Stem cell investigationPub Date : 2022-10-28eCollection Date: 2022-01-01DOI: 10.21037/sci-2022-033
Mawieh Hamad, Amjad Ali, Jibran Sualeh Muhammad
{"title":"BRD4 regulates the induction and maintenance of cancer stem cells in squamous cell carcinoma.","authors":"Mawieh Hamad, Amjad Ali, Jibran Sualeh Muhammad","doi":"10.21037/sci-2022-033","DOIUrl":"https://doi.org/10.21037/sci-2022-033","url":null,"abstract":"","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/08/sci-09-2022-033.PMC9640355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40710815","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}
M. Viveiros, M. M. Viveiros, Márcia Guimarães Silva, R. Kaneno, Natália Porfírio Avelino, C. Rainho, S. Schellini
{"title":"Expression of inflammatory cytokines in mesenchymal stem cells derived from proximal humerus fractures.","authors":"M. Viveiros, M. M. Viveiros, Márcia Guimarães Silva, R. Kaneno, Natália Porfírio Avelino, C. Rainho, S. Schellini","doi":"10.21037/sci-2021-031","DOIUrl":"https://doi.org/10.21037/sci-2021-031","url":null,"abstract":"Background\u0000Mesenchymal stem cells (MSCs) are an excellent treatment option for a wide variety of orthopaedic conditions. This study aimed to establish if bone marrow MSCs obtained from proximal humerus fractures can be an alternative source for obtaining primary cultures of human MSCs.\u0000\u0000\u0000Methods\u0000Human bone marrow was obtained during osteosynthesis surgeries on closed proximal humerus fractures within 48 hours of injury. MSCs were harvested using the Ficoll gradient separation protocol and in vitro cultured until the third passage. Then, the cells were immunophenotyped by flow cytometry using stem cell specific surface markers. The cells were also induced to differentiate into osteoblasts and adipocytes for the characterization and confirmation of MSCs. The production of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) was assessed using enzyme-linked immunosorbent assay (ELISA) in the supernatant of the cultures after 3, 5 or 7 days.\u0000\u0000\u0000Results\u0000Immunophenotyping showed high expression of the stem cell surface markers CD73, CD90, and CD105 and negative or very low expression of CD34, CD45, CD11b, CD19, and human leukocyte antigen (HLA)-DR. The bone marrow derived MSCs were able to differentiate into osteoblasts and adipocytes. The quantification of secreted cytokines revealed that IL-8 was the most produced cytokine, followed by IL-6 and IL-10 at similar quantities and lower levels of IL-1β. TNF-α and IFN-γ were not detected.\u0000\u0000\u0000Conclusions\u0000Proximal humerus fractures can be an alternative source for the collection of bone marrow MSCs. The cytokine production of these cells is very similar to the production profile of fracture haematomas previously reported and may be used for improving bone repair.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46562372","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}
Nikolaos P. Karvelas, Samuel Bennett, G. Politis, Nikolaos-Iasonas Kouris, Christo Kole
{"title":"Advances in stem cell therapy in Alzheimer's disease: a comprehensive clinical trial review.","authors":"Nikolaos P. Karvelas, Samuel Bennett, G. Politis, Nikolaos-Iasonas Kouris, Christo Kole","doi":"10.21037/sci-2021-063","DOIUrl":"https://doi.org/10.21037/sci-2021-063","url":null,"abstract":"Alzheimer's disease (AD) is the most common type of dementia responsible for more than 121,499 deaths from AD in 2019 making AD the sixth-leading cause in the United States. AD is a progressive neurodegenerative disorder characterized by decline of memory, behavioral impairments that affects a person's ability to function independently ultimately leading to death. The current pressing need for a treatment for (AD) and advances in the field of cell therapy, has rendered stem cell therapeutics a promising field of research. Despite advancements in stem cell technology, confirmed by encouraging pre-clinical utilization of stem cells in AD animal models, the number of clinical trials evaluating the efficacy of stem cell therapy is limited, with the results of many ongoing clinical trials on cell therapy for AD still pending. Mesenchymal stem cells (MSCs) have been the main focus in these studies, reporting encouraging results concerning safety profile, however their efficacy remains unproven. In the current article we review the latest advances regarding different sources of stem cell therapy and present a comprehensive list of every available clinical trial in national and international registries. Finally, we discuss drawbacks arising from AD pathology and technical limitations that hinder the transition of stem cell technology from bench to bedside. Our findings emphasize the need to increase clinical trials towards uncovering the mode of action and the underlying therapeutic mechanisms of transplanted cells as well as the molecular mechanisms controlling regeneration and neuronal microenvironment.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46012397","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}
Vikram Sumbly, Ian Landry, Christina Sneed, Qamar Iqbal, Anu Verma, Tenzin Dhokhar, Adeel Masood, Akshay Amaraneni
{"title":"Leukemic stem cells and advances in hematopoietic stem cell transplantation for acute myeloid leukemia: a narrative review of clinical trials.","authors":"Vikram Sumbly, Ian Landry, Christina Sneed, Qamar Iqbal, Anu Verma, Tenzin Dhokhar, Adeel Masood, Akshay Amaraneni","doi":"10.21037/sci-2022-044","DOIUrl":"https://doi.org/10.21037/sci-2022-044","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this literature review is to summarize and provide a brief overview of our current understanding of acute myeloid leukemia (AML) and the role of stem cell transplantation (SCT) in its management.</p><p><strong>Background: </strong>AML is a malignant hematological disorder that is characterized by the uncontrolled proliferation of myeloid blood cells. This disease has been associated with various risk factors such as ionizing radiation, cigarette smoke, pesticides/herbicides, and chemotherapy. SCT remains the most beneficial treatment for medically fit AML patients due to superior survival outcomes.</p><p><strong>Methods: </strong>A thorough search was conducted on PubMed, Scopus, ClinicalTrials.gov, Embase and Web of Science using related keywords. Current articles on the uses of stem cell therapy in AML patients were selected.</p><p><strong>Conclusions: </strong>Long term exposure to ionizing radiation and other harmful substances such as benzene, cigarette smoke and chemotherapeutic drugs plays an important role in AML carcinogenesis. Mutations in certain genes (e.g., <i>ASXL1</i>, <i>RUNX1</i>, <i>KIT</i>, <i>TP53</i>, <i>BCR-ABL1</i>) seem to accelerate the process as they affect normal cellular proliferation and cell death. These events may give rise to a small subpopulation of leukemic stem cells (LSC) which continuously sustain tumor development and growth. Patients who are deemed to be medically \"fit\" should receive an allogenic hematopoietic stem cell transplantation (allo-HSCT) due to improved overall survival (OS) (~50%) and decreased relapsed risk (32% <i>vs.</i> 59%). Several studies have revealed that the medically \"unfit\" may benefit from more conventional agents such as azacytidine, decitabine, venetoclax or sorafenib.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/1b/sci-09-2022-044.PMC9760414.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414555","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}
{"title":"Applying stem cell therapy in intractable diseases: a narrative review of decades of progress and challenges.","authors":"Brianna, Anna Pick Kiong Ling, Ying Pei Wong","doi":"10.21037/sci-2022-021","DOIUrl":"https://doi.org/10.21037/sci-2022-021","url":null,"abstract":"<p><strong>Background and objective: </strong>Stem cell therapy (SCT) is one of the vastly researched branches of regenerative medicine as a therapeutic tool to treat incurable diseases. With the use of human stem cells such as embryonic stem cells (ESCs), adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs), stem cell therapy aims to regenerate or repair damaged tissues and congenital defects. As stem cells are able to undergo infinite self-renewal, differentiate into various types of cells and secrete protective paracrine factors, many researchers have investigated the potential of SCT in regenerative medicine. Therefore, this review aims to provide a comprehensive review on the recent application of SCT in various intractable diseases, namely, haematological diseases, neurological diseases, diabetes mellitus, retinal degenerative disorders and COVID-19 infections along with the challenges faced in the clinical translation of SCT.</p><p><strong>Methods: </strong>An extensive search was conducted on Google scholar, PubMed and Clinicaltrials.gov using related keywords. Latest articles on stem cell therapy application in selected diseases along with their challenges in clinical applications were selected.</p><p><strong>Key content and findings: </strong><i>In vitro</i> and <i>in vivo</i> studies involving SCT are shown to be safe and efficacious in treating various diseases covered in this review. There are also a number of small-scale clinical trials that validated the positive therapeutic outcomes of SCT. Nevertheless, the effectiveness of SCT are highly variable as some SCT works best in patients with early-stage diseases while in other diseases, SCT is more likely to work in patients in late stages of illnesses. Among the challenges identified in SCT translation are uncertainty in the underlying stem cell mechanism, ethical issues, genetic instability and immune rejection.</p><p><strong>Conclusions: </strong>SCT will be a revolutionary treatment in the future that will provide hope to patients with intractable diseases. Therefore, studies ought to be done to ascertain the long-term effects of SCT while addressing the challenges faced in validating SCT for clinical use. Moreover, as there are many studies investigating the safety and efficacy of SCT, future studies should look into elucidating the regenerative and reparative capabilities of stem cells which largely remains unknown.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552054/pdf/sci-09-2022-021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10640367","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}
Maria Siemionow, Sonia Brodowska, Klaudia Różczka, Claire Roesler
{"title":"Creation of human hematopoietic chimeric cell (HHCC) line as a novel strategy for tolerance induction in transplantation.","authors":"Maria Siemionow, Sonia Brodowska, Klaudia Różczka, Claire Roesler","doi":"10.21037/sci-2022-026","DOIUrl":"https://doi.org/10.21037/sci-2022-026","url":null,"abstract":"<p><strong>Background: </strong>Cell-based and chimerism-based therapies represent a promising approach for tolerance induction in transplantation. We propose a new cell therapy of the <i>ex vivo</i> created human hematopoietic chimeric cells (HHCC) as an alternative approach to bone marrow (BM)-based therapies in support of solid organ and vascularized composite allotransplantation (VCA). This study aimed to characterize <i>in vitro</i> the phenotype, genotype, clonogenic, and tolerogenic properties of HHCC.</p><p><strong>Methods: </strong>Thirty <i>ex vivo</i> fusions of CD34<sup>+</sup> cells from two unrelated human BM donors were performed. CD34<sup>+</sup> cells were stained separately with PKH26 and PKH67 membrane dyes and fused using polyethylene glycol (PEG). Creation of human HHCC and chimeric state was confirmed by flow cytometry (FC), confocal microscopy (CM) and electron microscopy (EM). HHCC's phenotype (CD34, CD133, CD117, CD4, CD19, CD4/CD25) was assessed by FC, viability by Trypan Blue, LIVE/DEAD and apoptosis by AnnexinV/Sytox Blue and TUNEL assay, while mixed lymphocyte reaction (MLR) assay assessed HHCC's immunogenicity and tolerogenic properties. HHCC differentiation, proliferation and clonogenic potential were assessed by the colony forming unit (CFU). Polyploidy was evaluated by fluorescence in situ hybridization (FISH), whereas polymerase chain reaction-reverse sequence-specific oligonucleotide probe (PCR-rSSOP) and short tandem repeats-polymerase chain reaction (STR-PCR) assessed HHCC's genotype, and chimerism. Reverse transcription polymerase chain reaction (RT-PCR) analyzed cytokines secretion [interleukin (IL)-10, transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α)] up to 14 days post-fusion.</p><p><strong>Results: </strong>FC and CM confirmed creation of HHCC by fusion of CD34<sup>+</sup> cells from two unrelated human donors. After fusion, maintenance of hematopoietic markers and increased expression of Treg-cells (CD4/CD25) was confirmed. Moreover, high HHCC viability (99%) and a low apoptosis rate (1.2%) were revealed HHCC presented decreased immunogenicity by MLR, and significant, 40-fold increase of IL-10 the pro-tolerogenic cytokine at 21 days after fusion (RT-PCR) P<0.0001. The number of polyploid cells was negligible (0.48%). PCR-rSSOP of HHCC after fusion confirmed presence of human leukocyte antigen (HLA) class I and class II-alleles and presence of the loci specific for both CD34<sup>+</sup> cells BM donors by STR-PCR.</p><p><strong>Conclusions: </strong>We have created a new hematopoietic cell line of HHCC from two unrelated human donors, and have successfully characterized <i>in vitro</i>, viability, phenotype, genotype, clonogenic, and tolerogenic properties of HHCC. These unique immunomodulatory and tolerogenic properties introduce HHCC as a novel therapeutic approach for tolerance induction in VCA and solid organ transplantation.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/b8/sci-09-2022-026.PMC9813662.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499443","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}
{"title":"Understanding pancreatic cancer stem cells and their role in carcinogenesis: a narrative review.","authors":"Vikram Sumbly, Ian Landry","doi":"10.21037/sci-2021-067","DOIUrl":"https://doi.org/10.21037/sci-2021-067","url":null,"abstract":"Objective\u0000The purpose of this review article is to describe the pathogenesis of pancreatic cancer and to better understand the role of abnormal stem cells in the development of pancreatic cancer.\u0000\u0000\u0000Background\u0000Pancreatic cancer is a highly fatal disease that is caused by the uncontrolled proliferation of pancreatic exocrine or neuroendocrine glands. It is believed that pancreatic cancers arise from a small population of abnormal cancer stem cells (CSCs) that promote tumorigenesis, tumor metastasis and therapeutic resistance. The molecular markers CD133, CXCR4, DCLK1, c-MET, ABCG2 and Lgr5 are routinely used to detected and observe the behaviours of pancreatic cancer stem cells (PCSCs).\u0000\u0000\u0000Methods\u0000A comprehensive search was performed on PubMed, Google Scholar, Scopus, Clinicaltrials.gov and Web of Science using related keywords. Articles focusing on PCSCs and pancreatic cancer pathogenesis, biochemistry and clinical trials were selected.\u0000\u0000\u0000Conclusions\u0000Although very little is known about the exact cause of pancreatic cancer, PCSCs seem to play an important role in carcinogenesis. Mutated biochemical cascades include Sonic Hedgehog, K-RAS-JNK, DLL4/Notch and Nodal/Activin. Several clinical trials are trying to determine if the transplantation of hematopoietic stem cell or peripheral stem cells could be useful for the treatment of such an aggressive tumor.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45070296","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}
Stem cell investigationPub Date : 2021-12-30eCollection Date: 2021-01-01DOI: 10.21037/sci-2020-049
Mahdieh-Sadat Moosavi, Fatemeh Tavakol
{"title":"Literature review of cancer stem cells in oral lichen planus: a premalignant lesion.","authors":"Mahdieh-Sadat Moosavi, Fatemeh Tavakol","doi":"10.21037/sci-2020-049","DOIUrl":"https://doi.org/10.21037/sci-2020-049","url":null,"abstract":"<p><strong>Objective: </strong>As there is no review study about cancer stem cells (CSCs) involved in the pathogenesis of oral lichen planus (OLP), for the first time we review the role of these cells in OLP and this hypothesis may be a clue for the evaluation of the premalignancy of OLP.</p><p><strong>Background: </strong>Cellular mediated immune responses are the main etiopathogenesis in OLP and it is a potentially premalignant lesion. One of the factors proposed in the pathogenesis of OLP and the comparable trend of this autoimmune disease to squamous cell carcinoma (SCC) are CSCs. CSCs have been detected in several solid tumors including head and neck cancers, and have special characteristics including metastasis and resistance to chemotherapy.</p><p><strong>Methods: </strong>Related keywords were searched and risk of bias assessment was done for each study.</p><p><strong>Conclusions: </strong>Among all of the studies reviewed in this article, all markers had increased expression in OLP compared to controls that are consistent with SCC. Only CD44 was in contradiction to other papers, in which different expression of CD44 strains was measured in different samples such as saliva and tissue. Based on the results of this review and more studies in the future by investigating the levels of these markers in OLP, it may be possible to determine the prognosis and course of the disease for each patient individually.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743864/pdf/sci-08-2020-049.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715978","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}