors and achieved some success. Compared with the gene-editing technology, stem cell therapy has unique advantages, such as low risk of tumor formation and ease-of-use, among others. However, traditional stem cell therapy is hindered by safety and immunogenicity issues. Previously, we developed a cell-free extract directly from human fat tissue (CEFFE) and demonstrated its proangiogenic capacity. Herein, we aimed to evaluate its potential therapeutic effect in injured CNS.Methods: Therapeutic potential of CEFFE in injured CNS was investigated, using a mouse optic nerve crush model. After the optic nerve was crushed, CEFFE was injected intravitreally. Two weeks post-injury, the number of regenerated axons was measured at different distances from the crush site (250, 500, 750, 1000, and 1500 µm). In addition, surviving retinal ganglion cells (RGCs) were counted. Cellular locations and catalogs of CEFFE were analyzed by gene ontology (GO) annotation. Western blotting (WB) was performed to evaluate the therapeutic effects of CEFFE on the molecular level. An enzyme-linked immunosorbent assay (ELISA) was used to examine the levels of inflammatory factors in CEFFE. Results: Compared with brain-derived neurotrophic factor (BDNF), CEFFE effectively promoted axon regeneration and RGCs survival. GO annotation showed that 146 proteins were involved in axon genesis or neurogenesis, most of which were located intracellularly. WB and ELISA results showed that CEFFE acted on diverse pathways and involved high levels of inflammatory factors. Conclusions: The present findings have shown that CEFFE may promote axon regeneration and increase RGCs survival. The levels of factors involved in CEFFE were much higher than those observed in the traditional secretome; CEFFE involves multiple factors and affects several mechanisms. This study has revealeded the potential application of CEFFE for the treatment of CNS injury.

scholarly journals Therapeutic effect and safety of stem cell therapy for chronic liver disease: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guang-Peng Zhou ◽  
Yi-Zhou Jiang ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu
Keyword(s):  
Stem Cell ◽  
Liver Disease ◽  
Adverse Events ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Meta Analysis ◽  
Chronic Liver ◽  
Controlled Trials ◽  
Therapeutic Effects ◽  
Term Survival

Abstract Background Stem cell therapy is becoming an emerging therapeutic option for chronic liver disease (CLD). However, whether stem cell therapy is more effective than conventional treatment remains questionable. We performed a large-scale meta-analysis of randomized controlled trials (RCTs) to evaluate the therapeutic effects and safety of stem cell therapy for CLD. Methods We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases for the period from inception through March 16, 2020. Primary outcomes were all-cause mortality and adverse events related to stem cell therapy. Secondary outcomes included the model for end-stage liver disease score, total bilirubin, albumin, alanine aminotransferase, prothrombin activity, and international normalized ratio. The standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model. Results Twenty-four RCTs were included and the majority of these studies showed a high risk of bias. The meta-analysis indicated that compared with conventional treatment, stem cell therapy was associated with improved survival and liver function including the model of end-stage liver disease score, total bilirubin, and albumin levels. However, it had no obvious beneficial effects on alanine aminotransferase level, prothrombin activity, and international normalized ratio. Subgroup analyses showed stem cell therapy conferred a short-term survival benefit for patients with acute-on-chronic liver failure (ACLF), a single injection was more effective than multiple injections, hepatic arterial infusion was more effective than intravenous infusion, and bone marrow-derived stem cells were more effective than those derived from the umbilical cord. Thirteen trials reported adverse events related to stem cell therapy, but no serious adverse events were reported. Conclusions Stem cell therapy is a safe and effective therapeutic option for CLD, while patients with ACLF benefit the most in terms of improved short-term survival. A single injection administration of bone marrow-derived stem cells via the hepatic artery has superior therapeutic effects.

scholarly journals A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p–PIK3R1 axis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Mingyang Li ◽  
Rong Cong ◽  
Liyu Yang ◽  
Lei Yang ◽  
Yiqi Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Tissue Regeneration ◽  
Stem Cell Therapy ◽  
Therapeutic Effects ◽  
The Novel ◽  
Akt Signaling Pathway ◽  
Physiological Conditions ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Bone marrow-derived mesenchymal stem cells (BMSCs) in postmenopausal osteoporosis models exhibit loss of viability and multipotency. Identification of the differentially expressed RNAs in osteoporotic BMSCs could reveal the mechanisms underlying BMSC dysfunction under physiological conditions, which might improve stem cell therapy and tissue regeneration. In this study, we performed high-throughput RNA sequencing and showed that the novel long non-coding RNA (lncRNA) LNC_000052 and its co-expressed mRNA PIK3R1 were upregulated in osteoporotic BMSCs. Knockdown of LNC_000052 could promote BMSC proliferation, migration, osteogenesis, and inhibit apoptosis via the PI3K/Akt signaling pathway. We found that both LNC_000052 and PIK3R1 shared a miRNA target, miR-96-5p, which was downregulated in osteoporotic BMSCs. Their binding sites were confirmed by dual-luciferase assays. Downregulation of miR-96-5p could restrain the effects of LNC_000052 knockdown while upregulation of miR-96-5p together with LNC_000052 knockdown could improve the therapeutic effects of BMSCs. In summary, the LNC_000052–miR-96-5p–PIK3R1 axis led to dysfunction of osteoporotic BMSCs and might be a novel therapeutic target for stem cell therapy and tissue regeneration.

scholarly journals Regenerative Cardiovascular Therapies: Stem Cells and Beyond

2019 ◽  
Vol 20 (6) ◽  
pp. 1420 ◽  
Author(s):  
Bernhard Wernly ◽  
Moritz Mirna ◽  
Richard Rezar ◽  
Christine Prodinger ◽  
Christian Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Basic Science ◽  
Left Ventricular ◽  
Specific Cell ◽  
Therapeutic Effects ◽  
Cell Processing

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.

scholarly journals Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Zhang ◽  
Xin-xing Wan ◽  
Xi-min Hu ◽  
Wen-juan Zhao ◽  
Xiao-xia Ban ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Programmed Cell Death ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Effects ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Wide Range

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.

scholarly journals Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: A comprehensive review

2021 ◽  
Author(s):  
Alireza Ebrahimi ◽  
Hanie Ahmadi ◽  
Zahra Pourfraidon Ghasrodashti ◽  
Nader Tanide ◽  
Reza Shahriarirad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Musculoskeletal Diseases ◽  
Large Population ◽  
Therapeutic Effects ◽  
Full Potential ◽  
Differentiation Process ◽  
Organ Systems

Stem cell therapy has been used to treat several types of diseases, and it is expected that its therapeutic uses shall increase as novel lines of evidence begin to appear. Furthermore, stem cells have the potential to make new tissues and organs. Thus, some scientists propose that organ transplantation will significantly rely on stem cell technology and organogenesis in the future. Stem cells and its robust potential to differentiate into specific types of cells and regenerate tissues and body organs, have been investigated by numerous clinician scientists and researchers for their therapeutic effects. Degenerative diseases in different organs have been the main target of stem cell therapy. Neurodegenerative diseases such as Alzheimer's, musculoskeletal diseases such as osteoarthritis, congenital cardiovascular diseases, and blood cell diseases such as leukemia are among the health conditions that have benefited from stem cell therapy advancements. One of the most challenging parts of the process of incorporating stem cells into clinical practice is controlling their division and differentiation potentials. Sometimes, their potential for  uncontrolled growth will make these cells tumorigenic. Another caveat in this process is the ability to control the differentiation process. While stem cells can easily differentiate into a wide variety of cells,  a paracrine effect controlled activity, being in an appropriate medium will cause abnormal differentiation leading to treatment failure. In this review, we aim to provide an overview of the therapeutic effects of stem cells in diseases of various organ systems. In order to advance this new treatment to its full potential, researchers should focus on establishing methods to control the differentiation process, while policymakers should take an active role in providing adequate facilities and equipment for these projects. Large population clinical trials are a necessary tool that will help build trust in this method. Moreover, improving social awareness about the advantages and adverse effects of stem cell therapy is required to develop a rational demand in the society, and consequently, healthcare systems should consider established stem cell-based therapeutic methods in their treatment algorithms.  

scholarly journals Mechanism and Prevention of Spiral Ganglion Neuron Degeneration in the Cochlea

2022 ◽  
Vol 15 ◽  
Author(s):  
Li Zhang ◽  
Sen Chen ◽  
Yu Sun
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Stem Cell ◽  
Cell Therapy ◽  
Sensory Neurons ◽  
Stem Cell Therapy ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neuron ◽  
Regeneration Ability ◽  
Ganglion Neurons

Sensorineural hearing loss (SNHL) is one of the most prevalent sensory deficits in humans, and approximately 360 million people worldwide are affected. The current treatment option for severe to profound hearing loss is cochlear implantation (CI), but its treatment efficacy is related to the survival of spiral ganglion neurons (SGNs). SGNs are the primary sensory neurons, transmitting complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus. In mammals, SGNs have very limited regeneration ability, and SGN loss causes irreversible hearing loss. In most cases of SNHL, SGN damage is the dominant pathogenesis, and it could be caused by noise exposure, ototoxic drugs, hereditary defects, presbycusis, etc. Tremendous efforts have been made to identify novel treatments to prevent or reverse the damage to SGNs, including gene therapy and stem cell therapy. This review summarizes the major causes and the corresponding mechanisms of SGN loss and the current protection strategies, especially gene therapy and stem cell therapy, to promote the development of new therapeutic methods.

scholarly journals Comparison of the therapeutic effect of BMSCs and culture supernatant injection therapy on osteoarthritis and mechanism exploration

2020 ◽  
Author(s):  
Yiqi Peng ◽  
Rui Zhao ◽  
Sheng Huang ◽  
Shilin Xiong ◽  
Qitao Yan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Articular Cartilage ◽  
Cell Therapy ◽  
Therapeutic Effect ◽  
Culture System ◽  
Culture Supernatant ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Injection Treatment

Abstract Background Osteoarthritis (OA) is a chronic disease that can cause disability. The prevalence of osteoarthritis has increased year by year, become a disease that mainly causes the elderly to suffer. With the increasing understanding of bone marrow mesenchymal stem cell (BMSC) in tissue repair, BMSCs shown good therapeutic effects in OA, it may be due to BMSCs exerted their capacities of differentiation, secretion and immunoregulatory in the joints. As previous describe, BMSCs culture supernatant is proved that rich in multiple cytokines. Therefore, how BMSCs injection therapy exerts its ability to exert therapeutic effects, and whether its therapeutic effect can be replaced by its culture supernatant has become the focus of this article. Methods In vitro, we designed a co-culture system to deepen understand this new stem cell therapy. Through two kinds of cells cultured alone, direct and indirect cell contact co-culture to observe changes in cell morphology, quantity and cytoplasmic glycoprotein of these two types of cells and changes of the level of growth factor in the culture supernatant to explore the interaction of these two types of cells; in vivo, we induced an OA model and Injected Saline solution, BMSCs and their culture supernatants respectively for treatment, then we compared the improvement results of OA by evaluating changes in the cartilage layer after different treatments. And determine the changes of some growth factors and inflammatory factors in synovial fluid to analyze the possible mechanisms of multiple treatments. Result In the co-culture system, it was found that the direct co-culture of BMSCs and OCs can enhance the proliferation ability of OCs, OCs can retain more cytoplasmic glycoprotein, and BMSCs did not occurred abnormal differentiation during the co-culture. In animal experiments, it was found that the ability of BMSCs injection treatment has obvious therapeutic effect on OA, and the effect is better than its supernatant injection treatment. BMSCs therapy reduced matrix loss in articular cartilage cells, and reduced type I collagen production and fibrosis on articular cartilage, effectively regulating EGF and TGF-β1change and inhibited intra-articular inflammation. Supernatant injection treatment will not significantly delay the progress of OA, and it cannot replace BMSCs for the treatment of OA. Conclusion BMSCs therapy is a potential new therapy for OA. The secretion and regulation ability of BMSCs plays an important role in the treatment process. BMSCs are activated by the intra-articular environment of OA, regulating growth factors such as EGF and TGFβ to promote articular cartilage regeneration, and reducing intra-articular inflammation by regulating inflammatory factors and delaying the progression of OA. These effects cannot be replaced by the culture supernatant which is rich in multiple factors, and its regulation function requires the presence of BMSCs. These results provide a relatively comprehensive understanding of BMSCs cell therapy in OA and provide a new explanation for the possible anti-inflammatory effects of BMSCs in the joint.

scholarly journals From Mesenchymal Stromal Cells to Engineered Extracellular Vesicles: A New Therapeutic Paradigm

2021 ◽  
Vol 9 ◽  
Author(s):  
Jancy Johnson ◽  
Mozhgan Shojaee ◽  
James Mitchell Crow ◽  
Ramin Khanabdali
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stem Cell Therapy ◽  
Stromal Cells ◽  
Therapeutic Effects ◽  
Paracrine Factor ◽  
Cell Source ◽  
Therapeutic Development

Mesenchymal stromal cells (MSCs) are multipotent cells obtained from many tissues including bone marrow, adipose tissue, umbilical cord, amniotic fluid, and placenta. MSCs are the leading cell source for stem cell therapy due to their regenerative and immunomodulatory properties, their low risk of tumorigenesis and lack of ethical constraints. However, clinical applications of MSCs remain limited. MSC therapeutic development continues to pose challenges in terms of preparation, purity, consistency, efficiency, reproducibility, processing time and scalability. Additionally, there are issues with their poor engraftment and survival in sites of disease or damage that limit their capacity to directly replace damaged cells. A key recent development in MSC research, however, is the now widely accepted view that MSCs primarily exert therapeutic effects via paracrine factor secretion. One of the major paracrine effectors are extracellular vesicles (EVs). EVs represent a potential cell-free alternative to stem cell therapy but are also rapidly emerging as a novel therapeutic platform in their own right, particularly in the form of engineered EVs (EEVs) tailored to target a broad range of clinical indications. However, the development of EVs and EEVs for therapeutic application still faces a number of hurdles, including the establishment of a consistent, scalable cell source, and the development of robust GMP-compliant upstream and downstream manufacturing processes. In this review we will highlight the clinical challenges of MSC therapeutic development and discuss how EVs and EEVs can overcome the challenges faced in the clinical application of MSCs.

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