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Chen CH, Tsai CC, Wu PT, Wang IK, Yu J, Tsai WB. Modulation of Neural Differentiation through Submicron-Grooved Topography Surface with Modified Polydopamine. ACS APPLIED BIO MATERIALS 2018; 2:205-216. [DOI: 10.1021/acsabm.8b00556] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Cheng-Hung Chen
- Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Rd., Sec. 4, Taipei 106, Taiwan
| | - Ching-Cheng Tsai
- Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Rd., Sec. 4, Taipei 106, Taiwan
| | - Po-Ting Wu
- Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Rd., Sec. 4, Taipei 106, Taiwan
| | - Ing-Kae Wang
- Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, No. 195, Chung Hsing Rd., Sec. 4, Hsinchu 310, Taiwan
| | - Jiashing Yu
- Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Rd., Sec. 4, Taipei 106, Taiwan
| | - Wei-Bor Tsai
- Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Rd., Sec. 4, Taipei 106, Taiwan
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Jahanbazi Jahan-Abad A, Morteza-zadeh P, Sahab Negah S, Gorji A. Curcumin attenuates harmful effects of arsenic on neural stem/progenitor cells. AVICENNA JOURNAL OF PHYTOMEDICINE 2017; 7:376-388. [PMID: 28884087 PMCID: PMC5580875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 12/08/2016] [Accepted: 12/24/2016] [Indexed: 11/02/2022]
Abstract
OBJECTIVE Arsenic, an environmental pollutant, decreases neuronal migration as well as cellular maturation and inhibits the proliferation of neural progenitor cells. Curcumin has been described as an antioxidant and neuroprotective agent with strong therapeutic potential in some neurological disorders. Human adipose-derived stem cells (hADSCs), a source of multipotent stem cells, can self-renew and differentiate into neural cells. The aim of the present study was to investigate the preventive effect of curcumin against arsenic toxic effects on the viability, telomerase activity, and apoptosis of neural stem/progenitor cells (NSPCs) derived from hADSCs. MATERIALS AND METHODS The characteristics of human adipose tissue were identified by immunocytochemistry for surface markers namely, CD105, CD73, and CD90. Using neurosphere assay, hADSCs were differentiated into neuronal cells. To characterize neural cells, expression of nestin, SOX2, MAP2, and GFAP were assessed by immunocytochemistry. Cytotoxicity and viability of NSPCs were evaluated by MTT assay. Reactive oxygen species (ROS) generated by arsenic exposure, were measured and caspase 3/7 activity and caspase-3 processing as well as the telomerase activity were determined. RESULTS The isolated hADSCs positively expressed CD105, CD73, and CD90. Nestin, Sox2, GFAP, and MAP2 were expressed in the neurospheres derived from hADSCs. Curcumin/arsenic co-treatment significantly increased telomerase activity of NSPCs compared to arsenic group. Furthermore, curcumin significantly reduced arsenic-induced apoptosis (via inactivation of caspases) as well as arsenic-associated ROS generation. CONCLUSION Our findings revealed that curcumin has the potential to prevent harmful effects of arsenic on neurogenesis.
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Affiliation(s)
- Ali Jahanbazi Jahan-Abad
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
- Department of Clinical Biochemistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Sajad Sahab Negah
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
- Department of Neuroscience, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Gorji
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
- Department of Neuroscience, Mashhad University of Medical Sciences, Mashhad, Iran
- Epilepsy Research Center, Department of Neurology, and Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany
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Jang H, Bae WJ, Kim SJ, Cho HJ, Yuk SM, Han DS, Youn CS, Kwon EB, Hwang SY, Kim SW. The herbal formula KH-204 is protective against erectile dysfunction by minimizing oxidative stress and improving lipid profiles in a rat model of erectile dysfunction induced by hypercholesterolaemia. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:129. [PMID: 28235412 PMCID: PMC5324223 DOI: 10.1186/s12906-017-1588-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 01/17/2017] [Indexed: 02/06/2023]
Abstract
Background Hypercholesterolaemia (HC) is a major risk factor for ischemic heart disease and is also known to be a risk factor for erectile dysfunction (ED). ED caused by HC is thought to be related to HC-induced oxidative stress damage in the vascular endothelium and erectile tissue. KH-204 is an herbal formula with a strong antioxidant effect. We evaluated the effects of KH-204 on erectile function in a rat model of HC-induced ED. Methods Male Sprague-Dawley rats (6 weeks old) were divided into normal control, high-fat and cholesterol diet (HFC), and HFC with KH-204 treatment (HFC + KH) groups (n = 12 each). Normal control group rats were fed normal chow diet. HFC and HFC + KH group rats were fed high-fat and cholesterol diets and treated with or without daily oral doses of KH-204 for 12 weeks. Subsequently, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured, and lipid profiles, expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase, oxidative stress (8-hydroxy-2-deoxyguanosine), and ratio of smooth muscle cells and collagen fibres were evaluated in the serum and corpora tissue. Results Compared to the HFC group, the HFC + KH group showed statistically significant increases in peak ICP and ICP/MAP ratio, expression of eNOS and nNOS, and ratio of smooth muscle cells and collagen fibres (p < 0.05). The HFC + KH group also showed statistically significant decreases in oxidative stress (p < 0.05). Further the lipid profiles of this group were ameliorated compared to those of the HFC group (p < 0.05). Conclusions The current study shows that the antioxidant and hypolipidemic effects of KH-204 are effective in ameliorating ED by restoring endothelial dysfunction and suggests that KH-204 may be a potential therapeutic agent for ED by correcting the fundamental cause of ED.
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Ji WC, Zhang XW, Qiu YS. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury. World J Exp Med 2016; 6:58-62. [PMID: 27622154 PMCID: PMC4990758 DOI: 10.5493/wjem.v6.i3.58] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 03/30/2016] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
Abstract
Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.
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Jung AR, Kim RY, Kim HW, Shrestha KR, Jeon SH, Cha KJ, Park YH, Kim DS, Lee JY. Nanoengineered Polystyrene Surfaces with Nanopore Array Pattern Alters Cytoskeleton Organization and Enhances Induction of Neural Differentiation of Human Adipose-Derived Stem Cells. Tissue Eng Part A 2016; 21:2115-24. [PMID: 25919423 DOI: 10.1089/ten.tea.2014.0346] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Human adipose-derived stem cells (hADSCs) can differentiate into various cell types depending on chemical and topographical cues. One topographical cue recently noted to be successful in inducing differentiation is the nanoengineered polystyrene surface containing nanopore array-patterned substrate (NP substrate), which is designed to mimic the nanoscale topographical features of the extracellular matrix. In this study, efficacies of NP and flat substrates in inducing neural differentiation of hADSCs were examined by comparing their substrate-cell adhesion rates, filopodia growth, nuclei elongation, and expression of neural-specific markers. The polystyrene nano Petri dishes containing NP substrates were fabricated by a nano injection molding process using a nickel electroformed nano-mold insert (Diameter: 200 nm. Depth of pore: 500 nm. Center-to-center distance: 500 nm). Cytoskeleton and filopodia structures were observed by scanning electron microscopy and F-actin staining, while cell adhesion was tested by vinculin staining after 24 and 48 h of seeding. Expression of neural specific markers was examined by real-time quantitative polymerase chain reaction and immunocytochemistry. Results showed that NP substrates lead to greater substrate-cell adhesion, filopodia growth, nuclei elongation, and expression of neural specific markers compared to flat substrates. These results not only show the advantages of NP substrates, but they also suggest that further study into cell-substrate interactions may yield great benefits for biomaterial engineering.
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Affiliation(s)
- Ae Ryang Jung
- 1 Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea , Seoul, Korea
| | - Richard Y Kim
- 1 Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea , Seoul, Korea
| | - Hyung Woo Kim
- 2 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) , Pohang, Korea
| | - Kshitiz Raj Shrestha
- 1 Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea , Seoul, Korea
| | - Seung Hwan Jeon
- 1 Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea , Seoul, Korea
| | - Kyoung Je Cha
- 2 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) , Pohang, Korea
| | - Yong Hyun Park
- 1 Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea , Seoul, Korea
| | - Dong Sung Kim
- 2 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) , Pohang, Korea
| | - Ji Youl Lee
- 1 Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea , Seoul, Korea
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Drela K, Lech W, Figiel-Dabrowska A, Zychowicz M, Mikula M, Sarnowska A, Domanska-Janik K. Enhanced neuro-therapeutic potential of Wharton's Jelly–derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture. Cytotherapy 2016; 18:497-509. [DOI: 10.1016/j.jcyt.2016.01.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 01/04/2016] [Accepted: 01/09/2016] [Indexed: 01/01/2023]
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The Role of Current Techniques and Concepts in Peripheral Nerve Repair. PLASTIC SURGERY INTERNATIONAL 2016; 2016:4175293. [PMID: 26904282 PMCID: PMC4745297 DOI: 10.1155/2016/4175293] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 09/29/2015] [Accepted: 10/20/2015] [Indexed: 12/22/2022]
Abstract
Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies.
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Differentiation of human breast-milk stem cells to neural stem cells and neurons. Neurol Res Int 2014; 2014:807896. [PMID: 25506428 PMCID: PMC4260437 DOI: 10.1155/2014/807896] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 10/08/2014] [Accepted: 10/20/2014] [Indexed: 12/24/2022] Open
Abstract
Objectives. Human breast milk contains a heterogeneous population of cells that have the potential to provide a noninvasive source of cells for cell therapy in many neurodegenerative diseases without any ethical concern. The objectives of this study were to differentiate the breast milk-derived stem cells (BMDSC) toward neural stem cells and then into the neurons and neuroglia. Materials and Methods. To do this, the BMDSC were isolated from human breast milk and cultured in Dulbecco's modified Eagle medium/F12 (DMEM/F12) containing fibroblast growth factor (bFGF). The cells were then characterized by evaluation of the embryonic and stem cell markers. Then, the cells were exposed to culture medium containing 1% B27 and 2% N2 for 7–10 days followed by medium supplemented with B27, N2, bFGF 10 µg/mL, and endothelial growth factor (EGF) 20 µg/mL. Then, the sphere-forming assay was performed. The spheres were then differentiated into three neural lineages by withdrawing growth factor in the presence of 5% FBS (fetal bovine serum). The immunofluorescence was done for β-tubulin III, O4, and GFAP (glial fibrillary acidic protein). Results. The results indicated that the cells expressed both embryonic and mesenchymal stem cell (MSC) markers. They also showed neurospheres formation that was nestin-positive. The cells were also differentiated into all three neural lineages. Conclusion. The BMDSC can behave in the same way with neural stem cells. They were differentiated into oligodendrocytes, and astrocytes as well as neurons.
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Xu FT, Li HM, Yin QS, Cui SE, Liu DL, Nan H, Han ZA, Xu KM. Effect of ginsenoside Rg1 on proliferation and neural phenotype differentiation of human adipose-derived stem cells in vitro. Can J Physiol Pharmacol 2014; 92:467-75. [PMID: 24873669 DOI: 10.1139/cjpp-2013-0377] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
AIMS To investigate whether ginsenoside Rg1 can promote neural phenotype differentiation of human adipose-derived stem cells (hASCs) in vitro. METHODS hASCs were isolated from lipo-aspirates, and characterized by specific cell markers and multilineage differentiation capacity after culturing to the 3rd passage. Cultured hASCs were treated with neural inductive media alone (group A, control) or inductive media plus 10, 50, or 100 μg/mL ginsenoside Rg1 (groups B, C, and D, respectively). Cell proliferation was assessed by CCK-8 assay. Neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2) levels were measured by Western blot. mRNA levels of growth associated protein-43 (GAP-43), neural cell adhesion molecule (NCAM), and synapsin-1 (SYN-1) were determined by real-time PCR. RESULTS Ginsenoside Rg1 promoted the proliferation of hASCs (groups B, C, and D) and resulted in higher expression of NSE and MAP-2 compared with the control group. Gene expression levels of GAP-43, NCAM, and SYN-1 in the test groups were higher than that in thw control. The results displayed a dose-dependent effect of ginsenoside Rg1 on cell proliferation and neural phenotype differentiation. CONCLUSION This study indicated that ginsenoside Rg1 promotes cell proliferation and neural phenotype differentiation of hASCs in vitro, suggesting a potential use for hASCs in neural regeneration medicine.
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Affiliation(s)
- Fang-Tian Xu
- a Southern Medical University, Guangzhou 510515, China
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Ji W, Hu S, Zhou J, Wang G, Wang K, Zhang Y. Tissue engineering is a promising method for the repair of spinal cord injuries (Review). Exp Ther Med 2013; 7:523-528. [PMID: 24520240 PMCID: PMC3919911 DOI: 10.3892/etm.2013.1454] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 12/10/2013] [Indexed: 12/23/2022] Open
Abstract
Spinal cord injury (SCI) may lead to a devastating and permanent loss of neurological function, which may place a great economic burden on the family of the patient and society. Methods for reducing the death of neuronal cells, inhibiting immune and inflammatory reactions, and promoting the growth of axons in order to build up synapses with the target cells are the focus of current research. Target cells are located in the damaged spinal cord which create a connect with the scaffold. As tissue engineering technology is developed for use in a variety of different areas, particularly the biomedical field, a clear understanding of the mechanisms of tissue engineering is important. This review establishes how this technology may be used in basic experiments with regard to SCI and considers its potential future clinical use.
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Affiliation(s)
- Wenchen Ji
- Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China ; Department of Physiology, College of Medicine, University of Sydney, Sydney 2006, Australia
| | - Shouye Hu
- Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Jiao Zhou
- Department of Surgery, The Third Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China
| | - Gang Wang
- Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Kunzheng Wang
- Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Yuelin Zhang
- Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
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Xu LJ, Xue BX, Chen D, Gao J, Yang DR, Sun CY, Cui Y, Shan YX. Isolation and passage of muscle-derived stem cells from the rat penile corpora cavernosa and induction of differentiation into smooth muscle cells. Cytotechnology 2013; 66:987-94. [PMID: 24242826 DOI: 10.1007/s10616-013-9651-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 09/23/2013] [Indexed: 01/06/2023] Open
Abstract
This study treated the isolation and passage of muscle-derived stem cells (MDSCs) from rat penile corpora cavernosa, detection of stem cell marker expression, observation of their self-renewal and continuous proliferation, and demonstration of their potential to differentiate into smooth muscle cells in co-culture. Muscle-derived stem cells from the rat penile corpora cavernosa were isolated and purified. The expression of stem cell markers Sca-1 and desmin was detected in PP6 cells, thus confirming that the main components of PP6 cells are MDSCs. The expression of Sca-1 and desmin occurred both in PP6 cells and cells at passages 3, 6, and 8, and there was no significant decrease in the expression level with increasing passage number. The growth curves indicated that the cell doubling time was approximately 48 h. The cells entered the stationary phase after approximately 7 days of culture. The proliferative activity of the cells at passage 8 remained unchanged. After 2 days of co-culture with smooth muscle cells, the DAPI-labeled MDSCs tended to exhibit smooth muscle cell morphology and expression of α-SMA was detected. MDSCs exist in the rat penile corpora cavernosa and possess the potential to differentiate into smooth muscle cells. This discovery serves as the basis in view of the potential use of endogenous stem cells for the treatment of erectile dysfunction (ED).
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Affiliation(s)
- Li-Jun Xu
- Department of Urinary Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
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de Girolamo L, Lucarelli E, Alessandri G, Avanzini MA, Bernardo ME, Biagi E, Brini AT, D'Amico G, Fagioli F, Ferrero I, Locatelli F, Maccario R, Marazzi M, Parolini O, Pessina A, Torre ML, Italian Mesenchymal Stem Cell Group. Mesenchymal stem/stromal cells: a new ''cells as drugs'' paradigm. Efficacy and critical aspects in cell therapy. Curr Pharm Des 2013; 19:2459-73. [PMID: 23278600 PMCID: PMC3788322 DOI: 10.2174/1381612811319130015] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Accepted: 12/24/2012] [Indexed: 12/13/2022]
Abstract
Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects.
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Affiliation(s)
- Laura de Girolamo
- Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milano, Italy
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Side-by-side comparison of the biological characteristics of human umbilical cord and adipose tissue-derived mesenchymal stem cells. BIOMED RESEARCH INTERNATIONAL 2013; 2013:438243. [PMID: 23936800 PMCID: PMC3722850 DOI: 10.1155/2013/438243] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Revised: 05/03/2013] [Accepted: 05/07/2013] [Indexed: 12/20/2022]
Abstract
Both human adipose tissue-derived mesenchymal stem cells (ASCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been explored as attractive mesenchymal stem cells (MSCs) sources, but very few parallel comparative studies of these two cell types have been made. We designed a side-by-side comparative study by isolating MSCs from the adipose tissue and umbilical cords from mothers delivering full-term babies and thus compared the various biological aspects of ASCs and UC-MSCs derived from the same individual, in one study. Both types of cells expressed cell surface markers characteristic of MSCs. ASCs and UC-MSCs both could be efficiently induced into adipocytes, osteoblasts, and neuronal phenotypes. While there were no significant differences in their osteogenic differentiation, the adipogenesis of ASCs was more prominent and efficient than UC-MSCs. In the meanwhile, ASCs responded better to neuronal induction methods, exhibiting the higher differentiation rate in a relatively shorter time. In addition, UC-MSCs exhibited a more prominent secretion profile of cytokines than ASCs. These results indicate that although ASCs and UC-MSCs share considerable similarities in their immunological phenotype and pluripotentiality, certain biological differences do exist, which might have different implications for future cell-based therapy.
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Boulland JL, Mastrangelopoulou M, Boquest AC, Jakobsen R, Noer A, Glover JC, Collas P. Epigenetic regulation of nestin expression during neurogenic differentiation of adipose tissue stem cells. Stem Cells Dev 2012; 22:1042-52. [PMID: 23140086 DOI: 10.1089/scd.2012.0560] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Adipose-tissue-derived stem cells (ASCs) have received considerable attention due to their easy access, expansion potential, and differentiation capacity. ASCs are believed to have the potential to differentiate into neurons. However, the mechanisms by which this may occur remain largely unknown. Here, we show that culturing ASCs under active proliferation conditions greatly improves their propensity to differentiate toward osteogenic, adipogenic, and neurogenic lineages. Neurogenic-induced ASCs express early neurogenic genes as well as markers of mature neurons, including voltage-gated ion channels. Nestin, highly expressed in neural progenitors, is upregulated by mitogenic stimulation of ASCs, and as in neural progenitors, then repressed during neurogenic differentiation. Nestin gene (NES) expression under these conditions appears to be regulated by epigenetic mechanisms. The neural-specific, but not muscle-specific, enhancer regions of NES are DNA demethylated by mitogenic stimulation, and remethylated upon neurogenic differentiation. We observe dynamic changes in histone H3K4, H3K9, and H3K27 methylation on the NES locus before and during neurogenic differentiation that are consistent with epigenetic processes involved in the regulation of NES expression. We suggest that ASCs are epigenetically prepatterned to differentiate toward a neural lineage and that this prepatterning is enhanced by demethylation of critical NES enhancer elements upon mitogenic stimulation preceding neurogenic differentiation. Our findings provide molecular evidence that the differentiation repertoire of ASCs may extend beyond mesodermal lineages.
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Affiliation(s)
- Jean-Luc Boulland
- Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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