{"title":"Pilot Safety Study of an Extracellular Vesicle Isolate Product for Treatment of Osteoarthritis in Combat-Related Injuries: One Year Follow Up","authors":"J. East, M. Dordevic","doi":"10.52793/jscr.2021.2(2)-21","DOIUrl":"https://doi.org/10.52793/jscr.2021.2(2)-21","url":null,"abstract":"Objective: This is the first report on the safety and clinical efficacy of a bone marrow mesenchymal cell extracellular vesicle isolate product (XoFloTM) to treat osteoarthritis (OA). Design, Setting, and Methods: Thirty-three Navy SEAL veterans were treated with XoFlo for OA of the knee (n=58), shoulder (n=32), elbow (n=16), hip (n=12), ankle (n=8) or wrist (n=6). Four Pain and Motion Indexes were used to evaluate patients’ OA. Results: At 1-year follow-up, the average patient improved 82% in BPI, 77% in ODI, 67% in LEFS, 50% in UEFS, and 77% in QD. All improvements were statistically significant with values of p<0.001. Ninety-five percent of the improvement occurred within the first six weeks following the injection and continued through the 1-year follow-up. There were no complications or adverse events, minor or major. No patient was observed to have accelerated OA progression or made clinically worse from the XoFlo injection. Conclusions: At 1-year follow-up, a 2cc injection per joint of XoFlo appears to be safe and clinically efficacious for the treatment of patients with at least Grade 2 changes of OA utilizing the Kellgren-Lawrence scale. These patients will continue to be followed for at least two years.","PeriodicalId":92258,"journal":{"name":"Journal of stem cell research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43524362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal Stem Cell-Based Therapy For Advanced Colorectal Cancer: Potential Mechanisms Of Therapy And Associated Risks","authors":"A. Hilland, V. Gallicchio","doi":"10.52793/jscr.2021.2(2)-s4","DOIUrl":"https://doi.org/10.52793/jscr.2021.2(2)-s4","url":null,"abstract":"Despite recent advances in diagnosis and treatment, colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths due to therapy resistance. Traditional treatment methods for colon cancer include surgery, chemotherapy, and radiation therapy. However, due to the unspecific target of these strategies and the presence of therapy-resistant colon cancer stem cells in the tumor microenvironment, nearly 50% of patients exhibit tumor recurrence. Therefore, there is an urgent need for alternative methods, and targeted cell-based therapies are emerging as promising agents for the treatment of heterogeneous malignancies. In particular, mesenchymal stem cells (MSCs) have been widely investigated for their therapeutic potential in regenerative medicine due to unique biological features, including self-regeneration and differentiation potential, tumor homing capacity, and immunomodulatory and paracrine functions. However, the exact role of MSCs in cancer treatment remains controversial as they have been shown to be involved in tumor progression and inhibition at the preclinical level. This review summarizes current findings on the application of MSCbased therapy for colon cancer, with a focus on the mechanisms of action of MSCs as therapeutic agents, including paracrine action, the capacity of migration, and impact on the regulation of the human immune system. It also discusses strategies to improve MSCs therapeutic effectiveness through genetic engineering and potential risks that should be considered before clinical use.","PeriodicalId":92258,"journal":{"name":"Journal of stem cell research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47188222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell Therapy And Methods Of Stem Cell Delivery For Regeneration Of Heart Tissue Following Myocardial Infarction","authors":"Samantha Spence, V. Gallicchio","doi":"10.52793/jscr.2021.2(2)-s3","DOIUrl":"https://doi.org/10.52793/jscr.2021.2(2)-s3","url":null,"abstract":"Myocardial infarction (MI) results in irreversible loss of cardiomyocytes (CMs) and can often lead to heart failure. Due to the minimal regeneration capacity of the myocardium, novel therapeutic techniques are needed. Cell therapy has emerged as a promising treatment for MI and involves the introduction of stem cells into the infarct area where they can proliferate and regenerate functional heart tissue. These cells can be delivered by various methods, including direct injection, scaffold formation, and cell sheet preparation. Of these, cell sheet technology appears to hold the most promise as it allows for maximal cell engraftment and retention without significant harmful side effects. Furthermore, the best composition of the cell sheet has since been debated. Cell sheets composed of skeletal myoblasts (SMs), mesenchymal cells (MSCs), and pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells","PeriodicalId":92258,"journal":{"name":"Journal of stem cell research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48738694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Verbus, J. Kenyon, O. Sergeeva, Amad Awadallah, Lewis Yuan, J. Welter, A. Caplan, M. Schluchter, A. Khalil, Z. Lee
{"title":"Expression of miR-145-5p During Chondrogenesis of Mesenchymal Stem Cells.","authors":"E. Verbus, J. Kenyon, O. Sergeeva, Amad Awadallah, Lewis Yuan, J. Welter, A. Caplan, M. Schluchter, A. Khalil, Z. Lee","doi":"10.33425/2639-9512.1017","DOIUrl":"https://doi.org/10.33425/2639-9512.1017","url":null,"abstract":"Assessing the quality of tissue engineered (TE) cartilage has historically been performed by endpoint measurements including marker gene expression. Until the adoption of promoter-driven reporter constructs capable of quantitative and real time non-destructive expression analysis, temporal gene expression assessments along a timeline could not be performed on TE constructs. We further exploit this technique to utilize microRNA (miRNA or miR) through the use of firefly luciferase reporter (Luc) containing a 3' UTR perfect complementary target sequence to the mature miR-145-5p. We report the development and testing of a firefly luciferase (Luc) reporter responsive to miR-145-5p for longitudinal tracking of miR-145-5p expression throughout MSC chondrogenic differentiation. Plasmid reporter vectors containing a miR-145-5p responsive reporter (Luc reporter with a perfect complementary target sequence to the mature miR-145-5p sequence in the 3'UTR), a Luc reporter driven by a truncated Sox9 (one of the targets of miR-145-5p) promoter, or the Luc backbone (control) vector without a specific miRNA target were transfected into MSCs by electroporation. Transfected MSCs were mixed with untransfected MSC to generate chondrogenic pellets. Pellets were imaged by bioluminescent imaging (BLI) and harvested along a preset time line. The imaging signals from miR-145-5p responsive reporter and Sox9 promoter-driven reporter showed correlated time-courses (measured by BLI and normalized to Luc-control reporter; Spearman r=0.93, p=0.0002) during MSC chondrogenic differentiation. Expression analysis by qRT-PCR suggests an inverse relationship between miR-145-5p and Sox9 gene expression during MSC chondrogenic differentiation. Non-destructive cell-pellet imaging is capable of supplementing histological analyses to characterize TE cartilage. The miR-145-5p responsive reporter is relatively simple to construct and generates a consistent imaging signal responsive to miR-145-5p during MSC chondrogenesis in parallel to certain molecular and cellular events.","PeriodicalId":92258,"journal":{"name":"Journal of stem cell research","volume":"1 3 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69746403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily A Verbus, Jonathan D Kenyon, Olga Sergeeva, Amad Awadallah, Lewis Yuan, Jean F Welter, Arnold I Caplan, Mark D Schluchter, Ahmad M Khalil, Zhenghong Lee
{"title":"Expression of miR-145-5p During Chondrogenesis of Mesenchymal Stem Cells.","authors":"Emily A Verbus, Jonathan D Kenyon, Olga Sergeeva, Amad Awadallah, Lewis Yuan, Jean F Welter, Arnold I Caplan, Mark D Schluchter, Ahmad M Khalil, Zhenghong Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Assessing the quality of tissue engineered (TE) cartilage has historically been performed by endpoint measurements including marker gene expression. Until the adoption of promoter-driven reporter constructs capable of quantitative and real time non-destructive expression analysis, temporal gene expression assessments along a timeline could not be performed on TE constructs. We further exploit this technique to utilize microRNA (miRNA or miR) through the use of firefly luciferase reporter (Luc) containing a 3' UTR perfect complementary target sequence to the mature miR-145-5p. We report the development and testing of a firefly luciferase (Luc) reporter responsive to miR-145-5p for longitudinal tracking of miR-145-5p expression throughout MSC chondrogenic differentiation. Plasmid reporter vectors containing a miR-145-5p responsive reporter (Luc reporter with a perfect complementary target sequence to the mature miR-145-5p sequence in the 3'UTR), a Luc reporter driven by a truncated Sox9 (one of the targets of miR-145-5p) promoter, or the Luc backbone (control) vector without a specific miRNA target were transfected into MSCs by electroporation. Transfected MSCs were mixed with untransfected MSC to generate chondrogenic pellets. Pellets were imaged by bioluminescent imaging (BLI) and harvested along a preset time line. The imaging signals from miR-145-5p responsive reporter and Sox9 promoter-driven reporter showed correlated time-courses (measured by BLI and normalized to Luc-control reporter; Spearman r=0.93, p=0.0002) during MSC chondrogenic differentiation. Expression analysis by qRT-PCR suggests an inverse relationship between miR-145-5p and Sox9 gene expression during MSC chondrogenic differentiation. Non-destructive cell-pellet imaging is capable of supplementing histological analyses to characterize TE cartilage. The miR-145-5p responsive reporter is relatively simple to construct and generates a consistent imaging signal responsive to miR-145-5p during MSC chondrogenesis in parallel to certain molecular and cellular events.</p>","PeriodicalId":92258,"journal":{"name":"Journal of stem cell research","volume":"1 3","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926818/pdf/nihms910597.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36065106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}