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.

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 Stem‐Cell Therapy for Esophageal Anastomotic Leakage by Autografting Stromal Cells in Fibrin Scaffold

2019 ◽  
Vol 8 (6) ◽  
pp. 548-556 ◽  
Author(s):  
Xiang Xue ◽  
Yan Yan ◽  
Ye Ma ◽  
Yang Yuan ◽  
Chunguang Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Anastomotic Leakage ◽  
Stem Cell Therapy ◽  
Stromal Cells ◽  
Fibrin Scaffold
Sign in / Sign up

Export Citation Format

Share Document