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Goyal P, Malviya R. Stem Cell Therapy for the Management of Type 1 Diabetes: Advances and Perspectives. Endocr Metab Immune Disord Drug Targets 2024; 24:549-561. [PMID: 37861029 DOI: 10.2174/0118715303256582230919093535] [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] [Received: 04/05/2023] [Revised: 07/20/2023] [Accepted: 08/25/2023] [Indexed: 10/21/2023]
Abstract
Due to insulin resistance and excessive blood sugar levels, type 1 diabetes mellitus (T1DM) is characterized by pancreatic cell loss. This condition affects young people at a higher rate than any other chronic autoimmune disease. Regardless of the method, exogenous insulin cannot substitute for insulin produced by a healthy pancreas. An emerging area of medicine is pancreatic and islet transplantation for type 1 diabetics to restore normal blood sugar regulation. However, there are still obstacles standing in the way of the widespread use of these therapies, including very low availability of pancreatic and islets supplied from human organ donors, challenging transplantation conditions, high expenses, and a lack of easily accessible methods. Efforts to improve Type 1 Diabetes treatment have been conducted in response to the disease's increasing prevalence. Type 1 diabetes may one day be treated with stem cell treatment. Stem cell therapy has proven to be an effective treatment for type 1 diabetes. Recent progress in stem cell-based diabetes treatment is summarised, and the authors show how to isolate insulin-producing cells (IPCs) from a variety of progenitor cells.
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Affiliation(s)
- Priyanshi Goyal
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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2
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Baker S, Gilhen-Baker M, Roviello GN. The Role of Nutrition and Forest-Bathing in the Physical Rehabilitation of Physically Inactive Patients: From the Molecular Aspects to New Nature-Inspired Techniques. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 20:793. [PMID: 36613115 PMCID: PMC9819495 DOI: 10.3390/ijerph20010793] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 12/19/2022] [Accepted: 12/26/2022] [Indexed: 05/07/2023]
Abstract
Physical rehabilitation plays a fundamental role in the management of individuals with disabilities associated with age-related muscle loss or affected by catastrophic conditions such as trauma, surgery, cancer or other severe pathologies. These events have in common an extended period of physical inactivity. Patients who undergo prolonged bed rest often present with a number of complications; for example, muscle loss that can exacerbate existing conditions determined by sarcopenia, which in turn greatly limits physical functions. The main scope of this work is to summarize certain key strategies for the physiotherapeutic management of physically inactive patients, regardless of the reason behind their prolonged bed rest, with a particular focus on physical rehabilitation, nutrition and forest-bathing. The importance of correct nutrition in counter-acting the loss of muscle mass and consequent function is explored alongside a description of the main nutrients that are needed for muscle regeneration. From a biomolecular perspective, some specific molecular mechanisms associated with physical rehabilitation are also reported not only in the context of physical therapy, but also within nature-inspired techniques, such as forest-bathing as well as body self-healing. Combining a targeted physiotherapeutic approach with an appropriate diet as well as nature-based therapy could thus help with the recovery of bed ridden patients.
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Affiliation(s)
- Steven Baker
- Compete Physiotherapy and Rehabilitation Centre, Unit 1 Bridge Mill—Cowan Bridge, Carnforth LA6 2HS, UK
| | | | - Giovanni N. Roviello
- Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Area di Ricerca Site and Headquarters, Via Pietro Castellino 111, 80131 Naples, Italy
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3
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Mayani H, Chávez-González A, Vázquez-Santillan K, Contreras J, Guzman ML. Cancer Stem Cells: Biology and Therapeutic Implications. Arch Med Res 2022; 53:770-784. [PMID: 36462951 DOI: 10.1016/j.arcmed.2022.11.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/14/2022] [Accepted: 11/22/2022] [Indexed: 12/05/2022]
Abstract
It is well recognized that most cancers derive and progress from transformation and clonal expansion of a single cell that possesses stem cell properties, i.e., self-renewal and multilineage differentiation capacities. Such cancer stem cells (CSCs) are usually present at very low frequencies and possess properties that make them key players in tumor development. Indeed, besides having the ability to initiate tumor growth, CSCs drive tumor progression and metastatic dissemination, are resistant to most cancer drugs, and are responsible for cancer relapse. All of these features make CSCs attractive targets for the development of more effective oncologic treatments. In the present review article, we have summarized recent advances in the biology of CSCs, including their identification through their immunophenotype, and their physiology, both in vivo and in vitro. We have also analyzed some molecular markers that might become targets for developing new therapies aiming at hampering CSCs regeneration and cancer relapse.
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Affiliation(s)
- Hector Mayani
- Unidad de Investigaci..n en Enfermedades Oncol..gicas, Hospital de Oncolog.ía, Centro M..dico Nacional SXXI, Instituto Mexicano del Seguro Social. Ciudad de M..xico, M..xico.
| | - Antonieta Chávez-González
- Unidad de Investigaci..n en Enfermedades Oncol..gicas, Hospital de Oncolog.ía, Centro M..dico Nacional SXXI, Instituto Mexicano del Seguro Social. Ciudad de M..xico, M..xico
| | | | - Jorge Contreras
- Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Monica L Guzman
- Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY, USA
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Rinkevich B, Ballarin L, Martinez P, Somorjai I, Ben‐Hamo O, Borisenko I, Berezikov E, Ereskovsky A, Gazave E, Khnykin D, Manni L, Petukhova O, Rosner A, Röttinger E, Spagnuolo A, Sugni M, Tiozzo S, Hobmayer B. A pan-metazoan concept for adult stem cells: the wobbling Penrose landscape. Biol Rev Camb Philos Soc 2022; 97:299-325. [PMID: 34617397 PMCID: PMC9292022 DOI: 10.1111/brv.12801] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/17/2022]
Abstract
Adult stem cells (ASCs) in vertebrates and model invertebrates (e.g. Drosophila melanogaster) are typically long-lived, lineage-restricted, clonogenic and quiescent cells with somatic descendants and tissue/organ-restricted activities. Such ASCs are mostly rare, morphologically undifferentiated, and undergo asymmetric cell division. Characterized by 'stemness' gene expression, they can regulate tissue/organ homeostasis, repair and regeneration. By contrast, analysis of other animal phyla shows that ASCs emerge at different life stages, present both differentiated and undifferentiated phenotypes, and may possess amoeboid movement. Usually pluri/totipotent, they may express germ-cell markers, but often lack germ-line sequestering, and typically do not reside in discrete niches. ASCs may constitute up to 40% of animal cells, and participate in a range of biological phenomena, from whole-body regeneration, dormancy, and agametic asexual reproduction, to indeterminate growth. They are considered legitimate units of selection. Conceptualizing this divergence, we present an alternative stemness metaphor to the Waddington landscape: the 'wobbling Penrose' landscape. Here, totipotent ASCs adopt ascending/descending courses of an 'Escherian stairwell', in a lifelong totipotency pathway. ASCs may also travel along lower stemness echelons to reach fully differentiated states. However, from any starting state, cells can change their stemness status, underscoring their dynamic cellular potencies. Thus, vertebrate ASCs may reflect just one metazoan ASC archetype.
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Affiliation(s)
- Baruch Rinkevich
- Israel Oceanographic & Limnological ResearchNational Institute of OceanographyPOB 9753, Tel ShikmonaHaifa3109701Israel
| | - Loriano Ballarin
- Department of BiologyUniversity of PadovaVia Ugo Bassi 58/BPadova35121Italy
| | - Pedro Martinez
- Departament de Genètica, Microbiologia i EstadísticaUniversitat de BarcelonaAv. Diagonal 643Barcelona08028Spain
- Institut Català de Recerca i Estudis Avançats (ICREA)Passeig Lluís Companys 23Barcelona08010Spain
| | - Ildiko Somorjai
- School of BiologyUniversity of St AndrewsSt Andrews, FifeKY16 9ST, ScotlandUK
| | - Oshrat Ben‐Hamo
- Israel Oceanographic & Limnological ResearchNational Institute of OceanographyPOB 9753, Tel ShikmonaHaifa3109701Israel
| | - Ilya Borisenko
- Department of Embryology, Faculty of BiologySaint‐Petersburg State UniversityUniversity Embankment, 7/9Saint‐Petersburg199034Russia
| | - Eugene Berezikov
- European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center GroningenAntonius Deusinglaan 1Groningen9713 AVThe Netherlands
| | - Alexander Ereskovsky
- Department of Embryology, Faculty of BiologySaint‐Petersburg State UniversityUniversity Embankment, 7/9Saint‐Petersburg199034Russia
- Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Aix Marseille University, CNRS, IRD, Avignon UniversityJardin du Pharo, 58 Boulevard Charles LivonMarseille13007France
- Koltzov Institute of Developmental Biology of Russian Academy of SciencesUlitsa Vavilova, 26Moscow119334Russia
| | - Eve Gazave
- Université de Paris, CNRS, Institut Jacques MonodParisF‐75006France
| | - Denis Khnykin
- Department of PathologyOslo University HospitalBygg 19, Gaustad Sykehus, Sognsvannsveien 21Oslo0188Norway
| | - Lucia Manni
- Department of BiologyUniversity of PadovaVia Ugo Bassi 58/BPadova35121Italy
| | - Olga Petukhova
- Collection of Vertebrate Cell CulturesInstitute of Cytology, Russian Academy of SciencesTikhoretsky Ave. 4St. Petersburg194064Russia
| | - Amalia Rosner
- Israel Oceanographic & Limnological ResearchNational Institute of OceanographyPOB 9753, Tel ShikmonaHaifa3109701Israel
| | - Eric Röttinger
- Université Côte d'Azur, CNRS, INSERM, Institute for Research on Cancer and Aging, Nice (IRCAN)Nice06107France
- Université Côte d'Azur, Federative Research Institute – Marine Resources (IFR MARRES)28 Avenue de ValroseNice06103France
| | - Antonietta Spagnuolo
- Department of Biology and Evolution of Marine OrganismsStazione Zoologica Anton DohrnVilla ComunaleNaples80121Italy
| | - Michela Sugni
- Department of Environmental Science and Policy (ESP)Università degli Studi di MilanoVia Celoria 26Milan20133Italy
| | - Stefano Tiozzo
- Sorbonne Université, CNRS, Laboratoire de Biologie du Développement de Villefranche‐sur‐mer (LBDV)06234 Villefranche‐sur‐MerVillefranche sur MerCedexFrance
| | - Bert Hobmayer
- Institute of Zoology and Center for Molecular Biosciences, University of InnsbruckTechnikerstrInnsbruck256020Austria
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Yu H, Commander CW, Stavas JM. Stem Cell-Based Therapies: What Interventional Radiologists Need to Know. Semin Intervent Radiol 2021; 38:523-534. [PMID: 34853498 DOI: 10.1055/s-0041-1736657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
As the basic units of biological organization, stem cells and their progenitors are essential for developing and regenerating organs and tissue systems using their unique self-renewal capability and differentiation potential into multiple cell lineages. Stem cells are consistently present throughout the entire human development, from the zygote to adulthood. Over the past decades, significant efforts have been made in biology, genetics, and biotechnology to develop stem cell-based therapies using embryonic and adult autologous or allogeneic stem cells for diseases without therapies or difficult to treat. Stem cell-based therapies require optimum administration of stem cells into damaged organs to promote structural regeneration and improve function. Maximum clinical efficacy is highly dependent on the successful delivery of stem cells to the target tissue. Direct image-guided locoregional injections into target tissues offer an option to increase therapeutic outcomes. Interventional radiologists have the opportunity to perform a key role in delivering stem cells more efficiently using minimally invasive techniques. This review discusses the types and sources of stem cells and the current clinical applications of stem cell-based therapies. In addition, the regulatory considerations, logistics, and potential roles of interventional Radiology are also discussed with the review of the literature.
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Affiliation(s)
- Hyeon Yu
- Division of Vascular and Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.,ProKidney LLC, Winston Salem, North Carolina
| | - Clayton W Commander
- Division of Vascular and Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Joseph M Stavas
- Department of Radiology, Creighton University School of Medicine, Omaha, Nebraska
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Stevanovic M, Kovacevic-Grujicic N, Mojsin M, Milivojevic M, Drakulic D. SOX transcription factors and glioma stem cells: Choosing between stemness and differentiation. World J Stem Cells 2021; 13:1417-1445. [PMID: 34786152 PMCID: PMC8567447 DOI: 10.4252/wjsc.v13.i10.1417] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 07/15/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Glioblastoma (GBM) is the most common, most aggressive and deadliest brain tumor. Recently, remarkable progress has been made towards understanding the cellular and molecular biology of gliomas. GBM tumor initiation, progression and relapse as well as resistance to treatments are associated with glioma stem cells (GSCs). GSCs exhibit a high proliferation rate and self-renewal capacity and the ability to differentiate into diverse cell types, generating a range of distinct cell types within the tumor, leading to cellular heterogeneity. GBM tumors may contain different subsets of GSCs, and some of them may adopt a quiescent state that protects them against chemotherapy and radiotherapy. GSCs enriched in recurrent gliomas acquire more aggressive and therapy-resistant properties, making them more malignant, able to rapidly spread. The impact of SOX transcription factors (TFs) on brain tumors has been extensively studied in the last decade. Almost all SOX genes are expressed in GBM, and their expression levels are associated with patient prognosis and survival. Numerous SOX TFs are involved in the maintenance of the stemness of GSCs or play a role in the initiation of GSC differentiation. The fine-tuning of SOX gene expression levels controls the balance between cell stemness and differentiation. Therefore, innovative therapies targeting SOX TFs are emerging as promising tools for combatting GBM. Combatting GBM has been a demanding and challenging goal for decades. The current therapeutic strategies have not yet provided a cure for GBM and have only resulted in a slight improvement in patient survival. Novel approaches will require the fine adjustment of multimodal therapeutic strategies that simultaneously target numerous hallmarks of cancer cells to win the battle against GBM.
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Affiliation(s)
- Milena Stevanovic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
- Chair Biochemistry and Molecular Biology, Faculty of Biology, University of Belgrade, Belgrade 11158, Serbia
- Department of Chemical and Biological Sciences, Serbian Academy of Sciences and Arts, Belgrade 11000, Serbia.
| | - Natasa Kovacevic-Grujicic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
| | - Marija Mojsin
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
| | - Milena Milivojevic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
| | - Danijela Drakulic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
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7
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Stem Cells an Overview. Stem Cells 2021. [DOI: 10.1007/978-981-16-1638-9_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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8
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Liu L, Wu J, Gao Y, Lv Y, Xue J, Qin L, Xiao C, Hu Z, Zhang L, Luo X, Wang Y, Cao Y, Cao Y, Zhang G. The effect of Acot2 overexpression or downregulation on the preadipocyte differentiation in Chinese Red Steppe cattle. Adipocyte 2020; 9:279-289. [PMID: 32579860 PMCID: PMC7469445 DOI: 10.1080/21623945.2020.1776553] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
The quality and nutritional value of beef is closely linked to its content of intramuscular fat (IMF). The differentiation of preadipocytes and the deposition of lipid droplets in the adipocytes are the key to regulate the IMF content. The differentiation of adipocytes is regulated by a series of transcription factors and genes. Acyl-CoA thioesterase 2 (Acot2) hydrolyzes the acyl-coenzyme A (CoA) into free fatty acids and CoA and has the potential to maintain the free fatty acids and acyl CoA at the cellular level. In this work, we detected the expression of the Acot2 gene during the adipocyte differentiation in Chinese Red Steppe cattle, and then interfered and overexpressed the Acot2 gene in the preadipocytes to explore its regulatory role in the adipocyte differentiation. The results showed that the expression and regulation of Acot2 mainly occurred at the later stage of the adipocyte differentiation. The interference with the Acot2 gene significantly inhibited the lipid droplets accumulation and triglyceride content, while its overexpression significantly promoted both of them. The results of this study show that the Acot2 gene is a positive regulator of the adipocyte differentiation and may become a new target to improve the beef quality.
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Affiliation(s)
- Lixiang Liu
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Jian Wu
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
- Jilin Beef Cattle Breeding and Breeding Technology Innovation Center, Gongzhuling, China
- Jilin Kuncheng Animal Husbandry Technology Development Co., Ltd, Gongzhuling, China
| | - Yi Gao
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
| | - Yang Lv
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Jiajia Xue
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Lihong Qin
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
- Jilin Beef Cattle Breeding and Breeding Technology Innovation Center, Gongzhuling, China
| | - Cheng Xiao
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Zhongchang Hu
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Lichun Zhang
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Xiaotong Luo
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
| | - Yanli Wang
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
| | - Yang Cao
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Yang Cao
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
| | - Guoliang Zhang
- Branch of Animal Husbandry, Jilin Academy of Agricultural Science, Gongzhuling, China
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Beef Cattle Genetics and Breeding, Ministry of Agriculture and Rural Agriculture, Changchun, China
- Jilin Beef Cattle Breeding and Breeding Technology Innovation Center, Gongzhuling, China
- Jilin Kuncheng Animal Husbandry Technology Development Co., Ltd, Gongzhuling, China
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Duddu S, Chakrabarti R, Ghosh A, Shukla PC. Hematopoietic Stem Cell Transcription Factors in Cardiovascular Pathology. Front Genet 2020; 11:588602. [PMID: 33193725 PMCID: PMC7596349 DOI: 10.3389/fgene.2020.588602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022] Open
Abstract
Transcription factors as multifaceted modulators of gene expression that play a central role in cell proliferation, differentiation, lineage commitment, and disease progression. They interact among themselves and create complex spatiotemporal gene regulatory networks that modulate hematopoiesis, cardiogenesis, and conditional differentiation of hematopoietic stem cells into cells of cardiovascular lineage. Additionally, bone marrow-derived stem cells potentially contribute to the cardiovascular cell population and have shown potential as a therapeutic approach to treat cardiovascular diseases. However, the underlying regulatory mechanisms are currently debatable. This review focuses on some key transcription factors and associated epigenetic modifications that modulate the maintenance and differentiation of hematopoietic stem cells and cardiac progenitor cells. In addition to this, we aim to summarize different potential clinical therapeutic approaches in cardiac regeneration therapy and recent discoveries in stem cell-based transplantation.
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Affiliation(s)
| | | | | | - Praphulla Chandra Shukla
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
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Wang J, Sun M, Liu W, Li Y, Li M. Stem Cell-Based Therapies for Liver Diseases: An Overview and Update. Tissue Eng Regen Med 2019; 16:107-118. [PMID: 30989038 DOI: 10.1007/s13770-019-00178-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 01/04/2019] [Accepted: 01/08/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases. METHODS In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy. RESULTS Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells. In vitro and in vivo studies have demonstrated that stem cells are promising cell sources for the liver regeneration. CONCLUSION Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.
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Affiliation(s)
- Jie Wang
- 1Department of Neurology, The China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033 Jilin China
| | - Meiyan Sun
- Medical Examination College, Jilin Medical University, No. 5 Jilin Street, Changchun, Jilin, 132013 China
| | - Wei Liu
- Medical Examination College, Jilin Medical University, No. 5 Jilin Street, Changchun, Jilin, 132013 China
| | - Yan Li
- Medical Examination College, Jilin Medical University, No. 5 Jilin Street, Changchun, Jilin, 132013 China
| | - Miao Li
- 3Department of Neurosurgery, The China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033 China
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Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis. Stem Cells Int 2019; 2019:1726743. [PMID: 30719047 PMCID: PMC6335774 DOI: 10.1155/2019/1726743] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 10/30/2018] [Indexed: 12/16/2022] Open
Abstract
Granulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to explore whether pretreating BM-MSCs with G-CSF can promote their ability of homing to the lung after in vitro transplantation via upregulating the CXCR4 expression, potentially markedly increasing the antifibrotic effect of BM-MSCs. The BM-MSCs pretreated with G-CSF were transplanted into a mouse on day 14 after bleomycin injection. The antifibrotic effects of BM-MSCs in mice were tested on day 21 by using pathological examination and collagen content assay. Pretreatment of BM-MSCs with G-CSF significantly promoted their ability of homing to the lung and enhanced their antifibrotic effects. However, knocking down the CXCR4 expression in BM-MSCs significantly inhibited the ability of G-CSF to promote the migration and homing of BM-MSCs to the lung and the resulting antifibrotic effects. We also found that G-CSF significantly increased the CXCR4 expression and AKT phosphorylation in BM-MSCs, and the AKT pathway inhibitor LY294002 significantly diminished the ability of G-CSF to upregulate the CXCR4 expression in BM-MSCs. Pretreatment of BM-MSCs with G-CSF promotes the homing of BM-MSCs to the lung via upregulating the CXCR4 expression, leading to a marked increase in the antifibrotic effects of BM-MSCs. This study provides new avenues for the application of BM-MSCs in the repair of different tissues.
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Basoli V, Santaniello S, Cruciani S, Ginesu GC, Cossu ML, Delitala AP, Serra PA, Ventura C, Maioli M. Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells. Int J Mol Sci 2017; 18:981. [PMID: 28475114 PMCID: PMC5454894 DOI: 10.3390/ijms18050981] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 04/28/2017] [Accepted: 05/02/2017] [Indexed: 02/07/2023] Open
Abstract
Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor γ (PPAR-γ), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.
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Affiliation(s)
- Valentina Basoli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Via Massarenti, 40138 Bologna, Italy.
- Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, A-1190 Vienna, Austria.
| | - Sara Santaniello
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Via Massarenti, 40138 Bologna, Italy.
| | - Sara Cruciani
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, A-1190 Vienna, Austria.
| | - Giorgio Carlo Ginesu
- Clinical and Experimental Medicine Department, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
| | - Maria Laura Cossu
- Clinical and Experimental Medicine Department, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
| | | | - Pier Andrea Serra
- Clinical and Experimental Medicine Department, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
- Center for Developmental Biology and Reprogramming (CEDEBIOR), Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
| | - Carlo Ventura
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Via Massarenti, 40138 Bologna, Italy.
- Stem Wave Institute for Tissue Healing (SWITH), Gruppo VillaMaria and Ettore Sansavini Health Science Foundation, Via Provinciale per Cotignola 9, 48022 Lugo, Ravenna, Italy.
| | - Margherita Maioli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
- Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Via Massarenti, 40138 Bologna, Italy.
- Stem Wave Institute for Tissue Healing (SWITH), Gruppo VillaMaria and Ettore Sansavini Health Science Foundation, Via Provinciale per Cotignola 9, 48022 Lugo, Ravenna, Italy.
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
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Lo Furno D, Mannino G, Cardile V, Parenti R, Giuffrida R. Potential Therapeutic Applications of Adipose-Derived Mesenchymal Stem Cells. Stem Cells Dev 2016; 25:1615-1628. [PMID: 27520311 DOI: 10.1089/scd.2016.0135] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Stem cells are subdivided into two main categories: embryonic and adult stem cells. In principle, pluripotent embryonic stem cells might differentiate in any cell types of the organism, whereas the potential of adult stem cells would be more restricted. Although adult stem cells from bone marrow have been initially the most extensively studied, those derived from human adipose tissue have been lately more widely investigated, because of several advantages. First, they can be easily obtained in large amounts from subcutaneous adipose tissue, with minimal pain and morbidity for the patients during harvesting. In addition, they feature low immunogenicity and can differentiate not only in cells of mesodermal lineage (adipocytes, osteoblasts, chondrocytes and muscle cells), but also in cells of other germ layers, such as neural or epithelial cells. As their multilineage differentiation capabilities are increasingly highlighted, their possible use in cell-based regenerative medicine is now broadly explored. In fact, starting from in vitro observations, many studies have already entered the preclinical and clinical phases. In this review, because of our main scientific interest, adipogenic, osteogenic, chondrogenic, and neurogenic differentiation abilities of adipose-derived mesenchymal stem cells, as well as their possible therapeutic applications, are chiefly focused. In addition, their ability to differentiate toward muscle, epithelial, pancreatic, and hepatic cells is briefly reported.
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Affiliation(s)
- Debora Lo Furno
- Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania , Catania, Italy
| | - Giuliana Mannino
- Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania , Catania, Italy
| | - Venera Cardile
- Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania , Catania, Italy
| | - Rosalba Parenti
- Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania , Catania, Italy
| | - Rosario Giuffrida
- Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania , Catania, Italy
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Therapeutic Potential of Stem Cells Strategy for Cardiovascular Diseases. Stem Cells Int 2016; 2016:4285938. [PMID: 27829839 PMCID: PMC5088322 DOI: 10.1155/2016/4285938] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 08/09/2016] [Accepted: 09/20/2016] [Indexed: 02/06/2023] Open
Abstract
Despite development of medicine, cardiovascular diseases (CVDs) are still the leading cause of mortality and morbidity worldwide. Over the past 10 years, various stem cells have been utilized in therapeutic strategies for the treatment of CVDs. CVDs are characterized by a broad range of pathological reactions including inflammation, necrosis, hyperplasia, and hypertrophy. However, the causes of CVDs are still unclear. While there is a limit to the currently available target-dependent treatments, the therapeutic potential of stem cells is very attractive for the treatment of CVDs because of their paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. Various studies have recently reported increased therapeutic potential of transplantation of microRNA- (miRNA-) overexpressing stem cells or small-molecule-treated cells. In addition to treatment with drugs or overexpressed miRNA in stem cells, stem cell-derived extracellular vesicles also have therapeutic potential because they can deliver the stem cell-specific RNA and protein into the host cell, thereby improving cell viability. Here, we reported the state of stem cell-based therapy for the treatment of CVDs and the potential for cell-free based therapy.
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15
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G-CSF-mobilized Bone Marrow Mesenchymal Stem Cells Replenish Neural Lineages in Alzheimer's Disease Mice via CXCR4/SDF-1 Chemotaxis. Mol Neurobiol 2016; 54:6198-6212. [PMID: 27709493 DOI: 10.1007/s12035-016-0122-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Accepted: 09/12/2016] [Indexed: 10/20/2022]
Abstract
Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer's disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells. Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate into the brain, but only BM-MSCs replenished the neural lineage cells and contributed to neurogenesis in the brains of AD mice. Together, our data show that mobilized BM-MSCs are involved in the replenishment of neural lineages following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the potential use of BM-MSCs for further autogenically therapeutic applications.
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16
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Lucaciu O, Crisan B, Crisan L, Baciut M, Soritau O, Bran S, Biris AR, Hurubeanu L, Hedesiu M, Vacaras S, Kretschmer W, Dirzu N, Campian RS, Baciut G. In quest of optimal drug-supported and targeted bone regeneration in the cranio facial area: a review of techniques and methods. Drug Metab Rev 2016; 47:455-69. [PMID: 26689239 DOI: 10.3109/03602532.2015.1124889] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Craniofacial bone structures are frequently and extensively affected by trauma, tumors, bone infections and diseases, age-related degeneration and atrophy, as well as congenital malformations and developmental anomalies. Consequently, severe encumbrances are imposed on both patients and healthcare systems due to the complex and lengthy treatment duration. The search for alternative methods to bone transplantation, grafting and the use of homologous or heterologous bone thus responds to one of the most significant problems in human medicine. This review focuses on the current consensus of bone-tissue engineering in the craniofacial area with emphasis on drug-induced stem cell differentiation and induced bone regeneration.
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Affiliation(s)
- Ondine Lucaciu
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Bogdan Crisan
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Liana Crisan
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Mihaela Baciut
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Olga Soritau
- b "Ion Chiricuta" Oncological Institute , Cluj-Napoca , Romania
| | - Simion Bran
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Alexandru Radu Biris
- c National Institute for Research and Development of Isotopic and Molecular Technologies , Cluj-Napoca , Romania
| | - Lucia Hurubeanu
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Mihaela Hedesiu
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Sergiu Vacaras
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | | | - Noemi Dirzu
- e Technical University of Cluj-Napoca , Cluj-Napoca , Romania
| | - Radu Septimiu Campian
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
| | - Grigore Baciut
- a Department of Maxillofacial Surgery and Oral Implantology , "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania
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17
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Saeinasab M, Matin MM, Rassouli FB, Bahrami AR. Blastema cells derived from New Zealand white rabbit's pinna carry stemness properties as shown by differentiation into insulin producing, neural, and osteogenic lineages representing three embryonic germ layers. Cytotechnology 2016; 68:497-507. [PMID: 25371011 PMCID: PMC4846631 DOI: 10.1007/s10616-014-9802-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Accepted: 10/24/2014] [Indexed: 10/24/2022] Open
Abstract
Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capacities. Regeneration is a phenomenon that occurs in a limited number of animals after injury, during which blastema tissue is formed. It has been hypothesized that upon injury, the dedifferentiation of surrounding tissues leads into the appearance of cells with SC characteristics. In present study, stem-like cells (SLCs) were obtained from regenerating tissue of New Zealand white rabbit's pinna and their stemness properties were examined by their capacity to differentiate toward insulin producing cells (IPCs), as well as neural and osteogenic lineages. Differentiation was induced by culture of SLCs in defined medium, and cell fates were monitored by specific staining, RT-PCR and flow cytometry assays. Our results revealed that dithizone positive cells, which represent IPCs, and islet-like structures appeared 1 week after induction of SLCs, and this observation was confirmed by the elevated expression of Ins, Pax6 and Glut4 at mRNA level. Furthermore, SLCs were able to express neural markers as early as 1 week after retinoic acid treatment. Finally, SLCs were able to differentiate into osteogenic lineage, as confirmed by Alizarin Red S staining and RT-PCR studies. In conclusion, SLCs, which could successfully differentiate into cells derived from all three germ layers, can be considered as a valuable model to study developmental biology and regenerative medicine.
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Affiliation(s)
- Morvarid Saeinasab
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
- Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Fatemeh B Rassouli
- Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Ahmad Reza Bahrami
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
- Cell and Molecular Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
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18
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Akadomari K, Tanaka A, Mataga I. Regenerative Capacity of Atrophic Submandibular Gland by Duct Ligation in Mice. J HARD TISSUE BIOL 2016. [DOI: 10.2485/jhtb.25.121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Keita Akadomari
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Niigata, The Nippon Dental University
| | - Akira Tanaka
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Niigata, The Nippon Dental University
| | - Izumi Mataga
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University
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19
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Park JY, Gao G, Jang J, Cho DW. 3D printed structures for delivery of biomolecules and cells: tissue repair and regeneration. J Mater Chem B 2016; 4:7521-7539. [DOI: 10.1039/c6tb01662f] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
This paper reviews the current approaches to using 3D printed structures to deliver bioactive factors (e.g., cells and biomolecules) for tissue repair and regeneration.
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Affiliation(s)
- Ju Young Park
- Division of Integrative Biosciences and Biotechnology
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Republic of Korea
| | - Ge Gao
- Department of Mechanical Engineering
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Republic of Korea
| | - Jinah Jang
- Department of Mechanical Engineering
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Republic of Korea
| | - Dong-Woo Cho
- Department of Mechanical Engineering
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Republic of Korea
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20
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Cancer Stem Cell Plasticity as Tumor Growth Promoter and Catalyst of Population Collapse. Stem Cells Int 2015; 2016:3923527. [PMID: 26858759 PMCID: PMC4686719 DOI: 10.1155/2016/3923527] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 07/22/2015] [Indexed: 12/14/2022] Open
Abstract
It is increasingly argued that cancer stem cells are not a cellular phenotype but rather a transient state that cells can acquire, either through intrinsic signaling cascades or in response to environmental cues. While cancer stem cell plasticity is generally associated with increased aggressiveness and treatment resistance, we set out to thoroughly investigate the impact of different rates of plasticity on early and late tumor growth dynamics and the response to therapy. We develop an agent-based model of cancer stem cell driven tumor growth, in which plasticity is defined as a spontaneous transition between stem and nonstem cancer cell states. Simulations of the model show that plasticity can substantially increase tumor growth rate and invasion. At high rates of plasticity, however, the cells get exhausted and the tumor will undergo spontaneous remission in the long term. In a series of in silico trials, we show that such remission can be facilitated through radiotherapy. The presented study suggests that stem cell plasticity has rather complex, nonintuitive implications on tumor growth and treatment response. Further theoretical, experimental, and integrated studies are needed to fully decipher cancer stem cell plasticity and how it can be harnessed for novel therapeutic approaches.
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21
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Nakano R, Edamura K, Nakayama T, Narita T, Okabayashi K, Sugiya H. Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway. PLoS One 2015; 10:e0141581. [PMID: 26523832 PMCID: PMC4629880 DOI: 10.1371/journal.pone.0141581] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 10/09/2015] [Indexed: 11/26/2022] Open
Abstract
Bone marrow stromal cells (BMSCs) are considered as candidates for regenerative therapy and a useful model for studying neuronal differentiation. The role of basic fibroblast growth factor (bFGF) in neuronal differentiation has been previously studied; however, the signaling pathway involved in this process remains poorly understood. In this study, we investigated the signaling pathway in the bFGF-induced neuronal differentiation of canine BMSCs. bFGF induced the mRNA expression of the neuron marker, microtubule associated protein-2 (MAP2) and the neuron-like morphological change in canine BMSCs. In the presence of inhibitors of fibroblast growth factor receptors (FGFR), phosphatidylinositol 3-kinase (PI3K) and Akt, i.e., SU5402, LY294002, and MK2206, respectively, bFGF failed to induce the MAP2 mRNA expression and the neuron-like morphological change. bFGF induced Akt phosphorylation, but it was attenuated by the FGFR inhibitor SU5402 and the PI3K inhibitor LY294002. In canine BMSCs, expression of FGFR-1 and FGFR-2 was confirmed, but only FGFR-2 activation was detected by cross-linking and immunoprecipitation analysis. Small interfering RNA-mediated knockdown of FGFR-2 in canine BMSCs resulted in the attenuation of bFGF-induced Akt phosphorylation. These results suggest that the FGFR-2/PI3K/Akt signaling pathway is involved in the bFGF-induced neuronal differentiation of canine BMSCs.
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Affiliation(s)
- Rei Nakano
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
- Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
| | - Kazuya Edamura
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
| | - Tomohiro Nakayama
- Laboratory of Veterinary Radiology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
| | - Takanori Narita
- Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
| | - Ken Okabayashi
- Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
| | - Hiroshi Sugiya
- Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino, Fujisawa, Kanagawa, Japan
- * E-mail:
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22
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Comprehensive Review of Adipose Stem Cells and Their Implication in Distraction Osteogenesis and Bone Regeneration. BIOMED RESEARCH INTERNATIONAL 2015; 2015:842975. [PMID: 26448947 PMCID: PMC4584039 DOI: 10.1155/2015/842975] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 08/02/2015] [Indexed: 12/31/2022]
Abstract
Bone is one of the most dynamic tissues in the human body that can heal following injury without leaving a scar. However, in instances of extensive bone loss, this intrinsic capacity of bone to heal may not be sufficient and external intervention becomes necessary. Several techniques are available to address this problem, including autogenous bone grafts and allografts. However, all these techniques have their own limitations. An alternative method is the technique of distraction osteogenesis, where gradual and controlled distraction of two bony segments after osteotomy leads to induction of new bone formation. Although distraction osteogenesis usually gives satisfactory results, its major limitation is the prolonged duration of time required before the external fixator is removed, which may lead to numerous complications. Numerous methods to accelerate bone formation in the context of distraction osteogenesis have been reported. A viable alternative to autogenous bone grafts for a source of osteogenic cells is mesenchymal stem cells from bone marrow. However, there are certain problems with bone marrow aspirate. Hence, scientists have investigated other sources for mesenchymal stem cells, specifically adipose tissue, which has been shown to be an excellent source of mesenchymal stem cells. In this paper, the potential use of adipose stem cells to stimulate bone formation is discussed.
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Wei HJ, Nickoloff JA, Chen WH, Liu HY, Lo WC, Chang YT, Yang PC, Wu CW, Williams DF, Gelovani JG, Deng WP. FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells. Oncotarget 2015; 5:9514-29. [PMID: 25237908 PMCID: PMC4253450 DOI: 10.18632/oncotarget.2413] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Several reports suggest that malignant cells generate phenotypic diversity through fusion with various types of stromal cells within the tumor microenvironment. Mesenchymal stem cell (MSC) is one of the critical components in the tumor microenvironment and a promising fusogenic candidate, but the underlying functions of MSC fusion with malignant cell have not been fully examined. Here, we demonstrate that MSCs fuse spontaneously with lung cancer cells, and the latter is reprogrammed to slow growth and stem-like state. Transcriptome profiles reveal that lung cancer cells are reprogrammed to a more benign state upon MSC fusion. We further identified FOXF1 as a reprogramming mediator that contributes not only to the reprogramming toward stemness but also to the p21-regulated growth suppression in fusion progeny. Collectively, MSC fusion does not enhance the intrinsic malignancy of lung cancer cells. The anti-malignant effects of MSC fusion-induced reprogramming on lung cancer cells were accomplished by complementation of tumorigenic defects, including restoration of p21 function and normal terminal differentiation pathways as well as up-regulation of FOXF1, a putative tumor suppressor. Such fusion process raises the therapeutic potential that MSC fusion can be utilized to reverse cellular phenotypes in cancer.
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Affiliation(s)
- Hong-Jian Wei
- Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan
| | - Jac A Nickoloff
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Wei-Hong Chen
- Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan
| | - Hen-Yu Liu
- Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan
| | - Wen-Cheng Lo
- Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan. School of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Ya-Ting Chang
- Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Pan-Chyr Yang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Cheng-Wen Wu
- Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 112, Taiwan
| | - David F Williams
- Wake Forest Institute of Regenerative Medicine, Winston-Salem, NC 27157, USA
| | - Juri G Gelovani
- Department of Biomedical Engineering, College of Engineering and School of Medicine, Wayne State University, Detroit, MI 48201, USA Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA
| | - Win-Ping Deng
- Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan
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24
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Is reduction of tumor burden sufficient for the 21st century? Cancer Lett 2015; 356:149-55. [PMID: 24632530 DOI: 10.1016/j.canlet.2014.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Revised: 02/11/2014] [Accepted: 03/04/2014] [Indexed: 12/21/2022]
Abstract
Currently, animal models are used to test the efficacy of tumor treatment. A significant reduction of tumor mass is lauded as great improvement. As we begin the 21st century, one wonders if this is sufficient and acceptable for cancer treatment. Although the presence of cancer stem cell (CSCs) is not a new phenomenon, their role in the initiation of the tumor for clinical resurgence is mostly ignored when testing drugs. The current treatment then poses a major limitation to aggressively target the cells most responsible for tumor initiation and resurgence. The review does not trivialize the problem since it is acknowledged that the tumors and cells within the tissue microenvironment would interact through complex mechanisms. It is quite possible that the interaction by CSCs and the microenvironment will vary, depending on the tissue, e.g., bone marrow versus brain. Research studies are needed to investigate if CSCs from the same organ differ after migrating to other tissues. If so, this will pose an economic dilemma for targeted drug development. It will not be feasible to develop drugs for each organ. Besides, the cost, there could be problems to effectively deliver the drugs to all organs, problems to assess drug distribution to particular tissues and toxicity for specific drugs. If multiple drugs are required to eradicate CSCs in different tissues, there is a problem of possible untoward effect for the simultaneous delivery of multiple drugs to a single cancer patient. As new drugs are developed, the investigators will need to pay attention for dedifferentiation of non-CSCs to CSCs. The metabolic pathways will have to be given equal attention as the stem cells genes since their pathways might show major differences rather than the stem cells genes, which are shared by the normal stem cells.
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25
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Abstract
This review discusses quantitative modeling studies of stem and non-stem cancer cell interactions and the fraction of cancer stem cells.
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Affiliation(s)
- Heiko Enderling
- Department of Integrated Mathematical Oncology
- H. Lee Moffitt Cancer Center & Research Institute
- Tampa
- USA
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26
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Hodgetts SI, Stagg K, Sturm M, Edel M, Blancafort P. Long live the stem cell: the use of stem cells isolated from post mortem tissues for translational strategies. Int J Biochem Cell Biol 2014; 56:74-81. [PMID: 25300917 DOI: 10.1016/j.biocel.2014.09.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 09/26/2014] [Accepted: 09/30/2014] [Indexed: 01/18/2023]
Abstract
The "stem cell" has become arguably one of the most important biological tools in the arsenal of translational research directed at regeneration and repair. It remains to be seen whether every tissue has its own stem cell niche, although relatively recently a large amount of research has focused on isolating and characterizing tissue-specific stem cell populations, as well as those that are able to be directed to transdifferentiate into a variety of different lineages. Traditionally, stem cells are isolated from the viable tissue of embryonic, fetal, or adult living hosts; from "fresh" donated tissues that have been surgically or otherwise removed (biopsies), or obtained directly from tissues within minutes to several hours post mortem (PM). These human progenitor/stem cell sources remain potentially highly controversial, since they are accompanied by various still-unresolved ethical, social, moral and legal challenges. Due to the limited number of "live" donors, the small amount of material obtained from biopsies and difficulties during purification processes, harvesting from cadaveric material presents itself as an alternative strategy that could provide a hitherto untapped source of stem cells. However, PM stem cells are not without their own unique set of limitations including difficulty of obtaining samples, limited supply of material, variations in delay between death and sample collection, possible lack of medication history and suboptimal retrospective assignment of diagnostic and demographic data. This article is part of a Directed Issue entitled: Regenerative Medicine: The challenge of translation.
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Affiliation(s)
- Stuart I Hodgetts
- School of Anatomy Physiology & Human Biology, The University of Western Australia, Crawley, Western Australia, Australia.
| | - Kelda Stagg
- School of Anatomy Physiology & Human Biology, The University of Western Australia, Crawley, Western Australia, Australia
| | - Marian Sturm
- Cell and Tissue Therapies WA, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Michael Edel
- Control of Pluripotency Laboratory, Department of Physiological Sciences I, Faculty of Medicine, University of Barcelona, Hospital Clinic, Casanova 143, 08036 Barcelona, Spain; University of Sydney Medical School, Faculty of Medicine, Westmead Children's Hospital, Division of Pediatrics and Child Health, Sydney, Australia
| | - Pilar Blancafort
- School of Anatomy Physiology & Human Biology, The University of Western Australia, Crawley, Western Australia, Australia; Cancer Epigenetics Group, The Harry Perkins Institute for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia
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27
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Nakano R, Edamura K, Nakayama T, Teshima K, Asano K, Narita T, Okabayashi K, Sugiya H. Differentiation of canine bone marrow stromal cells into voltage- and glutamate-responsive neuron-like cells by basic fibroblast growth factor. J Vet Med Sci 2014; 77:27-35. [PMID: 25284120 PMCID: PMC4349535 DOI: 10.1292/jvms.14-0284] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
We investigated the in vitro differentiation of canine bone marrow stromal cells (BMSCs) into voltage- and glutamate-responsive neuron-like cells. BMSCs were obtained from the bone marrow of healthy beagle dogs. Canine BMSCs were incubated with the basal medium for neurons containing recombinant human basic fibroblast growth factor (bFGF; 100 ng/ml). The viability of the bFGF-treated cells was assessed by a trypan blue exclusion assay, and the morphology was monitored. Real-time RT-PCR was performed to evaluate mRNA expression of neuronal, neural stem cell and glial markers. Western blotting and immunocytochemical analysis for the neuronal markers were performed to evaluate the protein expression and localization. The Ca(2+) mobilization of the cells was evaluated using the Ca(2+) indicator Fluo3 to monitor Ca(2+) influx. To investigate the mechanism of bFGF-induced neuronal differentiation, the fibroblast growth factor receptor inhibitor, the phosphoinositide 3-kinase inhibitor or the Akt inhibitor was tested. The bFGF treatment resulted in the maintenance of the viability of canine BMSCs for 10 days, in the expression of neuronal marker mRNAs and proteins and in the manifestation of neuron-like morphology. Furthermore, in the bFGF-treated BMSCs, a high concentration of KCl and L-glutamate induced an increase in intracellular Ca(2+) levels. Each inhibitor significantly attenuated the bFGF-induced increase in neuronal marker mRNA expression. These results suggest that bFGF contributes to the differentiation of canine BMSCs into voltage- and glutamate-responsive neuron-like cells and may lead to the development of new cell-based treatments for neuronal diseases.
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Affiliation(s)
- Rei Nakano
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan
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28
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Sciancalepore AG, Sallustio F, Girardo S, Gioia Passione L, Camposeo A, Mele E, Di Lorenzo M, Costantino V, Schena FP, Pisignano D. A bioartificial renal tubule device embedding human renal stem/progenitor cells. PLoS One 2014; 9:e87496. [PMID: 24498117 PMCID: PMC3907467 DOI: 10.1371/journal.pone.0087496] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 12/24/2013] [Indexed: 12/20/2022] Open
Abstract
We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs) was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na+K+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5)% and (13±5)%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative “lab-on-a-chip” platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.
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Affiliation(s)
- Anna Giovanna Sciancalepore
- Center for Biomolecular Nanotechnologies, Istituto Italiano di Tecnologia, Arnesano, Italy
- * E-mail: (AGS); (DP)
| | - Fabio Sallustio
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Centro Addestramento Ricerca Scientifica in Oncologia (C.A.R.S.O.) Consortium, Valenzano, Italy
- Department of Science, Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy
| | - Salvatore Girardo
- National Nanotechnology Laboratory of Istituto Nanoscienze-CNR, Lecce, Italy
| | - Laura Gioia Passione
- Center for Biomolecular Nanotechnologies, Istituto Italiano di Tecnologia, Arnesano, Italy
- National Nanotechnology Laboratory of Istituto Nanoscienze-CNR, Lecce, Italy
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Universitá del Salento, Lecce, Italy
| | - Andrea Camposeo
- Center for Biomolecular Nanotechnologies, Istituto Italiano di Tecnologia, Arnesano, Italy
- National Nanotechnology Laboratory of Istituto Nanoscienze-CNR, Lecce, Italy
| | - Elisa Mele
- Center for Biomolecular Nanotechnologies, Istituto Italiano di Tecnologia, Arnesano, Italy
| | - Mirella Di Lorenzo
- National Nanotechnology Laboratory of Istituto Nanoscienze-CNR, Lecce, Italy
| | - Vincenzo Costantino
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Francesco Paolo Schena
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Centro Addestramento Ricerca Scientifica in Oncologia (C.A.R.S.O.) Consortium, Valenzano, Italy
| | - Dario Pisignano
- Center for Biomolecular Nanotechnologies, Istituto Italiano di Tecnologia, Arnesano, Italy
- National Nanotechnology Laboratory of Istituto Nanoscienze-CNR, Lecce, Italy
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Universitá del Salento, Lecce, Italy
- * E-mail: (AGS); (DP)
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29
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Zhao X, Liu L, Wang J, Xu Y, Zhang W, Khang G, Wang X. In vitro vascularization of a combined system based on a 3D printing technique. J Tissue Eng Regen Med 2014; 10:833-842. [PMID: 24399638 DOI: 10.1002/term.1863] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Revised: 11/23/2013] [Accepted: 11/25/2013] [Indexed: 11/07/2022]
Abstract
A vital challenge in complex organ manufacturing is to vascularize large combined tissues. The aim of this study is to vascularize in vitro an adipose-derived stem cell (ADSC)/fibrin/collagen incorporated three-dimensional (3D) poly(d,l-lactic-co-glycolic acid) (PLGA) scaffold (10 × 10 × 10 mm3 ) with interconnected channels. A low-temperature 3D printing technique was employed to build the PLGA scaffold. A step-by-step cocktail procedure was designed to engage or steer the ADSCs in the PLGA channels towards both endothelial and smooth muscle cell lineages. The combined system had sufficient mechanical properties to support the cell/fibrin/collagen hydrogel inside the predefined PLGA channels. The ADSCs encapsulated in the fibrin/collagen hydrogel differentiated to endothelial and smooth muscle cell lineage, respectively, corresponding to their respective locations in the construct and formed vascular-like structures. This technique allows in vitro vascularization of the predefined PLGA channels and provides a choice for complex organ manufacture. Copyright © 2014 John Wiley & Sons, Ltd.
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Affiliation(s)
- Xinru Zhao
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Libiao Liu
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Jiayin Wang
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Yufan Xu
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Weiming Zhang
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Gilson Khang
- Department of BIN Fusion Technology and Department of Polymer Nano Science Technology, Chonbuk National University, Jeonju, Korea
| | - Xiaohong Wang
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing, China. .,State Key Laboratory of Materials Processing and Die and Mould Technology, Huazhong University of Science and Technology, Wuhan, China.
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30
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Verine J, Varna M, Ratajczak P, El-Bouchtaoui M, Leboeuf C, Plassa LF, Soliman H, Sandid W, Abboud I, Bousquet G, Verneuil L, Peraldi MN, Mongiat-Artus P, Janin A. Human de novo papillary renal-cell carcinomas in a kidney graft: evidence of recipient origin with adenoma-carcinoma sequence. Am J Transplant 2013; 13:984-992. [PMID: 23425311 DOI: 10.1111/ajt.12163] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2012] [Revised: 12/17/2012] [Accepted: 12/26/2012] [Indexed: 01/25/2023]
Abstract
Papillary renal-cell carcinoma (pRCC) is unusual for its occurrence in kidneys with chronic dysfunction, for its frequent multifocality and for its common association with papillary adenoma, a benign renal lesion morphologically indistinguishable from pRCC. Concomitant development of papillary adenoma and pRCC in five transplanted kidneys, where donor and recipient characteristics are well established, provided a unique opportunity for molecular studies of de novo pRCC carcinogenesis. We aimed to study this tumor type to determine whether or not the different papillary tumors have the same origin, and whether or not papillary adenomas are precursor lesions of pRCC. We performed XY-FISH in sex-mismatched kidney transplants, and polymorphic microsatellite DNA and high-resolution melting of mitochondrial DNA analyzes in all five patients on laser-microdissected tumor cells, then compared these molecular profiles to donor and recipient profiles. This study (i) identified the recipient origin of de novo papillary adenomas and pRCCs in a kidney transplant, (ii) demonstrated an identical origin for precursor cells of papillary adenomas and pRCCs and (iii) showed additional genetic alterations in pRCCs compared to papillary adenomas. This molecular approach of papillary tumors developed in transplanted kidney identified successive steps in carcinogenesis of human de novo papillary renal-cell carcinoma.
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Affiliation(s)
- J Verine
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France.,AP-HP, Hôpital Saint-Louis, Department of Pathology, Paris, F-75010, France
| | - M Varna
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France
| | - P Ratajczak
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France
| | - M El-Bouchtaoui
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France
| | - C Leboeuf
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France
| | - L-F Plassa
- AP-HP, Hôpital Saint-Louis, Department of Biochemistry, Paris, F-75010, France
| | - H Soliman
- AP-HP, Hôpital Saint-Louis, Department of Biochemistry, Paris, F-75010, France
| | - W Sandid
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France.,AP-HP, Hôpital Saint-Louis, Department of Pathology, Paris, F-75010, France
| | - I Abboud
- AP-HP, Hôpital Saint-Louis, Department of Nephrology and Renal Transplantation, Paris, F-75010, France
| | | | | | - M-N Peraldi
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France.,AP-HP, Hôpital Saint-Louis, Department of Nephrology and Renal Transplantation, Paris, F-75010, France
| | - P Mongiat-Artus
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France.,AP-HP, Hôpital Saint-Louis, Department of Urology, Paris, F-75010, France
| | - A Janin
- Inserm, U 728, Paris, F-75010, France.,Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 728, F-75010, Paris, France.,AP-HP, Hôpital Saint-Louis, Department of Pathology, Paris, F-75010, France
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31
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Scarlett CJ. Contribution of bone marrow derived cells to the pancreatic tumor microenvironment. Front Physiol 2013; 4:56. [PMID: 23531764 PMCID: PMC3607802 DOI: 10.3389/fphys.2013.00056] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 03/08/2013] [Indexed: 12/18/2022] Open
Abstract
Pancreatic cancer is a complex, aggressive, and heterogeneous malignancy driven by the multifaceted interactions within the tumor microenvironment. While it is known that the tumor microenvironment accommodates many cell types, each playing a key role in tumorigenesis, the major source of these stromal cells is not well-understood. This review examines the contribution of bone marrow-derived cells (BMDC) to pancreatic carcinogenesis, with respect to their role in constituting the tumor microenvironment. In particular, their role in supporting fibrosis, immunosuppression, and neovascularization will be discussed.
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Affiliation(s)
- Christopher J Scarlett
- Food Bioactives and Pancreatic Cancer Biology Group, School of Environmental and Life Sciences, University of Newcastle Ourimbah, NSW, Australia ; Cancer Research Program, Garvan Institute of Medical Research Darlinghurst, Sydney, NSW, Australia
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32
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Yokoo T, Fukui A, Kobayashi E. Application of regenerative medicine for kidney diseases. Organogenesis 2012; 3:34-43. [PMID: 19279698 DOI: 10.4161/org.3.1.3961] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application.
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Affiliation(s)
- Takashi Yokoo
- Division of Nephrology and Hypertension; Department of Internal Medicine; The Jikei University School of Medicine; Tokyo, Japan
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33
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Nery AA, Nascimento IC, Glaser T, Bassaneze V, Krieger JE, Ulrich H. Human mesenchymal stem cells: from immunophenotyping by flow cytometry to clinical applications. Cytometry A 2012; 83:48-61. [PMID: 23027703 DOI: 10.1002/cyto.a.22205] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Revised: 08/15/2012] [Accepted: 08/22/2012] [Indexed: 12/25/2022]
Abstract
Modern medicine will unequivocally include regenerative medicine as a major breakthrough in the re-establishment of damaged or lost tissues due to degenerative diseases or injury. In this scenario, millions of patients worldwide can have their quality of life improved by stem cell implantation coupled with endogenous secretion or administration of survival and differentiation promoting factors. Large efforts, relying mostly on flow cytometry and imaging techniques, have been put into cell isolation, immunophenotyping, and studies of differentiation properties of stem cells of diverse origins. Mesenchymal stem cells (MSCs) are particularly relevant for therapy due to their simplicity of isolation. A minimal phenotypic pattern for the identification of MSCs cells requires them to be immunopositive for CD73, CD90, and CD105 expression, while being negative for CD34, CD45, and HLA-DR and other surface markers. MSCs identified by their cell surface marker expression pattern can be readily purified from patient's bone marrow and adipose tissues. Following expansion and/or predifferentiation into a desired tissue type, stem cells can be reimplanted for tissue repair in the same patient, virtually eliminating rejection problems. Transplantation of MSCs is subject of almost 200 clinical trials to cure and treat a very broad range of conditions, including bone, heart, and neurodegenerative diseases. Immediate or medium term improvements of clinical symptoms have been reported as results of many clinical studies.
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Affiliation(s)
- Arthur A Nery
- Departamento de Bioquímica, Universidade de São Paulo, São Paulo, Brazil
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34
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Nucera E, Nicoletti C, Chiapparino C, Pacello ML, D'Alessio V, Musarò A, De Santis R. AvidinOX™ for tissue targeted delivery of biotinylated cells. Int J Immunopathol Pharmacol 2012; 25:239-46. [PMID: 22507336 DOI: 10.1177/039463201202500126] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
AvidinOX™, a product containing aldehyde groups, generated by ligand-assisted sugar oxidation of avidin by sodium periodate, maintains the capacity to bind biotin with very high affinity and exhibits the property to chemically link cellular and tissue proteins through Schiff's base formation thus residing in tissues for weeks. In recent studies, we have shown that AvidinOX exhibits much higher persistency in the skeletal muscle than native avidin. The aim of the present study is to evaluate whether AvidinOX-biotin interaction might be exploited to target biotinylated cells to an AvidinOX pre-treated muscle. To accomplish this we performed the following experiments: 1) The proliferation and differentiation properties of biotinylated C2C12 myoblasts were tested in vitro upon linkage to AvidinOX; 2) Bone marrow-derived cells (BMDC) were isolated from GFP positive transgenic mice [strain C57 BL/6-tg (UBC-GFP)] and after biotinylation (bBMDC) were intravenously administered to naive and MAVA+ (Mouse anti Avidin Antibody) C57/B6 mice previously injected with AvidinOX in a tibial muscle (TM). Localization efficiency of GFP+ bBMDC was evaluated on serial sections of the AvidinOX- and vehicle-treated (contra lateral limb) TM, 5 days after transplantation. Results show that biotinylated C2C12 cells, once linked to AvidinOX, maintain their proliferation and differentiation capacity, in vitro. Intravenous injection of biotinylated GFP+ bone marrow-derived cells leads to their specific and efficient localization in the AvidinOX-pre-treated, but not contra lateral muscle of both naive and MAVA+ mice. The present data suggest a potential use of AvidinOX to improve tissue targeted delivery of biotinylated cells.
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Affiliation(s)
- E Nucera
- Department of Biotechnology, R&D Sigma-tau Industrie Farmaceutiche Riunite S.p.A. Pomezia, Italy
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35
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Branco É, Cabral R, Gomes BD, Kfoury JR, Miglino MA. Bone marrow cells of swine: Collection and separation. Microsc Res Tech 2012; 75:917-20. [DOI: 10.1002/jemt.22013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Accepted: 12/22/2011] [Indexed: 11/10/2022]
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36
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Jeon BG, Kwack DO, Rho GJ. Variation of telomerase activity and morphology in porcine mesenchymal stem cells and fibroblasts during prolonged in vitro culture. Anim Biotechnol 2012; 22:197-210. [PMID: 22132813 DOI: 10.1080/10495398.2011.624651] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The purpose of this study was to examine the telomerase activity, population doubling time (PDT), morphological alterations, and the cell cycle status with activity of senescence-associated-ß-galactosidase in porcine mesenchymal stem cells (MSCs) and fibroblasts during an extended in vitro culture. MSCs and fibroblasts were isolated from bone marrow and ear skin of a miniature pig, respectively, and cultured up to 20 passages. The analysis was carried out in MSCs and fibroblasts at 1, 5, 10, 15, and 20 passages. Relative telomerase activity (RTA) levels were significantly (P < 0.05) higher in MSCs than in fibroblasts at all the passages. The PDT and cellular size slightly increased in MSCs at later passages. In contrast, fibroblasts had significantly (P < 0.05) increased PDT and cellular size, and the morphology revealed senescent-like abnormal type after passage 10. Further, the high incidence of ß-galactosidase stained cells was observed in fibroblasts compared to that of MSCs at passage 15, and cell cycle stage at G0 / G1 phase was significantly (P < 0.05) increased in the fibroblasts at 15 and 20 passages compared to that of MSCs. Based on these observations, we concluded that porcine MSCs possessed more tolerance against senescence and aging compared to fibroblasts following prolonged in vitro culture.
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Affiliation(s)
- Byeong-Gyun Jeon
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea
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37
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Diaz-Cano SJ. Tumor heterogeneity: mechanisms and bases for a reliable application of molecular marker design. Int J Mol Sci 2012; 13:1951-2011. [PMID: 22408433 PMCID: PMC3292002 DOI: 10.3390/ijms13021951] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 01/23/2012] [Accepted: 02/01/2012] [Indexed: 12/22/2022] Open
Abstract
Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.
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Affiliation(s)
- Salvador J. Diaz-Cano
- Department Histopathology, King’s College Hospital and King’s Health Partners, Denmark Hill, London SE5 9RS, UK; E-Mail: ; Tel.: +44-20-3299-3041; Fax: +44-20-3299-3670
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38
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You S, Tariq A, Kublin CL, Zoukhri D. Detection of BrdU-label retaining cells in the lacrimal gland: implications for tissue repair. Cell Tissue Res 2011; 346:317-26. [PMID: 22101331 DOI: 10.1007/s00441-011-1271-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2011] [Accepted: 10/24/2011] [Indexed: 10/15/2022]
Abstract
The purpose of the present study was to determine if the lacrimal gland contains 5-bromo-2'-deoxyuridine (BrdU)-label retaining cells and if they are involved in tissue repair. Animals were pulsed daily with BrdU injections for 7 consecutive days. After a chase period of 2, 4, or 12 weeks, the animals were sacrificed and the lacrimal glands were removed and processed for BrdU immunostaining. In another series of experiments, the lacrimal glands of 12-week chased animals were either left untreated or were injected with interleukin 1 (IL-1) to induce injury. Two and half days post-injection, the lacrimal glands were removed and processed for BrdU immunostaining. After 2 and 4 weeks of chase period, a substantial number of lacrimal gland cells were BrdU(+) (11.98 ± 1.84 and 7.95 ± 1.83 BrdU(+) cells/mm(2), respectively). After 12 weeks of chase, there was a 97% decline in the number of BrdU(+) cells (0.38 ± 0.06 BrdU(+) cells/mm(2)), suggesting that these BrdU-label retaining cells may represent slow-cycling adult stem/progenitor cells. In support of this hypothesis, the number of BrdU labeled cells increased over 7-fold during repair of the lacrimal gland (control: 0.41 ± 0.09 BrdU(+) cells/mm(2); injured: 2.91 ± 0.62 BrdU(+) cells/mm(2)). Furthermore, during repair, among BrdU(+) cells 58.2 ± 3.6 % were acinar cells, 26.4 ± 4.1% were myoepithelial cells, 0.4 ± 0.4% were ductal cells and 15.0 ± 3.0% were stromal cells. We conclude that the murine lacrimal gland contains BrdU-label retaining cells that are mobilized following injury to generate acinar, myoepithelial and ductal cells.
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Affiliation(s)
- Samantha You
- Department of General Dentistry, Tufts University School of Dental Medicine, Boston, MA 0211, USA
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Scarlett CJ, Colvin EK, Pinese M, Chang DK, Morey AL, Musgrove EA, Pajic M, Apte M, Henshall SM, Sutherland RL, Kench JG, Biankin AV. Recruitment and activation of pancreatic stellate cells from the bone marrow in pancreatic cancer: a model of tumor-host interaction. PLoS One 2011; 6:e26088. [PMID: 22022519 PMCID: PMC3193536 DOI: 10.1371/journal.pone.0026088] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Accepted: 09/19/2011] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND AND AIMS Chronic pancreatitis and pancreatic cancer are characterised by extensive stellate cell mediated fibrosis, and current therapeutic development includes targeting pancreatic cancer stroma and tumor-host interactions. Recent evidence has suggested that circulating bone marrow derived stem cells (BMDC) contribute to solid organs. We aimed to define the role of circulating haematopoietic cells in the normal and diseased pancreas. METHODS Whole bone marrow was harvested from male β-actin-EGFP donor mice and transplanted into irradiated female recipient C57/BL6 mice. Chronic pancreatitis was induced with repeat injections of caerulein, while carcinogenesis was induced with an intrapancreatic injection of dimethylbenzanthracene (DMBA). Phenotype of engrafted donor-derived cells within the pancreas was assessed by immunohistochemistry, immunofluorescence and in situ hybridisation. RESULTS GFP positive cells were visible in the exocrine pancreatic epithelia from 3 months post transplantation. These exhibited acinar morphology and were positive for amylase and peanut agglutinin. Mice administered caerulein developed chronic pancreatitis while DMBA mice exhibited precursor lesions and pancreatic cancer. No acinar cells were identified to be donor-derived upon cessation of cerulein treatment, however rare occurrences of bone marrow-derived acinar cells were observed during pancreatic regeneration. Increased recruitment of BMDC was observed within the desmoplastic stroma, contributing to the activated pancreatic stellate cell (PaSC) population in both diseases. Expression of stellate cell markers CELSR3, PBX1 and GFAP was observed in BMD cancer-associated PaSCs, however cancer-associated, but not pancreatitis-associated BMD PaSCs, expressed the cancer PaSC specific marker CELSR3. CONCLUSIONS This study demonstrates that BMDC can incorporate into the pancreas and adopt the differentiated state of the exocrine compartment. BMDC that contribute to the activated PaSC population in chronic pancreatitis and pancreatic cancer have different phenotypes, and may play important roles in these diseases. Further, bone marrow transplantation may provide a useful model for the study of tumor-host interactions in cancer and pancreatitis.
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Affiliation(s)
- Christopher J. Scarlett
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - Emily K. Colvin
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - Mark Pinese
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - David K. Chang
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
- Division of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, Australia
| | - Adrienne L. Morey
- Department of Anatomical Pathology, St Vincent's Hospital, Darlinghurst, Australia
| | - Elizabeth A. Musgrove
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - Marina Pajic
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - Minoti Apte
- South Western Sydney Clinical School, The University of New South Wales, Sydney, Australia
| | - Susan M. Henshall
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - Robert L. Sutherland
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
| | - James G. Kench
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
- Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia
| | - Andrew V. Biankin
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
- Division of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, Australia
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Nadig RR. Stem cell therapy - Hype or hope? A review. J Conserv Dent 2011; 12:131-8. [PMID: 20543921 PMCID: PMC2879724 DOI: 10.4103/0972-0707.58329] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2009] [Revised: 10/10/2009] [Accepted: 10/15/2009] [Indexed: 12/18/2022] Open
Abstract
While the regeneration of a lost tissue is known to mankind for several years, it is only in the recent past that research on regenerative medicine/dentistry has gained momentum and eluded the dramatic yet scientific advancements in the field of molecular biology. The growing understanding of biological concepts in the regeneration of oral/dental tissues coupled with experiments on stem cells is likely to result in a paradigm shift in the therapeutic armamentarium of dental and oral diseases culminating in an intense search for “biological solutions to biological problems.” Stem cells have been successfully isolated from variety of human tissues including orofacial tissues. Initial evidence from pioneering studies has documented the likely breakthrough that stem cells offer for various life-threatening diseases that have so far defeated modern medical care. The evidence gathered so far has propelled many elegant studies exploring the role of stem cells and their manifold dental applications. This review takes you on a sojourn of the origin of stem cells, their properties, characteristics, current research, and their potential applications. It also focuses on the various challenges and barriers that we have to surmount before translating laboratory results to successful clinical applications heralding the dawn of regenerative dentistry.
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Affiliation(s)
- Roopa R Nadig
- Department of Conservative Dentistry and Endodontics, Dayananda Sagar College of Dental Sciences, Bangalore, Karnataka, India
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Yu T, Lan SY, Wu B, Pan QH, Shi L, Huang KH, Lin Y, Chen QK. Musashi1 and hairy and enhancer of split 1 high expression cells derived from embryonic stem cells enhance the repair of small-intestinal injury in the mouse. Dig Dis Sci 2011; 56:1354-1368. [PMID: 21221806 DOI: 10.1007/s10620-010-1441-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2010] [Accepted: 09/19/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND Embryonic stem cells have great plasticity. In this study, we repaired impaired small intestine by transplanting putative intestinal epithelial stem cells (Musashi1 and hairy and enhancer of split 1 high expression cells) derived from embryonic stem cells. METHODS The differentiation of definitive endoderm in embryoid bodies, derived from male ES-E14TG2a cells by the hanging-drop method, was monitored to define a time point for maximal induction of putative intestinal epithelial stem cells by epidermal growth factor. Furthermore, to evaluate the regenerative potential of intestinal epithelium, these putative stem cells were engrafted into NOD/SCID mice and female mice with enteritis. Donor cells were located by SRY DNA in situ hybridization. RESULTS The results revealed that definitive endodermal markers were highly expressed in 5-day embryoid bodies. These embryoid body cells were induced into putative intestinal epithelial stem cells on the 5th day of epidermal growth factor administration. Grafts from these cells consisted of adenoid structures and nonspecific structural cells with strong expression of small-intestinal epithelial cell markers. In situ hybridization revealed that the donor cells could specifically locate in damaged intestinal epithelium, contribute to epithelial structures, and enhance regeneration. CONCLUSIONS In conclusion, the Musashi1 and hairy and enhancer of split 1 high expression cells, derived from mouse embryonic stem cells, locate predominantly in impaired small-intestinal epithelium after transplantation and contribute to epithelial regeneration.
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Affiliation(s)
- Tao Yu
- Department of Gastroenterology, The Second Affiliated Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, 510120, Guangzhou, Guangdong, People's Republic of China
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Gordon D, Pavlovska G, Uney JB, Wraith DC, Scolding NJ. Human mesenchymal stem cells infiltrate the spinal cord, reduce demyelination, and localize to white matter lesions in experimental autoimmune encephalomyelitis. J Neuropathol Exp Neurol 2010; 69:1087-95. [PMID: 20940628 DOI: 10.1097/nen.0b013e3181f97392] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Mesenchymal stem cells (MSCs) can abrogate the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), but whether this therapeutic effect occurs entirely through systemic immune modulation and whether CNS infiltration occurs after peripheral delivery are uncertain. We studied the clinical and neuropathologic effects of intravenously administered human MSCs (hMSCs) in C57BL/6 mice with EAE. Human MSCs significantly reduced the clinical disease severity, particularly in later disease. Large numbers of hMSCs migrated into gray and white matter at all levels of the spinal cord in both naive mice and mice with EAE. In the latter, hMSCs accumulated over time in demyelinated areas. There were 2 distinct morphological appearances of the hMSCs in the tissue, that is, rounded and less numerous process-bearing forms; very few expressed neural markers. The number of spinal cord white matter lesions and areas of white matter demyelination were reduced after hMSC treatment compared with control treatment. These findings show that central nervous system infiltration occurs after peripheral delivery of hMSCs, that they accumulate where there is myelin damage, and that they are associated with a reduced extent of demyelination. These data support a potential role for hMSCs in autologous cell therapy in multiple sclerosis.
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MESH Headings
- Animals
- Demyelinating Diseases/etiology
- Demyelinating Diseases/pathology
- Demyelinating Diseases/surgery
- Disease Models, Animal
- Encephalomyelitis, Autoimmune, Experimental/complications
- Encephalomyelitis, Autoimmune, Experimental/pathology
- Encephalomyelitis, Autoimmune, Experimental/surgery
- Green Fluorescent Proteins/genetics
- Humans
- Mesenchymal Stem Cell Transplantation/methods
- Mesenchymal Stem Cells/physiology
- Mice
- Mice, Inbred C57BL
- Myelin Sheath/metabolism
- Myelin Sheath/pathology
- Nerve Fibers, Myelinated/pathology
- Nerve Tissue Proteins/metabolism
- Neurologic Examination/methods
- Neutrophil Infiltration
- Spinal Cord/pathology
- Transduction, Genetic
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Affiliation(s)
- David Gordon
- MS Labs, Burden Centre, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, United Kingdom
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Kresnowati MTAP, Forde GM, Chen XD. Model-based analysis and optimization of bioreactor for hematopoietic stem cell cultivation. Bioprocess Biosyst Eng 2010; 34:81-93. [PMID: 20652600 DOI: 10.1007/s00449-010-0449-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2010] [Accepted: 06/24/2010] [Indexed: 10/19/2022]
Abstract
One of the problems to be solved in attaining the full potentials of hematopoietic stem cell (HSC) applications is the limited availability of the cells. Growing HSCs in a bioreactor offers an alternative solution to this problem. Besides, it also offers the advantages of eliminating labour intensive process as well as the possible contamination involved in the periodic nutrient replenishments in the traditional T-flask stem cell cultivation. In spite of this, the optimization of HSC cultivation in a bioreactor has been barely explored. This manuscript discusses the development of a mathematical model to describe the dynamics in nutrient distribution and cell concentration of an ex vivo HSC cultivation in a microchannel perfusion bioreactor. The model was further used to optimize the cultivation by proposing three alternative feeding strategies in order to prevent the occurrence of nutrient limitation in the bioreactor. The evaluation of these strategies, the periodic step change increase in the inlet oxygen concentration, the periodic step change increase in the media inflow, and the feedback control of media inflow, shows that these strategies can successfully improve the cell yield of the bioreactor. In general, the developed model is useful for the design and optimization of bioreactor operation.
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Affiliation(s)
- M T A P Kresnowati
- Bioprocess and Microbiology Laboratory, Department of Chemical Engineering, Faculty of Industrial Technology, Bandung Institute of Technology, Ganesha 10, Bandung 40132, Indonesia.
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Borena BM, Pawde AM, Amarpal, Aithal HP, Kinjavdekar P, Singh R, Kumar D. Evaluation of autologous bone marrow-derived nucleated cells for healing of full-thickness skin wounds in rabbits. Int Wound J 2010; 7:249-60. [PMID: 20492002 DOI: 10.1111/j.1742-481x.2010.00683.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The aim of the study was to evaluate the potential of autologous bone marrow-derived nucleated cells to enhance the rate of healing of full-thickness excisional skin wounds in rabbits. The study was conducted on 20 New Zealand white rabbits of either sex. Two, 2 x 2 cm full-thickness skin (thoracolumabar region) excisional wounds were created; one on each side of the dorsal midline in each animal. The wounds were randomly assigned to either injection of autologous bone marrow-derived nucleated cells into the wound margins (BI), or topical application of sterile saline solution (normal saline, NS), which served as control. The wound healing was assessed by evaluation of granulation tissue formation, wound contraction, epithelisation and histopathological and histochemical changes up to 28 days after creation of the wound. Granulation tissue appeared significantly faster in BI-treated wounds (3.22 +/- 0.22 days) than in NS-treated wounds (4.56 +/- 0.47 days). Better epithelisation was seen histologically in BI wounds than in NS-treated wounds. Wound contraction was significantly more in BI wounds when compared with NS wounds on 21 post-surgery. Histopathological examination of the healing tissue showed early disappearance of inflammatory reaction, significantly more neovascularisation, and more fibroplasias and early lay down and histological maturation of collagen in BI wounds than in control wounds. It was concluded that injection of autologous bone marrow-derived nucleated cells in the wound margins induced faster and better quality healing of excisional skin wounds in rabbits when compared with normal saline. The injection of autologous bone marrow-derived nucleated cells can be used to promote healing of large full-thickness skin wounds in rabbits.
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Affiliation(s)
- B M Borena
- Division of Surgery, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
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Borena BM, Pawde AM, Amarpal, Aithal HP, Kinjavdekar P, Singh R, Kumar D. Autologous bone marrow-derived cells for healing excisional dermal wounds of rabbits. Vet Rec 2010; 165:563-8. [PMID: 19897871 DOI: 10.1136/vr.165.19.563] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
The wound-healing potential of autologous bone marrow-derived nucleated cells was evaluated in full-thickness skin wounds in the thoracolumbar region of 20 clinically healthy rabbits. Three wounds of 2 x 2 cm, one on the left side and two right of the midline, were created on the dorsal lumbar region of each rabbit under xylazine-ketamine anaesthesia. The wounds of each animal were randomly assigned to one of three treatments: injection of autologous bone marrow-derived cells into wound margins (BI), topical application of bone marrow-derived cells over the wound surface (BT) or 5 per cent povidone iodine solution (PI) (control). Wounds were observed for 28 days for granulation tissue formation, wound contraction, histomorphological and histochemical evaluation, and time to complete healing. The mean (se) time to appearance of granulation tissue was significantly less in BI-treated wounds (3.22 [0.22] days) than the BT-treated (3.89 [0.40] days) and PI-treated (4.89 [0.47] days) groups. On days 14 and 21 after surgery, wound contraction was significantly (P<0.05) higher in BI-treated wounds (73.00 and 97.35 per cent) than in those treated with BT (58.75 and 84.87 per cent) and PI (54.84 and 84.60 per cent). Histomorphological findings showed an earlier disappearance of inflammatory reaction, better epithelialisation, significantly more neovascularisation, more fibroplasia and collagenation, and earlier histological maturation in BI- and BT-treated wounds than in control wounds.
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Affiliation(s)
- B M Borena
- Division of Surgery, Indian Veterinary Research Institute, Izatnagar 243122 (UP), India
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Makrilia N, Kollias A, Manolopoulos L, Syrigos K. Cell adhesion molecules: role and clinical significance in cancer. Cancer Invest 2009; 27:1023-37. [PMID: 19909018 DOI: 10.3109/07357900902769749] [Citation(s) in RCA: 242] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
There is a growing body of evidence suggesting that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Indeed, changes in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression, including detachment of tumor cells from the primary site, intravasation into the blood stream, extravasation into distant target organs, and formation of the secondary lesions. This review presents recent data regarding the role of cell adhesion molecules in tumor development and progress with concern to their clinical exploitation as potential biomarkers in neoplastic diseases.
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Affiliation(s)
- Nektaria Makrilia
- Oncology Unit, 3rd Department of Medicine, Sotiria General Hospital, Athens School of Medicine, Greece
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Sengupta N, Caballero S, Sullivan SM, Chang LJ, Afzal A, Li Calzi S, Kielczewski JL, Prabarakan S, Ellis EA, Moldovan L, Moldovan NI, Boulton ME, Grant MB, Scott EW, Harris JR. Regulation of adult hematopoietic stem cells fate for enhanced tissue-specific repair. Mol Ther 2009; 17:1594-604. [PMID: 19584817 PMCID: PMC2835259 DOI: 10.1038/mt.2009.145] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Accepted: 06/01/2009] [Indexed: 12/29/2022] Open
Abstract
The ability to control the differentiation of adult hematopoietic stem cells (HSCs) would promote development of new cell-based therapies to treat multiple degenerative diseases. Systemic injection of NaIO(3) was used to ablate the retinal pigment epithelial (RPE) layer in C57Bl6 mice and initiate neural retinal degeneration. HSCs infected ex vivo with lentiviral vector expressing the RPE-specific gene RPE65 restored a functional RPE layer, with typical RPE phenotype including coexpression of another RPE-specific marker, CRALBP, and photoreceptor outer segment phagocytosis. Retinal degeneration was prevented and visual function, as measured by electroretinography (ERG), was restored to levels similar to that found in normal animals. None of the controls (no HSCs, HSCs alone and HSCs infected with lentiviral vector expressing LacZ) showed these effects. In vitro gene array studies demonstrated that infection of HSC with RPE65 increased adenylate cyclase mRNA. In vitro exposure of HSCs to a pharmacological agonist of adenylate cyclase also led to in vitro differentiation of HSCs to RPE-like cells expressing pigment granules and the RPE-specific marker, CRALBP. Our data confirm that expression of the cell-specific gene RPE65 promoted fate determination of HSCs toward RPE for targeted tissue repair, and did so in part by activation of adenylate cyclase signaling pathways. Expression by HSCs of single genes unique to a differentiated cell may represent a novel experimental paradigm to influence HSC plasticity, force selective differentiation, and ultimately lead to identification of pharmacological alternatives to viral gene delivery.
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Affiliation(s)
- Nilanjana Sengupta
- Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610-0267, USA
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Jeffery R, Poulsom R, Alison MR. Sources of adult hepatic stem cells: haematopoietic. Methods Mol Biol 2009; 481:141-54. [PMID: 19096804 DOI: 10.1007/978-1-59745-201-4_12] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Bone marrow cells can engraft in the liver and differentiate into a variety of cell types including hepatocytes and myofibroblasts. This chapter describes how, after transplantation of male bone marrow into female recipients, cells of bone marrow origin (male) can be identified in the female liver by virtue of detection of the Y chromosome by the technique of in situ hybridisation (ISH). Furthermore, ISH for Y chromosome detection can be combined both with immunohistochemistry (IHC) to identify phenotype and with ISH for mRNA to demonstrate function. Additionally, we show that bone marrow-derived cells can be identified in the liver without prior sex-mismatch bone marrow transplantation, identifying instead the BCR:ABL fusion gene that is present in all such cells in almost all patients suffering from chronic myelogenous leukaemia (CML).
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Affiliation(s)
- Rosemary Jeffery
- Histopathology Unit, Cancer Research UK, London Research Institute, London, UK
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Karaoglu S, Celik C, Korkusuz P. The effects of bone marrow or periosteum on tendon-to-bone tunnel healing in a rabbit model. Knee Surg Sports Traumatol Arthrosc 2009; 17:170-8. [PMID: 18941736 DOI: 10.1007/s00167-008-0646-3] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2007] [Accepted: 09/19/2008] [Indexed: 12/29/2022]
Abstract
The purpose of this study was to investigate whether a grafting technique using either periosteum or bone marrow as an adjunct, would reconstitute more favorable tendon anchorage morphology with improved tensile strength in a bone tunnel model. We hypothesized that autogenous bone marrow aspirate can enhance the tendon-bone attachment as well as a freshly harvested periosteum, because both tissues contain pluripotent cells. Thirty-six skeletally mature New Zealand white rabbits were utilized. For the tendon graft healing in a bone tunnel model, the extensor digitorum longus tendon was detached from its femoral insertion and transplanted through a bone tunnel into the proximal tibia. Three groups were compared. For the group P (periosteum), a periosteum-wrapped tendon was fixed into the tunnel through the proximal tibial metaphysis. For the group BM (bone marrow), instead of periosteum augmentation, fresh bone marrow was injected into the tendon graft that would sit inside the tunnel. For the group C (control), the limb underwent a similar operation with neither the periosteum enveloping nor bone marrow injecting the tendon. At 6 and 12 weeks after surgery, two rabbits were used for light and electron microscopic examinations, and ten rabbits were used for biomechanical tests in each group. The interface tissue between bone and tendon was thicker and less organized in group C compared to groups P and BM at 6 weeks. Ultra-structurally, the interface tissue was loosely organized in group C, compared to others. Bone ingrowth into tendon was more obvious in groups P and BM, compared to group C. The proliferation of cartilage islands was observed within bone tunnels of both groups P and BM; but a well-defined fibrocartilage zone was noted only in group BM at the interface at week 12. Biomechanical findings: (1) at 6 weeks, the average failure load of group P was significantly higher than the others (P < 0.01). At same time point, in terms of stiffness, while group P was significantly higher than the other groups (P < 0.01), group BM was also significantly higher than that of group C (P < 0.05); (2) at 12 weeks, in terms of failure loads, there was a statistical significant difference only between groups BM and C (P < 0.05). At the same time point, stiffness values were not statistically different among the three groups. Based on the histological and biomechanical findings, the present study demonstrated that periosteum had a positive effect when compared to bone marrow and control groups on the tendon-to-bone healing at an early time point (6 weeks), and bone marrow was also effective at 12 weeks time point compared to the control group in an extra-articular bone tunnel in rabbits. The presence of pluripotent cells in both the bone marrow and the periosteum may be the possible mechanism for enhanced healing. Periosteum had a positive effect at an early time point (6 weeks). Bone marrow was more effective at 12 weeks. Therefore, it is possible that a combination of wrapping periosteum and injecting bone marrow to the tendon graft would have a synergistic effect (early and strong). To prove this hypothesis, future studies which would combine both methods are needed.
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Affiliation(s)
- Sinan Karaoglu
- Department of Orthopedics and Traumatology, Faculty of Medicine, Erciyes University, Kayseri 38039, Turkey.
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Abstract
Mesenchymal stem cells (MSCs) have the potential to play a role in autologous repair of central nervous system injury or disease, circumventing both the complications associated with immune rejection of allogenic cells, and many of the ethical concerns associated with embryonic stem cell use. Human bone marrow-derived MSCs can be extracted relatively simply from the marrow of adult patients and maintained and expanded in culture. More importantly, it has been previously demonstrated that MSCs have the capacity to differentiate into neurons and glia in vitro when grown under appropriate conditions. Multipotent MSCs have also been successfully used in transplantation studies in animal models of disease as diverse as demyelination, stroke, trauma and Parkinson's disease. MSCs therefore provide an attractive and practical source of stem cells for reparative therapy in patients, and in this paper we describe methods for the reproducible culture and neural differentiation of human MSCs generated from patient marrow.
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Affiliation(s)
- David Gordon
- University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK
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