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1
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Pulat S, Paguiri JAG, Gamage CDB, Varlı M, Zhou R, Park SY, Hur JS, Kim H. Lobaric acid suppresses the stemness potential of colorectal cancer cells through mTOR/AKT. Biofactors 2025; 51:e70002. [PMID: 39874220 DOI: 10.1002/biof.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 01/16/2025] [Indexed: 01/30/2025]
Abstract
Stereocaulon alpinum has been found to have potential pharmaceutical properties due to the presence of secondary metabolites such as usnic acid, atranorin, and lobaric acid (LA) which have anticancer activity. On the other hand, the effect of LA on the stemness potential of colorectal cancer (CRC) cells remains unexplored, and has not yet been thoroughly investigated. In this study, we examined the inhibitory activity of LA from Stereocaulon alpinum against the stemness potential of CRC cells and investigated the possible underlying mechanisms. The results demonstrated that LA did not inhibit the cell viability of CSC221 and DLD1. In addition, LA significantly decreased the spheroid formation of CSC221 and DLD1. Moreover, LA treatment suppressed cancer stem cell (CSC) markers; aldehyde dehydrogenase 1 (ALDH1), B-cell-specific Moloney leukemia virus insertion site 1 (BMI1), musashi1 (MSI1), and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), along with the sonic hedgehog (Shh) and mTOR/AKT pathways that contribute significantly to maintaining the stemness of CRC cells. Therefore, LA may be a new therapeutic approach for reducing the stemness of CRC cells.
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Affiliation(s)
- Sultan Pulat
- College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea
| | | | | | - Mücahit Varlı
- College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea
| | - Rui Zhou
- College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea
| | - So-Yeon Park
- College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea
| | - Jae-Seoun Hur
- Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea
| | - Hangun Kim
- College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea
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2
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Wang S, He Q, Qu Y, Yin W, Zhao R, Wang X, Yang Y, Guo ZN. Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy. Neural Regen Res 2024; 19:2430-2443. [PMID: 38526280 PMCID: PMC11090435 DOI: 10.4103/1673-5374.391313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/26/2023] [Accepted: 11/10/2023] [Indexed: 03/26/2024] Open
Abstract
Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
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Affiliation(s)
- Siji Wang
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Qianyan He
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yang Qu
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Wenjing Yin
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Ruoyu Zhao
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Xuyutian Wang
- Department of Breast Surgery, General Surgery Center, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yi Yang
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
- Neuroscience Research Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Zhen-Ni Guo
- Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
- Neuroscience Research Center, Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China
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3
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Meretsky CR, Polychronis A, Schiuma AT. A Comparative Analysis of the Advances in Stem Cell Therapy in Plastic Surgery: A Systematic Review of Current Applications and Future Directions. Cureus 2024; 16:e67067. [PMID: 39286681 PMCID: PMC11404395 DOI: 10.7759/cureus.67067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/17/2024] [Indexed: 09/19/2024] Open
Abstract
Stem cell (SC) therapy is revolutionizing the field of plastic surgery by harnessing the regenerative abilities of SCs derived from adipose tissue and bone marrow to boost tissue repair and enhance aesthetic outcomes. This groundbreaking method enhances results in procedures such as fat grafting, facial rejuvenation, and wound healing. As studies advance, SC therapy shows potential for more sophisticated uses in both reconstructive and cosmetic surgery. The objective of this review is to comprehensively examine the advances in SC therapy within the field of plastic surgery, highlighting its current applications and exploring future directions. The systematic review was conducted on SC therapy in plastic surgery adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and specific search criteria. This systematic review highlights these main outcomes, and SC therapy in plastic surgery enhances tissue repair and aesthetic outcomes by utilizing mesenchymal SCs such as adipose-derived SCs (ADSCs) and bone marrow-derived SCs (BMSCs), with platelet-rich plasma (PRP) providing additional support. Techniques such as scaffolds and cellular reprogramming are employed to guide SC growth, enabling tailored tissue engineering for complex regenerative procedures. This innovative approach accelerates healing, reduces scarring in reconstructive surgeries, improves skin texture, and ensures the natural integration of treated areas, ultimately yielding enhanced aesthetic results and transforming facial rejuvenation processes. SC therapy in plastic surgery holds great promise, but challenges such as protocol standardization, cost, and regulations still need to be addressed. SC therapy is leading innovative advancements in plastic surgery, offering superior outcomes and improved quality of life for patients. Interestingly, the future of plastic surgery is focused on integrating SC therapy for personalized and transformative treatments. Furthermore, interdisciplinary collaboration among bioengineers, clinicians, and regulatory bodies is essential for overcoming challenges and advancing SC research into clinical practice.
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Affiliation(s)
| | - Andreas Polychronis
- General Surgery, St. George's University School of Medicine, Great River, USA
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Cho YW, Yoon J, Song SG, Noh YW. Mitochondrial DNA as a target for analyzing the biodistribution of cell therapy products. Sci Rep 2024; 14:7934. [PMID: 38575614 PMCID: PMC10995129 DOI: 10.1038/s41598-024-56591-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Accepted: 03/08/2024] [Indexed: 04/06/2024] Open
Abstract
Biodistribution tests are crucial for evaluating the safety of cell therapy (CT) products in order to prevent unwanted organ homing of these products in patients. Quantitative polymerase chain reaction (qPCR) using intronic Alu is a popular method for biodistribution testing owing to its ability to detect donor cells without modifying CT products and low detection limit. However, Alu-qPCR may generate inaccurate information owing to background signals caused by the mixing of human genomic DNA with that of experimental animals. The aim of this study was to develop a test method that is more specific and sensitive than Alu-qPCR, targeting the mitochondrial DNA (mtDNA) sequence that varies substantially between humans and experimental animals. We designed primers for 12S, 16S, and cytochrome B in mtDNA regions, assessed their specificity and sensitivity, and selected primers and probes for the 12S region. Human adipose-derived stem cells, used as CT products, were injected into the tail vein of athymic NCr-nu/nu mice and detected, 7 d after administration, in their lungs at an average concentration of 2.22 ± 0.69 pg/μg mouse DNA, whereas Alu was not detected. Therefore, mtDNA is more specific and sensitive than Alu and is a useful target for evaluating CT product biodistribution.
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Affiliation(s)
- Young-Woo Cho
- College of Pharmacy, Chungbuk National University, Cheongju, 28644, Republic of Korea
- Division of Drug Screening Evaluation, NDDC, Osong Medical Innovation Foundation, Cheongju, 28160, Republic of Korea
| | - Jaehyeon Yoon
- Division of Drug Screening Evaluation, NDDC, Osong Medical Innovation Foundation, Cheongju, 28160, Republic of Korea
| | - Suk-Gil Song
- College of Pharmacy, Chungbuk National University, Cheongju, 28644, Republic of Korea.
| | - Young-Woock Noh
- Division of Drug Screening Evaluation, NDDC, Osong Medical Innovation Foundation, Cheongju, 28160, Republic of Korea.
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Fernández-Garza LE, Barrera-Barrera SA, Barrera-Saldaña HA. Mesenchymal Stem Cell Therapies Approved by Regulatory Agencies around the World. Pharmaceuticals (Basel) 2023; 16:1334. [PMID: 37765141 PMCID: PMC10536665 DOI: 10.3390/ph16091334] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 07/02/2023] [Accepted: 07/07/2023] [Indexed: 09/29/2023] Open
Abstract
Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels.
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Affiliation(s)
- Luis E. Fernández-Garza
- Laboratorio Nacional de Servicios Especializados de Investigación, Desarrollo e Innovación de Farmoquímicos y Biotecnológicos (LANSEIDI) del CONACyT, Sede Innbiogem SC, Monterrey 64630, Mexico; (L.E.F.-G.); (S.A.B.-B.)
- Departamento de Medicina Interna, Hospital General de Zona con Medicina Familiar No. 2 del Instituto Nacional del Seguro Social, Monterrey 64010, Mexico
| | - Silvia A. Barrera-Barrera
- Laboratorio Nacional de Servicios Especializados de Investigación, Desarrollo e Innovación de Farmoquímicos y Biotecnológicos (LANSEIDI) del CONACyT, Sede Innbiogem SC, Monterrey 64630, Mexico; (L.E.F.-G.); (S.A.B.-B.)
| | - Hugo A. Barrera-Saldaña
- Laboratorio Nacional de Servicios Especializados de Investigación, Desarrollo e Innovación de Farmoquímicos y Biotecnológicos (LANSEIDI) del CONACyT, Sede Innbiogem SC, Monterrey 64630, Mexico; (L.E.F.-G.); (S.A.B.-B.)
- Facultades de Medicina y Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66455, Mexico
- Columbia Investigación Científica, Panzacola 62, Colonia Villa Coyoacán, Alcaldía Coyoacán, Ciudad de Mexico 04010, Mexico
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Dynamic MRI of the Mesenchymal Stem Cells Distribution during Intravenous Transplantation in a Rat Model of Ischemic Stroke. Life (Basel) 2023; 13:life13020288. [PMID: 36836645 PMCID: PMC9962901 DOI: 10.3390/life13020288] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/29/2022] [Accepted: 01/17/2023] [Indexed: 01/22/2023] Open
Abstract
Systemic transplantation of mesenchymal stem cells (MSCs) is a promising approach for the treatment of ischemia-associated disorders, including stroke. However, exact mechanisms underlying its beneficial effects are still debated. In this respect, studies of the transplanted cells distribution and homing are indispensable. We proposed an MRI protocol which allowed us to estimate the dynamic distribution of single superparamagnetic iron oxide labeled MSCs in live ischemic rat brain during intravenous transplantation after the transient middle cerebral artery occlusion. Additionally, we evaluated therapeutic efficacy of cell therapy in this rat stroke model. According to the dynamic MRI data, limited numbers of MSCs accumulated diffusely in the brain vessels starting at the 7th minute from the onset of infusion, reached its maximum by 29 min, and gradually eliminated from cerebral circulation during 24 h. Despite low numbers of cells entering brain blood flow and their short-term engraftment, MSCs transplantation induced long lasting improvement of the neurological deficit, but without acceleration of the stroke volume reduction compared to the control animals during 14 post-transplantation days. Taken together, these findings indicate that MSCs convey their positive action by triggering certain paracrine mechanisms or cell-cell interactions or invoking direct long-lasting effects on brain vessels.
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Mohd Satar A, Othman FA, Tan SC. Biomaterial application strategies to enhance stem cell-based therapy for ischemic stroke. World J Stem Cells 2022; 14:851-867. [PMID: 36619694 PMCID: PMC9813837 DOI: 10.4252/wjsc.v14.i12.851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/29/2022] [Accepted: 12/06/2022] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Ischemic stroke is a condition in which an occluded blood vessel interrupts blood flow to the brain and causes irreversible neuronal cell death. Transplantation of regenerative stem cells has been proposed as a novel therapy to restore damaged neural circuitry after ischemic stroke attack. However, limitations such as low cell survival rates after transplantation remain significant challenges to stem cell-based therapy for ischemic stroke in the clinical setting. In order to enhance the therapeutic efficacy of transplanted stem cells, several biomaterials have been developed to provide a supportable cellular microenvironment or functional modification on the stem cells to optimize their reparative roles in injured tissues or organs. AIM To discuss state-of-the-art functional biomaterials that could enhance the therapeutic potential of stem cell-based treatment for ischemic stroke and provide detailed insights into the mechanisms underlying these biomaterial approaches. METHODS The PubMed, Science Direct and Scopus literature databases were searched using the keywords of "biomaterial" and "ischemic stroke". All topically-relevant articles were then screened to identify those with focused relevance to in vivo, in vitro and clinical studies related to "stem cells" OR "progenitor cells" OR "undifferentiated cells" published in English during the years of 2011 to 2022. The systematic search was conducted up to September 30, 2022. RESULTS A total of 19 articles matched all the inclusion criteria. The data contained within this collection of papers comprehensively represented 19 types of biomaterials applied on seven different types of stem/progenitor cells, namely mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, neural progenitor cells, endothelial progenitor cells, neuroepithelial progenitor cells, and neuroblasts. The potential major benefits gained from the application of biomaterials in stem cell-based therapy were noted as induction of structural and functional modifications, increased stem cell retention rate in the hostile ischemic microenvironment, and promoting the secretion of important cytokines for reparative mechanisms. CONCLUSION Biomaterials have a relatively high potential for enhancing stem cell therapy. Nonetheless, there is a scarcity of evidence from human clinical studies for the efficacy of this bioengineered cell therapy, highlighting that it is still too early to draw a definitive conclusion on efficacy and safety for patient usage. Future in-depth clinical investigations are necessary to realize translation of this therapy into a more conscientious and judicious evidence-based therapy for clinical application.
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Affiliation(s)
- Asmaa' Mohd Satar
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Farah Amna Othman
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Suat Cheng Tan
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia.
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Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice. Sci Rep 2022; 12:15646. [PMID: 36123386 PMCID: PMC9485227 DOI: 10.1038/s41598-022-19953-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 09/07/2022] [Indexed: 11/11/2022] Open
Abstract
Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasive imaging of cell trafficking offers such a potential. Herein, we evaluated and compared three different ready-to-use direct cell radiolabeling synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA for PET imaging-based trafficking of white blood cells (WBCs) and stem cells (SCs) up to 7 days in athymic nude mice. We compared the degree of 89Zr complexation and percentage of cell radiolabeling efficiencies with each. All three synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA, were successfully prepared, and used for radiolabeling of WBCs and SCs. The highest cell radiolabeling yield was found for [89Zr]Zr-DFO-Bn-NCS, followed by [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA. In terms of biodistribution, WBCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS, were primarily accumulated in liver and spleen, whereas SCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS were found in lung, liver and spleen. A high bone uptake was observed for both WBCs and SCs radiolabeled with [89Zr]Zr-Hy3ADA5-SA, suggesting in-vivo instability of [89Zr]Zr-Hy3ADA5-SA synthon. This study offers an appropriate selection of ready-to-use radiolabeling synthons for noninvasive trafficking of WBCs, SCs and other cell-based therapies.
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Optical molecular imaging and theranostics in neurological diseases based on aggregation-induced emission luminogens. Eur J Nucl Med Mol Imaging 2022; 49:4529-4550. [PMID: 35781601 PMCID: PMC9606072 DOI: 10.1007/s00259-022-05894-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 06/25/2022] [Indexed: 11/17/2022]
Abstract
Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further applied for molecular imaging and image-guided theranostics in neurological diseases such as cerebrovascular disease, neurodegenerative disease, and brain tumor, which help us understand more about the pathophysiological state of brain through noninvasive optical imaging approaches. Herein, we focus on representative AIEgens investigated on brain vasculature imaging and theranostics in neurological diseases including cerebrovascular disease, neurodegenerative disease, and brain tumor. Considering different imaging modalities and various therapeutic functions, AIEgens have great potential to broaden neurological research and meet urgent needs in clinical practice. It will be inspiring to develop more practical and versatile AIEgens as molecular imaging agents for preclinical and clinical use on neurological diseases.
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Optimization of Multimodal Nanoparticles Internalization Process in Mesenchymal Stem Cells for Cell Therapy Studies. Pharmaceutics 2022; 14:pharmaceutics14061249. [PMID: 35745821 PMCID: PMC9227698 DOI: 10.3390/pharmaceutics14061249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 06/06/2022] [Accepted: 06/09/2022] [Indexed: 11/17/2022] Open
Abstract
Considering there are several difficulties and limitations in labeling stem cells using multifunctional nanoparticles (MFNP), the purpose of this study was to determine the optimal conditions for labeling human bone marrow mesenchymal stem cells (hBM-MSC), aiming to monitor these cells in vivo. Thus, this study provides information on hBM-MSC direct labeling using multimodal nanoparticles in terms of concentration, magnetic field, and period of incubation while maintaining these cells’ viability and the homing ability for in vivo experiments. The cell labeling process was assessed using 10, 30, and 50 µg Fe/mL of MFNP, with periods of incubation ranging from 4 to 24 h, with or without a magnetic field, using optical microscopy, near-infrared fluorescence (NIRF), and inductively coupled plasma mass spectrometry (ICP-MS). After the determination of optimal labeling conditions, these cells were applied in vivo 24 h after stroke induction, intending to evaluate cell homing and improve NIRF signal detection. In the presence of a magnetic field and utilizing the maximal concentration of MFNP during cell labeling, the iron load assessed by NIRF and ICP-MS was four times higher than what was achieved before. In addition, considering cell viability higher than 98%, the recommended incubation time was 9 h, which corresponded to a 25.4 pg Fe/cell iron load (86% of the iron load internalized in 24 h). The optimization of cellular labeling for application in the in vivo study promoted an increase in the NIRF signal by 215% at 1 h and 201% at 7 h due to the use of a magnetized field during the cellular labeling process. In the case of BLI, the signal does not depend on cell labeling showing no significant differences between unlabeled or labeled cells (with or without a magnetic field). Therefore, the in vitro cellular optimized labeling process using magnetic fields resulted in a shorter period of incubation with efficient iron load internalization using higher MFNP concentration (50 μgFe/mL), leading to significant improvement in cell detection by NIRF technique without compromising cellular viability in the stroke model.
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Nigam S, Bishop JO, Hayat H, Quadri T, Hayat H, Wang P. Nanotechnology in Immunotherapy for Type 1 Diabetes: Promising Innovations and Future Advances. Pharmaceutics 2022; 14:644. [PMID: 35336018 PMCID: PMC8955746 DOI: 10.3390/pharmaceutics14030644] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetes is a chronic condition which affects the glucose metabolism in the body. In lieu of any clinical "cure," the condition is managed through the administration of pharmacological aids, insulin supplements, diet restrictions, exercise, and the like. The conventional clinical prescriptions are limited by their life-long dependency and diminished potency, which in turn hinder the patient's recovery. This necessitated an alteration in approach and has instigated several investigations into other strategies. As Type 1 diabetes (T1D) is known to be an autoimmune disorder, targeting the immune system in activation and/or suppression has shown promise in reducing beta cell loss and improving insulin levels in response to hyperglycemia. Another strategy currently being explored is the use of nanoparticles in the delivery of immunomodulators, insulin, or engineered vaccines to endogenous immune cells. Nanoparticle-assisted targeting of immune cells holds substantial potential for enhanced patient care within T1D clinical settings. Herein, we summarize the knowledge of etiology, clinical scenarios, and the current state of nanoparticle-based immunotherapeutic approaches for Type 1 diabetes. We also discuss the feasibility of translating this approach to clinical practice.
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Affiliation(s)
- Saumya Nigam
- Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; (S.N.); (J.O.B.); (H.H.); (T.Q.); (H.H.)
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - Jack Owen Bishop
- Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; (S.N.); (J.O.B.); (H.H.); (T.Q.); (H.H.)
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - Hanaan Hayat
- Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; (S.N.); (J.O.B.); (H.H.); (T.Q.); (H.H.)
- Lyman Briggs College, Michigan State University, East Lansing, MI 48824, USA
| | - Tahnia Quadri
- Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; (S.N.); (J.O.B.); (H.H.); (T.Q.); (H.H.)
- Lyman Briggs College, Michigan State University, East Lansing, MI 48824, USA
| | - Hasaan Hayat
- Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; (S.N.); (J.O.B.); (H.H.); (T.Q.); (H.H.)
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - Ping Wang
- Precision Health Program, Michigan State University, East Lansing, MI 48824, USA; (S.N.); (J.O.B.); (H.H.); (T.Q.); (H.H.)
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
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Hariharan A, Iyer J, Wang A, Tran SD. Tracking of Oral and Craniofacial Stem Cells in Tissue Development, Regeneration, and Diseases. Curr Osteoporos Rep 2021; 19:656-668. [PMID: 34741728 DOI: 10.1007/s11914-021-00705-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/15/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE OF REVIEW The craniofacial region hosts a variety of stem cells, all isolated from different sources of bone and cartilage. However, despite scientific advancements, their role in tissue development and regeneration is not entirely understood. The goal of this review is to discuss recent advances in stem cell tracking methods and how these can be advantageously used to understand oro-facial tissue development and regeneration. RECENT FINDINGS Stem cell tracking methods have gained importance in recent times, mainly with the introduction of several molecular imaging techniques, like optical imaging, computed tomography, magnetic resonance imaging, and ultrasound. Labelling of stem cells, assisted by these imaging techniques, has proven to be useful in establishing stem cell lineage for regenerative therapy of the oro-facial tissue complex. Novel labelling methods complementing imaging techniques have been pivotal in understanding craniofacial tissue development and regeneration. These stem cell tracking methods have the potential to facilitate the development of innovative cell-based therapies.
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Affiliation(s)
- Arvind Hariharan
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Janaki Iyer
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Athena Wang
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Simon D Tran
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada.
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Sun H, Wang Y, Wang Y, Ji F, Wang A, Yang M, He X, Li L. Bivalent Regulation and Related Mechanisms of H3K4/27/9me3 in Stem Cells. Stem Cell Rev Rep 2021; 18:165-178. [PMID: 34417934 DOI: 10.1007/s12015-021-10234-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2021] [Indexed: 12/24/2022]
Abstract
The "bivalent domain" is a unique histone modification region consisting of two histone tri-methylation modifications. Over the years, it has been revealed that the maintenance and dynamic changes of the bivalent domains play a vital regulatory role in the differentiation of various stem cell systems, as well as in other cells, such as immunomodulation. Tri-methylation modifications involved in the formation of the bivalent domains are interrelated and mutually regulated, thus regulating many life processes of cells. Tri-methylation of histone H3 at lysine 4 (H3K4me3), tri-methylation of histone H3 at lysine 9 (H3K9me3) and tri-methylation of histone H3 at lysine 27 (H3K27me3) are the main tri-methylation modifications involved in the formation of bivalent domains. The three form different bivalent domains in pairs. Furthermore, it is equally clear that H3K4me3 is a positive regulator of transcription and that H3K9me3/H3K27me3 are negative regulators. Enzymes related to the regulation of histone methylation play a significant role in the "homeostasis" and "breaking homeostasis" of the bivalent domains. Bivalent domains regulate target genes, upstream transcription, downstream targeting regulation and related cytokines during the establishment and breakdown of homeostasis, and exert the specific regulation of stem cells. Indeed, a unified mechanism to explain the bivalent modification in all stem cells has been difficult to define, and whether the bivalent modification is antagonistic in inducing the differentiation of homologous stem cells is controversial. In this review, we focus on the different bivalent modifications in several key stem cells and explore the main mechanisms and effects of these modifications involved. Finally, we discussed the close relationship between bivalent domains and immune cells, and put forward the prospect of the application of bivalent domains in the field of stem cells.
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Affiliation(s)
- Han Sun
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China
| | - Yin Wang
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China
| | - Ying Wang
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China
| | - Feng Ji
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China
| | - An Wang
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China
| | - Ming Yang
- Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
| | - Xu He
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
| | - Lisha Li
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
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The Implementation of Preconditioned Epidermal Neural Crest Stem Cells to Combat Ischemic Stroke. Comment on Othman, F.A.; Tan, S.C. Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke. Brain Sci. 2020, 10, 893. Brain Sci 2021; 11:brainsci11050653. [PMID: 34067592 PMCID: PMC8155980 DOI: 10.3390/brainsci11050653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/07/2021] [Accepted: 05/13/2021] [Indexed: 12/24/2022] Open
Abstract
In the recent review published in Brain Sciences, Othman and Tan suggested several preconditioning strategies to improve stem cell therapy after ischemic brain injury [...].
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