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BRD4 regulates the induction and maintenance of cancer stem cells in squamous cell carcinoma. BRD4调控鳞状细胞癌中肿瘤干细胞的诱导和维持。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-28 eCollection Date: 2022-01-01 DOI: 10.21037/sci-2022-033
Mawieh Hamad, Amjad Ali, Jibran Sualeh Muhammad
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引用次数: 0
Eph receptor B2 (EPHB2) regulates cancer stem cell-like properties in hepatocellular carcinoma. Eph受体B2 (EPHB2)在肝细胞癌中调控肿瘤干细胞样特性。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-19 eCollection Date: 2022-01-01 DOI: 10.21037/sci-2022-031
Jhin Jieh Lim, Edward Kai-Hua Chow, Tan Boon Toh
© Stem Cell Investigation. All rights reserved. Stem Cell Investig 2022;9:5 | https://dx.doi.org/10.21037/sci-2022-031 Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high mortality rates globally. Poor prognosis is associated with eventual treatment resistance and disease relapse, which are often attributed to the presence of a small subset of tumor cells characterized by stem cell-like phenotypes, commonly known as cancer stem cells (CSCs). CSCs possess several key traits such as self-renewing potential, ability to initiate tumor growth, and resistance to conventional therapies targeted at rapidly proliferating cells that form the tumor bulk. In recent years, significant advances have been made in understanding the biology of different tumor CSCs and their corresponding markers, as well as how they interact with the tumor microenvironment. As increasing evidence show that long-term tumor eradication requires eliminating not just the proliferative cells but also the tumor-initiating subpopulations (1,2), greater focus has been placed on developing therapeutic strategies that target CSCs, with potential for future clinical implementation. An important aspect of specifically targeting these tumor-initiating cells rely on the use of cell surface markers. Studies on liver CSCs have uncovered various cell surface antigens such as EpCAM, CD90, CD47, CD13, CD24, and CD133 that identify subpopulations of tumor-initiating cells in HCC (3-8). However, not all cell surface markers are functionally involved in regulating CSC phenotypes in HCC, and specific small molecule inhibitors against them are scarce. In a recent study by Leung et al. (9), the authors identified a novel CSC target for HCC, Eph receptor B2 (EPHB2), that not only acts as a membrane-bound CSC marker but also plays regulatory roles in promoting stemness properties in liver tumor cells. EPHB2 expression was found to increase progressively from normal liver to cirrhotic liver and to HCC in human and mouse models (9). EPHB2 belongs to a large family of Eph receptor tyrosine kinases, which associate with membranebound ephrin ligands through cell-cell contact, leading to bidirectional intracellular signaling and activation of subsequent downstream signaling cascades (10). Eph receptors are involved in various cellular functions and processes, including cellular adhesion, cell migration, vascular development, cell proliferation and survival (10). The complexity of Eph receptor signaling also extends to its involvement in cancer. In fact, the role of EPHB2 in cancer is controversial, as it has been demonstrated to play both tumor-promoting and tumor-suppressive functions depending on the cellular context. In cancers such as glioblastoma, breast cancer, cervical cancer, and cutaneous squamous cell carcinoma, EPHB2 is overexpressed and promotes tumor progression and invasiveness (11-14). In contrast, EPHB2 exerts inhibitory effects on tumor cell migration and invasion, a
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引用次数: 0
Expression of inflammatory cytokines in mesenchymal stem cells derived from proximal humerus fractures. 炎性细胞因子在肱骨近端骨折间充质干细胞中的表达。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-04-01 DOI: 10.21037/sci-2021-031
M. Viveiros, M. M. Viveiros, Márcia Guimarães Silva, R. Kaneno, Natália Porfírio Avelino, C. Rainho, S. Schellini
BackgroundMesenchymal 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.MethodsHuman 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.ResultsImmunophenotyping 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.ConclusionsProximal 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.
背景间充质干细胞(MSCs)是治疗各种骨科疾病的绝佳选择。本研究旨在确定从肱骨近端骨折中获得的骨髓间充质干细胞是否可以作为获得人间充质细胞原代培养物的替代来源。使用Ficoll梯度分离方案收获MSC,并在体外培养至第三代。然后,使用干细胞特异性表面标记物通过流式细胞术对细胞进行免疫表型分析。还诱导细胞分化为成骨细胞和脂肪细胞,用于MSC的表征和确认。3、5或7天后,使用酶联免疫吸附试验(ELISA)评估培养物上清液中细胞因子白细胞介素(IL)-1β、IL-6、IL-8、IL-10、肿瘤坏死因子α(TNF-α)和干扰素γ(IFN-γ)的产生。结果免疫表型显示干细胞表面标志物CD73、CD90和CD105高表达,CD34、CD45、CD11b、CD19和人类白细胞抗原(HLA)-DR阴性或极低表达。骨髓来源的MSCs能够分化为成骨细胞和脂肪细胞。分泌细胞因子的定量显示,IL-8是产生最多的细胞因子,其次是IL-6和IL-10,数量相似,IL-1β水平较低。未检测到TNF-α和IFN-γ。结论肱骨近端骨折可作为骨髓间充质干细胞采集的替代来源。这些细胞的细胞因子产生与先前报道的骨折血肿的产生情况非常相似,可用于改善骨修复。
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引用次数: 1
Advances in stem cell therapy in Alzheimer's disease: a comprehensive clinical trial review. 干细胞治疗阿尔茨海默病的进展:一项全面的临床试验综述。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-02-01 DOI: 10.21037/sci-2021-063
Nikolaos P. Karvelas, Samuel Bennett, G. Politis, Nikolaos-Iasonas Kouris, Christo Kole
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.
阿尔茨海默病(AD)是最常见的痴呆类型,2019年有121499多人死于AD,使AD成为美国第六大病因。AD是一种进行性神经退行性疾病,其特征是记忆力下降,行为障碍会影响一个人的独立功能,最终导致死亡。目前对(AD)治疗的迫切需求和细胞治疗领域的进展,使干细胞治疗成为一个有前途的研究领域。尽管干细胞技术取得了进步,并通过鼓励干细胞在AD动物模型中的临床前利用得到了证实,但评估干细胞治疗疗效的临床试验数量有限,许多正在进行的AD细胞治疗临床试验的结果仍悬而未决。间充质干细胞(MSC)一直是这些研究的主要焦点,报告了令人鼓舞的安全性结果,但其疗效尚未得到证实。在当前的文章中,我们回顾了不同干细胞治疗来源的最新进展,并在国家和国际注册中心提供了每一项可用临床试验的综合列表。最后,我们讨论了AD病理学产生的缺陷以及阻碍干细胞技术从台架向床边过渡的技术限制。我们的发现强调了增加临床试验的必要性,以揭示移植细胞的作用模式和潜在的治疗机制,以及控制再生和神经元微环境的分子机制。
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引用次数: 4
Is there a role for allogeneic hematopoietic stem cell transplantation for refractory follicular lymphoma? 异体造血干细胞移植对难治性滤泡性淋巴瘤有作用吗?
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.21037/sci-2022-041
Yang Yang, Xia Bi, Mia Gergis, Usama Gergis
© Stem Cell Investigation. All rights reserved. Stem Cell Investig 2022;9:9 | https://dx.doi.org/10.21037/sci-2022-041 Follicular lymphoma (FL) is the most common indolent lymphoma. Although the prognosis for FL is favorable, approximately 20% of patients relapse or progress within 24 months of initial chemoimmunotherapy. Early relapse is a poor prognostic indicator with a 5-year overall survival (OS) of 50%. First relapse is usually treated with salvage chemoimmunotherapy followed by autologous stem cell transplantation (autoSCT) for chemo-responsive disease. Patients who have chemo-resistant disease or are unable to tolerate autoSCT, have a dismal prognosis. Allogeneic SCT (alloSCT) is not routinely recommended for FL patients due to the high treatment related mortality (TRM) with myeloablative conditioning regimen (MAC). The development of reduced intensity regimen (RIC) and non-myeloablative regimen (NMA) has markedly reduced TRM in alloSCT. However, the role of alloSCT vs. autoSCT in the treatment of relapsed/refractory FL (R/R FL) remains unclear. Published in Clinical Cancer Research in August 2021, the MD Anderson group retrospectively analyzed the outcomes of R/R FL patients who underwent either alloSCT or autoSCT and concluded that patients who received alloSCT had superior outcomes to those who received autoSCT (1). Khouri et al. group evaluated 194 patients with R/R FL who received NMA alloSCT (n=98) vs. autoSCT (n=96) at the MD Anderson Cancer Center between January, 2000 and December, 2017. The median follow-up was 108 months for alloSCT and 102 months for autoSCT. The OS and progression-free survival (PFS) were significantly better in patients who received alloSCT compared to autoSCT. The 8-year relapse rate was significantly lower in the alloSCT group and non-relapse mortality (NRM) between the two groups was similar. The OS for the alloSCT group was 62%, which is similar to the 61% OS reported by the large CIBMTR/EBMT study examining alloSCT in 1,567 patients with R/R FL (2). However, a similar study by the CIBMTR comparing alloSCT to autoSCT in early relapse FL reported similar OS in matched related donor (MRD) alloSCT (73%) and autoSCT (70%) and inferior OS in matched unrelated donor (MUD) alloSCT (49%). It is worth mentioning that the alloSCT group included more chemo refractory patients than the autoSCT group (40% vs. 23%) (3). It is impossible to compare the results of the referenced three trials (1-3) due to the inherent heterogeneity in methodology (single center vs. registry studies), patient, disease and transplant characteristics. In Khouri et al., the alloSCT patients were rightly highly selected with a median age of 53 years and only 24% of patients aged above 60. Additionally, most of the patients were enrolled on clinical trials, only 11% had a comorbidity index ≥3 and 16% had chemo refractory disease. Older age, poor performance status and chemo refractory disease have previously been shown to be predictors of wors
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引用次数: 0
Leukemic stem cells and advances in hematopoietic stem cell transplantation for acute myeloid leukemia: a narrative review of clinical trials. 白血病干细胞和造血干细胞移植治疗急性髓系白血病的进展:临床试验的叙述性回顾。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.21037/sci-2022-044
Vikram Sumbly, Ian Landry, Christina Sneed, Qamar Iqbal, Anu Verma, Tenzin Dhokhar, Adeel Masood, Akshay Amaraneni

Objective: 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.

Background: 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.

Methods: 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.

Conclusions: 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., ASXL1, RUNX1, KIT, TP53, BCR-ABL1) 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% vs. 59%). Several studies have revealed that the medically "unfit" may benefit from more conventional agents such as azacytidine, decitabine, venetoclax or sorafenib.

目的:本文献综述的目的是总结并简要概述我们目前对急性髓性白血病(AML)的理解以及干细胞移植(SCT)在其治疗中的作用。背景:AML是一种恶性血液系统疾病,其特征是髓系血细胞不受控制的增殖。这种疾病与多种危险因素有关,如电离辐射、香烟烟雾、杀虫剂/除草剂和化疗。SCT仍然是医学上适合AML患者的最有益的治疗方法,因为它具有优越的生存结果。方法:采用相关关键词在PubMed、Scopus、ClinicalTrials.gov、Embase和Web of Science上进行全面检索。我们选择了目前关于干细胞治疗在AML患者中的应用的文章。结论:长期暴露于电离辐射及苯、香烟烟雾、化疗药物等有害物质中,在AML的癌变中起重要作用。某些基因(如ASXL1、RUNX1、KIT、TP53、BCR-ABL1)的突变似乎会加速这一过程,因为它们会影响正常的细胞增殖和细胞死亡。这些事件可能导致白血病干细胞(LSC)的一小部分亚群持续维持肿瘤的发展和生长。由于总生存率(OS)提高(~50%)和复发风险降低(32%对59%),医学上认为“适合”的患者应接受同种异体造血干细胞移植(allogenic hematopoietic stem cell transplantation, alloo - hsct)。几项研究表明,医学上“不适合”的人可能会受益于更传统的药物,如阿扎胞苷、地西他滨、维尼托克拉克或索拉非尼。
{"title":"Leukemic stem cells and advances in hematopoietic stem cell transplantation for acute myeloid leukemia: a narrative review of clinical trials.","authors":"Vikram Sumbly,&nbsp;Ian Landry,&nbsp;Christina Sneed,&nbsp;Qamar Iqbal,&nbsp;Anu Verma,&nbsp;Tenzin Dhokhar,&nbsp;Adeel Masood,&nbsp;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":"9 ","pages":"10"},"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}
引用次数: 1
Applying stem cell therapy in intractable diseases: a narrative review of decades of progress and challenges. 应用干细胞治疗顽固性疾病:几十年的进展和挑战的叙述回顾。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.21037/sci-2022-021
Brianna, Anna Pick Kiong Ling, Ying Pei Wong

Background and objective: 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.

Methods: 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.

Key content and findings: In vitro and in vivo 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.

Conclusions: 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.

背景与目的:干细胞治疗作为治疗不治之症的一种治疗工具,是再生医学中被广泛研究的分支之一。利用人类干细胞,如胚胎干细胞(ESCs)、成体干细胞(ASCs)和诱导多能干细胞(iPSCs),干细胞治疗旨在再生或修复受损组织和先天性缺陷。由于干细胞能够无限自我更新,分化成各种类型的细胞,并分泌保护性旁分泌因子,许多研究人员已经研究了SCT在再生医学中的潜力。因此,本文旨在综述近年来SCT在血液病、神经系统疾病、糖尿病、视网膜退行性疾病、COVID-19感染等各种顽固性疾病中的应用,以及SCT在临床转化中面临的挑战。方法:使用相关关键词在Google scholar、PubMed和Clinicaltrials.gov上进行广泛检索。选择了干细胞治疗在特定疾病中的应用及其在临床应用中的挑战的最新文章。主要内容和发现:体外和体内研究表明,SCT在治疗本综述中涉及的各种疾病方面是安全有效的。也有一些小规模的临床试验证实了SCT的积极治疗效果。然而,SCT的有效性是高度可变的,因为一些SCT在早期疾病患者中效果最好,而在其他疾病中,SCT更可能在晚期疾病患者中起作用。在SCT翻译中发现的挑战包括潜在干细胞机制的不确定性、伦理问题、遗传不稳定性和免疫排斥。结论:SCT将是未来一种革命性的治疗方法,将为顽固性疾病患者带来希望。因此,应该进行研究以确定SCT的长期效果,同时解决验证SCT临床应用所面临的挑战。此外,由于有许多研究调查了SCT的安全性和有效性,未来的研究应该着眼于阐明干细胞的再生和修复能力,这在很大程度上仍然是未知的。
{"title":"Applying stem cell therapy in intractable diseases: a narrative review of decades of progress and challenges.","authors":"Brianna,&nbsp;Anna Pick Kiong Ling,&nbsp;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":"9 ","pages":"4"},"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}
引用次数: 4
Creation of human hematopoietic chimeric cell (HHCC) line as a novel strategy for tolerance induction in transplantation. 建立人造血嵌合细胞(HHCC)系作为移植耐受诱导的新策略。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.21037/sci-2022-026
Maria Siemionow, Sonia Brodowska, Klaudia Różczka, Claire Roesler

Background: Cell-based and chimerism-based therapies represent a promising approach for tolerance induction in transplantation. We propose a new cell therapy of the ex vivo 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 in vitro the phenotype, genotype, clonogenic, and tolerogenic properties of HHCC.

Methods: Thirty ex vivo fusions of CD34+ cells from two unrelated human BM donors were performed. CD34+ 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.

Results: FC and CM confirmed creation of HHCC by fusion of CD34+ 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+ cells BM donors by STR-PCR.

Conclusions: We have created a new hematopoietic cell line of HHCC from two unrelated human donors, and have successfully characterized in vitro, 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.

背景:基于细胞和嵌合的治疗是一种很有前途的移植耐受诱导方法。我们提出了一种新的细胞疗法,即体外培养的人造血嵌合细胞(HHCC),作为骨髓(BM)基础治疗的替代方法,支持实体器官和血管化复合异体移植(VCA)。本研究旨在体外鉴定HHCC的表型、基因型、克隆性和耐受性。方法:对来自两名无亲缘关系的人骨髓供体的30例CD34+细胞进行体外融合。CD34+细胞分别用PKH26和PKH67膜染料染色,聚乙二醇(PEG)融合。通过流式细胞术(FC)、共聚焦显微镜(CM)和电镜(EM)证实了人HHCC的形成和嵌合状态。采用FC法检测HHCC的表型(CD34、CD133、CD117、CD4、CD19、CD4/CD25),台泛蓝法检测细胞活力,AnnexinV/Sytox Blue和TUNEL法检测细胞凋亡,混合淋巴细胞反应(MLR)法检测HHCC的免疫原性和耐受性。采用菌落形成单位(colony forming unit, CFU)评价HHCC的分化、增殖和克隆潜能。采用荧光原位杂交(FISH)评估多倍体,聚合酶链反应-反序列特异性寡核苷酸探针(PCR-rSSOP)和短串联重复聚合酶链反应(STR-PCR)评估HHCC的基因型和嵌合性。逆转录聚合酶链反应(RT-PCR)分析融合后14天细胞因子的分泌[白细胞介素(IL)-10,转化生长因子-β (TGF-β)和肿瘤坏死因子-α (TNF-α)]。结果:FC和CM证实了两名无亲缘关系的人类供者的CD34+细胞融合产生HHCC。融合后,证实造血标志物维持,treg细胞(CD4/CD25)表达增加。此外,高HHCC活力(99%)和低凋亡率(1.2%)显示,MLR显示HHCC免疫原性下降,融合(RT-PCR)后21天(STR-PCR) P+细胞BM供者的IL-10显着增加40倍。结论:我们从两个无亲缘关系的人类供体中建立了一种新的HHCC造血细胞系,并成功地在体外鉴定了HHCC的活力、表型、基因型、克隆性和耐受性。这些独特的免疫调节和耐受性特性使HHCC成为VCA和实体器官移植中耐受性诱导的新治疗方法。
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引用次数: 2
Understanding pancreatic cancer stem cells and their role in carcinogenesis: a narrative review. 了解胰腺癌干细胞及其在癌变中的作用:综述。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.21037/sci-2021-067
Vikram Sumbly, Ian Landry
ObjectiveThe 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.BackgroundPancreatic 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).MethodsA 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.ConclusionsAlthough 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.
目的综述胰腺癌的发病机制,进一步了解异常干细胞在胰腺癌发生发展中的作用。胰腺癌是一种高度致命的疾病,由胰腺外分泌腺或神经内分泌腺不受控制的增殖引起。人们认为,胰腺癌起源于一小部分异常肿瘤干细胞(CSCs),它们促进肿瘤发生、肿瘤转移和治疗抵抗。CD133、CXCR4、DCLK1、c-MET、ABCG2和Lgr5等分子标记是检测和观察胰腺癌干细胞(PCSCs)行为的常规方法。方法采用相关关键词在PubMed、谷歌Scholar、Scopus、Clinicaltrials.gov和Web of Science进行综合检索。选择PCSCs与胰腺癌发病机制、生物化学和临床试验相关的文章。结论虽然对胰腺癌的确切病因知之甚少,但PCSCs似乎在胰腺癌发生中起着重要作用。突变的生化级联包括Sonic Hedgehog、K-RAS-JNK、DLL4/Notch和Nodal/Activin。一些临床试验正在试图确定移植造血干细胞或外周干细胞是否可用于治疗这种侵袭性肿瘤。
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引用次数: 5
Literature review of cancer stem cells in oral lichen planus: a premalignant lesion. 口腔扁平苔藓:一种癌前病变:肿瘤干细胞的文献综述。
Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-12-30 eCollection Date: 2021-01-01 DOI: 10.21037/sci-2020-049
Mahdieh-Sadat Moosavi, Fatemeh Tavakol

Objective: 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.

Background: 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.

Methods: Related keywords were searched and risk of bias assessment was done for each study.

Conclusions: 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.

目的:由于目前尚无关于肿瘤干细胞(cancer stem cells, CSCs)参与口腔扁平苔藓(oral lichen planus, OLP)发病机制的综述研究,我们首次综述了这些细胞在OLP中的作用,这一假设可能为评估OLP的恶性前病变提供线索。背景:细胞介导的免疫反应是OLP的主要发病机制,它是一种潜在的恶性病变。在OLP的发病机制中提出的因素之一,以及这种自身免疫性疾病与鳞状细胞癌(SCC)的可比趋势是csc。CSCs已在包括头颈部肿瘤在内的多种实体肿瘤中被发现,并且具有转移和耐化疗等特殊特征。方法:检索相关关键词,对各研究进行偏倚风险评价。结论:在本文回顾的所有研究中,与对照组相比,所有标记物在OLP中的表达均增加,这与SCC一致。只有CD44与其他论文相矛盾,在不同的样本如唾液和组织中测量了不同的CD44菌株表达。基于本综述的结果以及未来通过调查OLP中这些标志物水平的更多研究,可能有可能确定每个患者的预后和病程。
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引用次数: 4
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Stem cell investigation
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