{"title":"Advances in iPSC Technology in Neural Disease Modeling, Drug Screening, and Therapy.","authors":"Sihan Dai, Linhui Qiu, Vishnu Priya Veeraraghavan, Chia-Lin Sheu, Ullas Mony","doi":"10.2174/1574888X18666230608105703","DOIUrl":"10.2174/1574888X18666230608105703","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDs) including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease are all incurable and can only be managed with drugs for the associated symptoms. Animal models of human illnesses help to advance our understanding of the pathogenic processes of diseases. Understanding the pathogenesis as well as drug screening using appropriate disease models of neurodegenerative diseases (NDs) are vital for identifying novel therapies. Human-derived induced pluripotent stem cell (iPSC) models can be an efficient model to create disease in a dish and thereby can proceed with drug screening and identifying appropriate drugs. This technology has many benefits, including efficient reprogramming and regeneration potential, multidirectional differentiation, and the lack of ethical concerns, which open up new avenues for studying neurological illnesses in greater depth. The review mainly focuses on the use of iPSC technology in neuronal disease modeling, drug screening, and cell therapy.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"809-819"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal Stem Cell Therapy for Treating the Underlying Causes of Diabetes Mellitus and Its Consequences.","authors":"Diana Esquivel, Rangnath Mishra, Anand Srivastava","doi":"10.2174/1574888X18666230411111320","DOIUrl":"10.2174/1574888X18666230411111320","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a multifaceted pathological condition, which at present is being considered an epidemic disease keeping the rampant rate of its increase in almost all population groups of the world in consideration. Out of the two types of DM described, T1D is characterized as an autoimmune condition that leads to the destruction of pancreatic β-cells by macrophages and T-cells, thereby, adversely affecting the production of insulin. On the other hand, T2D, often caused by insulin resistance, is commonly related to unhealthy habits, and therefore, it can be prevented in most cases. In both of the conditions, high levels of proinflammatory cytokines like IL-6, TNF-α, and INF-ƴ, lead to chronic inflammation, and elevated oxidative stress resulting in apoptosis and destruction of tissues. Although several treatments are available to treat the symptoms, the underlying causes are not well addressed. One of the most promising approaches to tackle the ill effects and the primary causes of DM is mesenchymal stem cell (MSC) therapy. The use of MSC therapy, because of the immunomodulatory and regenerative properties recorded in this type of cells in a number of experiments carried out in animal models and clinical trials of the disease, has reported positive outcomes. This review covers the principal mechanisms of action induced during MSC therapy in reference to the described pathophysiological pathways of both T1D and T2D. In addition, how this therapeutic intervention can counteract the ill effects of this condition leading to the promotion of tissue regeneration has been covered.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"662-668"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9648478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research Progress on Cardiac Tissue Construction of Mesenchymal Stem Cells for Myocardial Infarction.","authors":"Guo-Dong Yang, Da-Shi Ma, Chun-Ye Ma, Yang Bai","doi":"10.2174/1574888X18666230823091017","DOIUrl":"10.2174/1574888X18666230823091017","url":null,"abstract":"<p><p>Heart failure is still the main complication affecting the prognosis of acute myocardial infarction (AMI), and mesenchymal stem cells (MSCs) are an effective treatment to replace necrotic myocardium and improve cardiac functioning. However, the transplant survival rate of MSCs still presents challenges. In this review, the biological characteristics of MSCs, the progress of mechanism research in the treatment of myocardial infarction, and the advances in improving the transplant survival rate of MSCs in the replacement of necrotic myocardial infarction are systematically described. From a basic to advanced clinical research, MSC transplants have evolved from a pure injection, an exosome injection, the genetic modification of MSCs prior to injection to the cardiac tissue engineering of MSC patch grafting. This study shows that MSCs have wide clinical applications in the treatment of AMI, suggesting improved myocardial tissue creation. A broader clinical application prospect will be explored and developed to improve the survival rate of MSC transplants and myocardial vascularization.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"942-958"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FBLN5 was Regulated by PRDM9, and Promoted Senescence and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.","authors":"Mengyao Zhao, Rong Rong, Chen Zhang, Haoqing Yang, Xiao Han, Zhipeng Fan, Ying Zheng, Jianpeng Zhang","doi":"10.2174/1574888X18666230822100054","DOIUrl":"10.2174/1574888X18666230822100054","url":null,"abstract":"<p><strong>Objectives: </strong>Periodontal ligament stem cells (PDLSCs) are ideal seed cells for periodontal tissue regeneration. Our previous studies have indicated that the histone methyltransferase PRDM9 plays an important role in human periodontal ligament stem cells (hPDLSCs). Whether FBLN5, which is a downstream gene of PRDM9, also has a potential impact on hPDLSCs is still unclear.</p><p><strong>Methods: </strong>Senescence was assessed using β-galactosidase and Enzyme-linked immunosorbent assay (ELISA). Osteogenic differentiation potential of hPDLSCs was measured through Alkaline phosphatase (ALP) activity assay and Alizarin red detection, while gene expression levels were evaluated using western blot and RT-qPCR analysis.</p><p><strong>Results: </strong>FBLN5 overexpression promoted the osteogenic differentiation and senescence of hPDLSCs. FBLN5 knockdown inhibited the osteogenic differentiation and senescence of hPDLSCs. Knockdown of PRDM9 decreased the expression of FBLN5 in hPDLSCs and inhibited senescence of hPDLSCs. Additionally, both FBLN5 and PRDM9 promoted the expression of phosphorylated p38 MAPK, Erk1/2 and JNK. The p38 MAPK pathway inhibitor SB203580 and the Erk1/2 pathway inhibitor PD98059 have the same effects on inhibiting the osteogenic differentiation and senescence of hPDLSCs. The JNK pathway inhibitor SP600125 reduced the senescence of hPDLSCs.</p><p><strong>Conclusion: </strong>FBLN5 promoted senescence and osteogenic differentiation of hPDLSCs via activation of the MAPK signaling pathway. FBLN5 was positively targeted by PRDM9, which also activated the MAPK signaling pathway.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"417-425"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10407784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exosome-mediated Repair of Intervertebral Disc Degeneration: The Potential Role of miRNAs.","authors":"Han-Shi Wang, Shu Lin, Hai-Ming Yu","doi":"10.2174/1574888X18666230504094233","DOIUrl":"10.2174/1574888X18666230504094233","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a serious condition that manifests as low back pain, intervertebral disc protrusion, and spinal canal stenosis. At present, the main treatment methods for IVDD are surgical interventions such as discectomy, total disc replacement, and spinal fusion. However, these interventions have shown limitations, such as recurrent lumbar disc herniation after discectomy, lesions in adjacent segments, and failure of fixation. To overcome these shortcomings, researchers have been exploring stem cell transplantation therapy, such as mesenchymal stem cell (MSC) transplantation, but the treatment results are still controversial. Therefore, researchers are in search of new methods that are more efficient and have better outcomes. The exosomes from stem cells contain a variety of bioactive molecules that mediate cell interactions, and these components have been investigated for their potential therapeutic role in the repair of various tissue injuries. Recent studies have shown that MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on nucleus pulposus cells, annulus fibrosus, and cartilage endplate. miRNAs play a role in many cell activities, such as cell proliferation, apoptosis, and cytokine release, by acting on mRNA translation, and they may have immense therapeutic potential, especially when combined with stem cell therapy. This article reviews the current status of research on intervertebral disc repair, especially with regard to the latest research findings on the molecular biological mechanisms of miRNAs in MSC-derived exosomes in intervertebral disc repair.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"798-808"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9425084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amin Firoozi, Mehri Shadi, Zohre Aghaei, Mohammad Reza Namavar
{"title":"Conditioned Media Therapy in Alzheimer's Disease: Current Findings and Future Challenges.","authors":"Amin Firoozi, Mehri Shadi, Zohre Aghaei, Mohammad Reza Namavar","doi":"10.2174/1574888X18666230523155659","DOIUrl":"10.2174/1574888X18666230523155659","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by a reduction in cognition and memory. Till now, there is no definite cure for AD, although, there are treatments available that may improve some symptoms. Currently, in regenerative medicine stem cells are widely used, mainly for treating neurodegenerative diseases. There are numerous forms of stem cells to treat AD aiming at the expansion of the treatment methods for this particular disease. Since 10 years ago, science has gained abundant knowledge to treat AD by understanding the sorts of stem cells, methods, and phasing of injection. Besides, due to the side effects of stem cell therapy like the potentiation for cancer, and as it is hard to follow the cells through the matrix of the brain, researchers have presented a new therapy for AD. They prefer to use conditioned media (CM) that are full of different growth factors, cytokines, chemokines, enzymes, etc. without tumorigenicity or immunogenicity such as stem cells. Another benefit of CM is that CM could be kept in the freezer, easily packaged, and transported, and doesn't need to fit with the donor. Due to the beneficial effects of CM, in this paper, we intend to evaluate the effects of various types of CM of stem cells on AD.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"700-711"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9570489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Potential of Stem Cells in Treating Breast Cancer.","authors":"Deepika Yadav, Pramod Kumar Sharma, Prem Shankar Mishra, Rishabha Malviya","doi":"10.2174/1574888X18666230428094056","DOIUrl":"10.2174/1574888X18666230428094056","url":null,"abstract":"<p><p>There has been a lot of interest in stem cell therapy as a means of curing disease in recent years. Despite extensive usage of stem cell therapy in the treatment of a wide range of medical diseases, it has been hypothesized that it plays a key part in the progression of cancer. Breast cancer is still the most frequent malignancy in women globally. However, the latest treatments, such as stem cell targeted therapy, are considered to be more effective in preventing recurrence, metastasis, and chemoresistance of breast cancer than older methods like chemotherapy and radiation. This review discusses the characteristics of stem cells and how stem cells may be used to treat breast cancer.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"324-333"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9399917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived <i>miR-27b- 3p</i> activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury.","authors":"Hongnan Li, Weidong Lin, Yunlei Li, Jiayang Zhang, Runsheng Liu, Minghai Qu, Ruihua Wang, Xiaomin Kang, Xuekun Xing","doi":"10.2174/1574888X19666230901140628","DOIUrl":"10.2174/1574888X19666230901140628","url":null,"abstract":"<p><strong>Background: </strong>To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and <i>miR-27</i> (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI).</p><p><strong>Approaches and results: </strong>We constructed a HIRI mouse model and pretreated it with an injection of agomir-<i>miR-27-3p</i>, agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+<i>miR-27b</i> mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with <i>miR-27</i> were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a <i>miR-27</i> target gene. Furthermore, compared to HIRI+NC mice, HIRI+<i>miR-27</i> mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, β-catenin, c-Myc, and Cyclin D1.</p><p><strong>Conclusion: </strong>Our findings reveal the role and mechanism of <i>miR-27</i> in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with <i>antimiR- 27</i> might demonstrate better protection against HIRI.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"755-766"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanan Fouad, Ibrahim A Albahlol, Hazim A Wahab, Eman H Nadwa, Heba M Galal, Mohamed Abouelkheir, Ahmed E Taha, Abdelkarim G Kamel, Hassan A Abdelmawlla
{"title":"Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.","authors":"Hanan Fouad, Ibrahim A Albahlol, Hazim A Wahab, Eman H Nadwa, Heba M Galal, Mohamed Abouelkheir, Ahmed E Taha, Abdelkarim G Kamel, Hassan A Abdelmawlla","doi":"10.2174/1574888X18666230713121530","DOIUrl":"10.2174/1574888X18666230713121530","url":null,"abstract":"<p><strong>Background: </strong>Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis.</p><p><strong>Objectives: </strong>The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage.</p><p><strong>Methods: </strong>Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (10<sup>6</sup> cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted.</p><p><strong>Results: </strong>BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs.</p><p><strong>Conclusion: </strong>The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"725-734"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9832285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faeze Shahedi, Arron Munggela Foma, Azam Mahmoudi-Aznaveh, Mohammad Ali Mazlomi, Zahra Azizi, Mohammad Reza Khorramizadeh
{"title":"Differentiation of Pancreatic Beta Cells: Dual Acting of Inflammatory Factors.","authors":"Faeze Shahedi, Arron Munggela Foma, Azam Mahmoudi-Aznaveh, Mohammad Ali Mazlomi, Zahra Azizi, Mohammad Reza Khorramizadeh","doi":"10.2174/1574888X18666230504093649","DOIUrl":"10.2174/1574888X18666230504093649","url":null,"abstract":"<p><p>In the past decades, scientists have made outstanding efforts to treat diabetes. However, diabetes treatment is still far from satisfactory due to the complex nature of the disease and the challenges encountered in resolving it. Inflammatory factors are key regulators of the immune system's response to pathological insults, organ neogenesis, rejuvenation of novel cells to replace injured cells and overwhelming disease conditions. Currently, the available treatments for type 1 diabetes include daily insulin injection, pancreatic beta cell or tissue transplantation, and gene therapy. Cell therapy, exploiting differentiation, and reprogramming various types of cells to generate pancreatic insulin-producing cells are novel approaches for the treatment of type 1 diabetes. A better understanding of the inflammatory pathways offers valuable and improved therapeutic options to provide more advanced and better treatments for diabetes. In this review, we investigated different types of inflammatory factors that participate in the pathogenesis of type 1 diabetes, their possible dual impacts on the differentiation, reprogramming, and fusion of other stem cell lines into pancreatic insulin-producing beta cells, and the possibility of applying these factors to improve the treatment of this disease.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"832-839"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9418175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}