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1
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Fan L, Wei A, Gao Z, Mu X. Current progress of mesenchymal stem cell membrane-camouflaged nanoparticles for targeted therapy. Biomed Pharmacother 2023; 161:114451. [PMID: 36870279 DOI: 10.1016/j.biopha.2023.114451] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 02/17/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
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Affiliation(s)
- Lianlian Fan
- Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun130033, China
| | - Anhui Wei
- Department of Regenerative Medicine, College of Pharmacy, Jilin University, Changchun130021, China
| | - Zihui Gao
- Changchun City Experimental High School, Changchun130117, China
| | - Xupeng Mu
- Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun130033, China.
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Tenchurin TK, Rodina AV, Saprykin VP, Gorshkova LV, Mikhutkin AA, Kamyshinsky RA, Yakovlev DS, Vasiliev AL, Chvalun SN, Grigoriev TE. The Performance of Nonwoven PLLA Scaffolds of Different Thickness for Stem Cells Seeding and Implantation. Polymers (Basel) 2022; 14:polym14204352. [PMID: 36297930 PMCID: PMC9610477 DOI: 10.3390/polym14204352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/24/2022] [Accepted: 10/13/2022] [Indexed: 11/22/2022] Open
Abstract
The 3D reconstruction of 100 μm- and 600 μm-thick fibrous poly-L/L-lactide scaffolds was performed by confocal laser scanning microscopy and supported by scanning electron microscopy and showed that the density of the fibers on the side adjacent to the electrode is higher, which can affect cell diffusion, while the pore size is generally the same. Bone marrow mesenchymal stem cells cultured in a 600 μm-thick scaffold formed colonies and produced conditions for cell differentiation. An in vitro study of stem cells after 7 days revealed that cell proliferation and hepatocyte growth factor release in the 600 μm-thick scaffold were higher than in the 100 μm-thick scaffold. An in vivo study of scaffolds with and without stem cells implanted subcutaneously onto the backs of recipient mice was carried out to test their biodegradation and biocompatibility over a 0-3-week period. The cells seeded onto the 600 μm-thick scaffold promoted significant neovascularization in vivo. After 3 weeks, a significant number of donor cells persisted only on the inside of the 600 μm-thick scaffold. Thus, the use of bulkier matrices allows to prolong the effect of secretion of growth factors by stem cells during implantation. These 600 μm-thick scaffolds could potentially be utilized to repair and regenerate injuries with stem cell co-culture for vascularization of implant.
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Affiliation(s)
| | - Alla V. Rodina
- National Research Centre “Kurchatov Institute”, 123098 Moscow, Russia
| | - Vladimir P. Saprykin
- Natural Sciences Department, Moscow Region State University, 105005 Moscow, Russia
| | - Lada V. Gorshkova
- National Research Centre “Kurchatov Institute”, 123098 Moscow, Russia
| | | | - Roman A. Kamyshinsky
- National Research Centre “Kurchatov Institute”, 123098 Moscow, Russia
- Shubnikov Institute of Crystallography of FSRC “Crystallography and Photonics” RAS, 119333 Moscow, Russia
| | - Dmitry S. Yakovlev
- Russian Quantum Center, Skolkovo, 121205 Moscow, Russia
- Institute of Nano-, Bio-, Information, Cognitive and Socio-Humanistic Sciences and Technologies, Moscow Institute of Physics and Technology, State University, 141707 Dolgoprudny, Russia
| | - Alexander L. Vasiliev
- National Research Centre “Kurchatov Institute”, 123098 Moscow, Russia
- Shubnikov Institute of Crystallography of FSRC “Crystallography and Photonics” RAS, 119333 Moscow, Russia
- Institute of Nano-, Bio-, Information, Cognitive and Socio-Humanistic Sciences and Technologies, Moscow Institute of Physics and Technology, State University, 141707 Dolgoprudny, Russia
- Correspondence: ; Tel.: +7-910-4130115
| | - Sergey N. Chvalun
- National Research Centre “Kurchatov Institute”, 123098 Moscow, Russia
| | - Timofey E. Grigoriev
- National Research Centre “Kurchatov Institute”, 123098 Moscow, Russia
- Institute of Nano-, Bio-, Information, Cognitive and Socio-Humanistic Sciences and Technologies, Moscow Institute of Physics and Technology, State University, 141707 Dolgoprudny, Russia
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Liang Q, Li Q, Ren B, Yin ZQ. Intravenous infusion of small umbilical cord mesenchymal stem cells could enhance safety and delay retinal degeneration in RCS rats. BMC Ophthalmol 2022; 22:67. [PMID: 35144581 PMCID: PMC8832832 DOI: 10.1186/s12886-021-02171-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 11/10/2021] [Indexed: 11/25/2022] Open
Abstract
Background Human umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a promising therapy for the treatment of retinitis pigmentosa (RP). However, intravenously infused cells may be blocked in the lung, increasing the risk of vascular obstruction, which needs to be optimized to further improve safety and efficacy. Methods We derived small UCMSCs (S-UCMSCs) from filtering UCMSCs with a 10-μm filter, and compared with UCMSCs by flow cytometry, directional differentiation culture and transcriptome sequencing. Then the S-UCMSCs and UCMSCs were intravenously infused in the Royal College Surgeons (RCS) rats to evaluate the safety and the efficacy. Results The diameter of S-UCMSCs ranged from 5.568 to 17.231 μm, with an average diameter of 8.636 ± 2.256 μm, which was significantly smaller than that of UCMSCs. Flow cytometry, immunofluorescence and transcriptome sequencing demonstrated that the S-UCMSCs and UCMSCs were the same kind of MSCs, and the S-UCMSCs were more proliferative. After the S-UCMSCs and UCMSCs were intravenously infused into the Royal College of Surgeons (RCS) rats at a dose of 1 × 106 cells/rat, the S-UCMSCs blocked in the lungs were significantly fewer and disappeared more quickly than UCMSCs. The b wave of the flash electroretinogram was improved at 7 d, and the retinal outer nuclear layer thickness was thicker at 7 d and 14 d. The expression level of inflammation was inhibited, and the expression level of neurotrophic factors was upregulated in the retina and serum after transplantation. Conclusions S-UCMSCs intravenous infusion was safer than UCMSCs and could delay retinal degeneration and protect visual function in RCS rats, which may be a preferable therapeutic approach for RP. Supplementary Information The online version contains supplementary material available at 10.1186/s12886-021-02171-3.
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Affiliation(s)
- Qingling Liang
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China. .,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China.
| | - Qiyou Li
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China
| | - Bangqi Ren
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China
| | - Zheng Qin Yin
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China. .,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China.
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4
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Fu H, Wu Y, Yang X, Huang S, Yu F, Deng H, Zhang S, Xiang Q. Stem cell and its derivatives as drug delivery vehicles: an effective new strategy of drug delivery system. ALL LIFE 2021. [DOI: 10.1080/26895293.2021.1967202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Hongwei Fu
- Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
- Guangdong Province Engineering & Technology Research Centre for Topical Precise Drug Delivery System School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Yinan Wu
- Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
- Guangdong Province Engineering & Technology Research Centre for Topical Precise Drug Delivery System School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Xiaobin Yang
- Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
- Guangdong Province Engineering & Technology Research Centre for Topical Precise Drug Delivery System School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Shiyi Huang
- Biopharmaceutical R&D Center of Jinan University & Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, People’s Republic of China
| | - Fenglin Yu
- Biopharmaceutical R&D Center of Jinan University & Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, People’s Republic of China
| | - Hong Deng
- Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
- Guangdong Province Engineering & Technology Research Centre for Topical Precise Drug Delivery System School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Shu Zhang
- Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
- Guangdong Province Engineering & Technology Research Centre for Topical Precise Drug Delivery System School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Qi Xiang
- Biopharmaceutical R&D Center of Jinan University & Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, People’s Republic of China
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Li JN, Li W, Cao LQ, Liu N, Zhang K. Efficacy of mesenchymal stem cells in the treatment of gastrointestinal malignancies. World J Gastrointest Oncol 2020; 12:365-382. [PMID: 32368316 PMCID: PMC7191336 DOI: 10.4251/wjgo.v12.i4.365] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 03/03/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs), which are a kind of stem cell, possess an immune privileged nature, tumour homing features, and multi-lineage differentiation ability. MSCs have been studied in many fields, such as tissue engineering, nervous system diseases, and cancer treatment. In recent years, an increasing number of researchers have focused on the effects of MSCs on various kinds of tumours. However, the concrete anticancer efficacy of MSCs is still controversial. Gastrointestinal (GI) malignancies are the major causes of cancer-related death worldwide. The interactions of MSCs and GI cancer cells in specific conditions have attracted increasing attention. In this review, we introduce the characteristics of MSCs and analyse the effects of MSCs on GI malignancies, including gastric cancer, hepatoma, pancreatic cancer, and colorectal cancer. In addition, we also provide our perspectives on why MSCs may play different roles in GI malignancies and further research directions to increase the treatment efficacy of MSCs on GI malignancies.
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Affiliation(s)
- Jian-Nan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Wei Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Lan-Qing Cao
- Department of Pathology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Ning Liu
- Department of Central Laboratory, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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He J, Chen G, Liu M, Xu Z, Chen H, Yang L, Lv Y. Scaffold strategies for modulating immune microenvironment during bone regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 108:110411. [PMID: 31923946 DOI: 10.1016/j.msec.2019.110411] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 10/21/2019] [Accepted: 11/07/2019] [Indexed: 12/18/2022]
Abstract
Implanted bone scaffolds often fail to successfully integrate with the host tissue because they do not elicit a favorable immune reaction. Properties of bone scaffold not only provide mechanical and chemical signals to support cell adhesion, migration, proliferation and differentiation, but also play a pivotal role in determining the extent of immune response during bone regeneration. Appropriate design parameters of bone scaffold are of great significance in the process of developing a new generation of bone implants. Herein, this article addresses the recent advances in the field of bone scaffolds for immune response, particularly focusing on the physical and chemical properties of bone scaffold in manipulating the host response. Furthermore, incorporation of bioactive molecules and cells with immunoregulatory function in bone scaffolds are also presented. Finally, continuing challenges and future directions of scaffold-based strategies for modulating immune microenvironment are discussed.
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Affiliation(s)
- Jianhua He
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
| | - Guobao Chen
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China
| | - Mengying Liu
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China
| | - Zhiling Xu
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
| | - Hua Chen
- College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, PR China.
| | - Li Yang
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
| | - Yonggang Lv
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, PR China; Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China.
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Kim HG, Yang WS, Hong YH, Kweon DH, Lee J, Kim S, Cho JY. Anti-inflammatory functions of the CDC25 phosphatase inhibitor BN82002 via targeting AKT2. Biochem Pharmacol 2019; 164:216-227. [PMID: 30980807 DOI: 10.1016/j.bcp.2019.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Accepted: 04/08/2019] [Indexed: 11/28/2022]
Abstract
This study presents BN82002 as an anti-inflammatory drug candidate. It was found that BN82002 inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells and peritoneal macrophages that were activated by toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS). BN82002 dose-dependently down-regulated mRNA levels of nitric oxide synthase, tumor necrosis factor-α, and cyclooxygenase-2. The nuclear translocation of nuclear factor (NF)-κB (p65 and p50) was also blocked by BN82002 in RAW265.7 cells stimulated by LPS. According to reporter gene assay performed with NF-κB construct, BN82002 clearly reduced increased level of luciferase activity mediated by transcription factor NF-κB in LPS-treated RAW264.7 cells and in MyD88- and AKT2-overexpressing HEK293 cells. However, BN82002 did not inhibit NF-κB activity in AKT1- or IKKβ-overexpressing HEK293 cells. NF-κB upstream signaling events specifically targeted AKT2 but had no effect on AKT1. The specific target of BN82002 was Tyr-178 in AKT2. BN82002 bound to Tyr-178 and interrupted the kinase activity of AKT2, according to a cellular thermal shift assay analysis of the interaction of BN82002 with AKT2 and an AKT2 mutant (Tyr-178 mutated to Ala; AKT2 Y178A). These results suggest that BN82002 could reduce inflammatory pathway by controlling NF-κB pathway and specifically targeting AKT2.
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Affiliation(s)
- Han Gyung Kim
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Woo Seok Yang
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Yo Han Hong
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Dae-Hyuk Kweon
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jongsung Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea.
| | - Sunggyu Kim
- Research and Business Foundation, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea.
| | - Jae Youl Cho
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea.
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8
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Orozco Morales ML, Marsit NM, McIntosh OD, Hopkinson A, Sidney LE. Anti-inflammatory potential of human corneal stroma-derived stem cells determined by a novel in vitro corneal epithelial injury model. World J Stem Cells 2019; 11:84-99. [PMID: 30842807 PMCID: PMC6397805 DOI: 10.4252/wjsc.v11.i2.84] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 11/01/2018] [Accepted: 01/01/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An in vitro injury model mimicking a corneal surface injury was optimised using human corneal epithelial cells (hCEC). AIM To investigate whether corneal-stroma derived stem cells (CSSC) seeded on an amniotic membrane (AM) construct manifests an anti-inflammatory, healing response. METHODS Treatment of hCEC with ethanol and pro-inflammatory cytokines were compared in terms of viability loss, cytotoxicity, and pro-inflammatory cytokine release, in order to generate the in vitro injury. This resulted in an optimal injury of 20% (v/v) ethanol for 30 s with 1 ng/mL interleukin-1 (IL-1) beta. Co-culture experiments were performed with CSSC alone and with CSSC-AM constructs. The effect of injury and co-culture on viability, cytotoxicity, IL-6 and IL-8 production, and IL1B, TNF, IL6, and CXCL8 mRNA expression were assessed. RESULTS Co-culture with CSSC inhibited loss of hCEC viability caused by injury. Enzyme linked immunosorbent assay and polymerase chain reaction showed a significant reduction in the production of IL-6 and IL-8 pro-inflammatory cytokines, and reduction in pro-inflammatory cytokine mRNA expression during co-culture with CSSC alone and with the AM construct. These results confirmed the therapeutic potential of the CSSC and the possible use of AM as a cell carrier for application to the ocular surface. CONCLUSION CSSC were shown to have a potentially therapeutic anti-inflammatory effect when treating injured hCEC, demonstrating an important role in corneal regeneration and wound healing, leading to an improved knowledge of their potential use for research and therapeutic purposes.
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Affiliation(s)
- Mariana Lizeth Orozco Morales
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, United Kingdom
| | - Nagi M Marsit
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, United Kingdom
| | - Owen D McIntosh
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, United Kingdom
| | - Andrew Hopkinson
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, United Kingdom
| | - Laura E Sidney
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.
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Jacobs FA, van de Vyver M, Ferris WF. Isolation and Characterization of Different Mesenchymal Stem Cell Populations from Rat Femur. Methods Mol Biol 2019; 1916:133-147. [PMID: 30535691 DOI: 10.1007/978-1-4939-8994-2_13] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Purified mesenchymal stem cells (MSCs) may be used for a multitude of applications, from the study of biological processes such as cell division and coordinated gene expression to tissue engineering and regenerative medicine. However, although highly similar, MSCs isolated and purified from different tissues may be biologically different in the ability of the cells to respond to environmental cues that instigate and propagate changes in cell fate such as differentiation, proliferation, apoptosis, and senescence. Selecting which MSC subtype to study may therefore profoundly influence the outcome of the investigation. Here we outline the isolation, purification, and differentiation of three different MSC subtypes derived from various depots within rat bone. These include MSCs from bone marrow, compact bone, and the proximal femur. Osteoblastic and adipogenic differentiation exemplify differences between these cells.
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Affiliation(s)
- Frans Alexander Jacobs
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Mari van de Vyver
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - William Frank Ferris
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
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Yan J, Hou S, Yu Y, Qiao Y, Xiao T, Mei Y, Zhang Z, Wang B, Huang CC, Lin CH, Suo G. The effect of surface charge on the cytotoxicity and uptake of carbon quantum dots in human umbilical cord derived mesenchymal stem cells. Colloids Surf B Biointerfaces 2018; 171:241-249. [DOI: 10.1016/j.colsurfb.2018.07.034] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 06/22/2018] [Accepted: 07/16/2018] [Indexed: 11/15/2022]
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Lang T, Yin Q, Li Y. Progress of Cell-Derived Biomimetic Drug Delivery Systems for Cancer Therapy. ADVANCED THERAPEUTICS 2018. [DOI: 10.1002/adtp.201800053] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Tianqun Lang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica; Chinese Academy of Sciences; 501 Haike Road Shanghai 201203 China
- School of Pharmacy; University of Chinese Academy of Sciences; Beijing 100049 China
| | - Qi Yin
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica; Chinese Academy of Sciences; 501 Haike Road Shanghai 201203 China
- School of Pharmacy; University of Chinese Academy of Sciences; Beijing 100049 China
| | - Yaping Li
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica; Chinese Academy of Sciences; 501 Haike Road Shanghai 201203 China
- School of Pharmacy; University of Chinese Academy of Sciences; Beijing 100049 China
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Guan Q, Li Y, Shpiruk T, Bhagwat S, Wall DA. Inducible indoleamine 2,3-dioxygenase 1 and programmed death ligand 1 expression as the potency marker for mesenchymal stromal cells. Cytotherapy 2018; 20:639-649. [PMID: 29548707 DOI: 10.1016/j.jcyt.2018.02.003] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 02/02/2018] [Accepted: 02/04/2018] [Indexed: 12/21/2022]
Abstract
AIM Establishment of a potency assay in the manufacturing of clinical-grade mesenchymal stromal cells (MSCs) has been a challenge due to issues of relevance to function, timeline and variability of responder cells. In this study, we attempted to develop a potency assay for MSCs. METHODS Clinical-grade bone marrow-derived MSCs were manufactured. The phenotype and immunosuppressive functions of the MSCs were evaluated based on the International Society for Cellular Therapy guidelines. Resting MSCs licensed by interferon (IFN)-γ exposure overnight were evaluated for changes in immune suppression and immune-relevant proteins. The relationship of immune-relevant protein expression with immunosuppression of MSCs was analyzed. RESULTS MSC supressed third-party T-lymphocyte proliferation with high inter-donor and inter-test variability. The suppression of T-lymphocyte proliferation by IFN-γ-licensed MSCs correlated with that by resting MSCs. Many cellular proteins were up-regulated after IFN-γ exposure, including indoleamine 2,3-dioxygenase 1 (IDO-1), programmed death ligand 1 (PD-L1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and bone marrow stromal antigen 2 (BST-2). The expression levels of IDO-1 and PD-L1 on licensed MSCs, not VCAM-1, ICAM-1 or BST-2 on licensed MSCs, correlated with MSC suppression of third-party T-cell proliferation. CONCLUSION A flow cytometry-based assay of MSCs post-IFN-γ exposure measuring expression of intracellular protein IDO-1 and cell surface protein PD-L1 captures two mechanisms of suppression and offers the potential of a relevant, rapid assay for MSC-mediated immune suppression that would fit with the manufacturing process.
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Affiliation(s)
- Qingdong Guan
- Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Canada; Department of Immunology, University of Manitoba, Winnipeg, Canada; Cellular Therapy Laboratory, CancerCare Manitoba, Winnipeg, Canada; The Institute of Clinical Research and Translational Medicine, Gansu Provincial Hospital, Lanzhou, China.
| | - Yun Li
- Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Canada
| | - Tanner Shpiruk
- Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Canada; Cellular Therapy Laboratory, CancerCare Manitoba, Winnipeg, Canada
| | - Swaroop Bhagwat
- Department of Immunology, University of Manitoba, Winnipeg, Canada; Cellular Therapy Laboratory, CancerCare Manitoba, Winnipeg, Canada
| | - Donna A Wall
- Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Canada; Department of Immunology, University of Manitoba, Winnipeg, Canada; Cellular Therapy Laboratory, CancerCare Manitoba, Winnipeg, Canada; Blood and Marrow Transplant/Cellular Therapy, Division of Haematology/Oncology, The Hospital for Sick Children and the University of Toronto, Toronto, Canada.
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Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, van Wijnen AJ, Cool SM. Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine. Stem Cells Transl Med 2017; 6:2173-2185. [PMID: 29076267 PMCID: PMC5702523 DOI: 10.1002/sctm.17-0129] [Citation(s) in RCA: 505] [Impact Index Per Article: 63.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 08/17/2017] [Indexed: 12/13/2022] Open
Abstract
Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185.
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Affiliation(s)
- Rebekah M. Samsonraj
- Glycotherapeutics GroupInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR)Singapore
- Department of Biomedical EngineeringNational University of SingaporeSingapore
- Department of Orthopaedic SurgeryMayo ClinicRochesterMinnesotaUSA
| | - Michael Raghunath
- Department of Biomedical EngineeringNational University of SingaporeSingapore
- Center for Cell Biology and Tissue Engineering, Competence Center for Tissue Engineering and Substance Testing (TEDD)Institute for Chemistry and Biotechnology, ZHAW School of Life Sciences and Facility Management, Zurich University of Applied SciencesSwitzerland
| | - Victor Nurcombe
- Glycotherapeutics GroupInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR)Singapore
| | - James H. Hui
- Department of Orthopaedic Surgery, Yong Loo Lin School of MedicineNational University of SingaporeSingapore
| | | | - Simon M. Cool
- Glycotherapeutics GroupInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR)Singapore
- Department of Orthopaedic Surgery, Yong Loo Lin School of MedicineNational University of SingaporeSingapore
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14
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Zhai Y, Su J, Ran W, Zhang P, Yin Q, Zhang Z, Yu H, Li Y. Preparation and Application of Cell Membrane-Camouflaged Nanoparticles for Cancer Therapy. Theranostics 2017; 7:2575-2592. [PMID: 28819448 PMCID: PMC5558554 DOI: 10.7150/thno.20118] [Citation(s) in RCA: 218] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 04/23/2017] [Indexed: 02/07/2023] Open
Abstract
Cancer is one of the leading causes of death worldwide. Many treatments have been developed so far, although effective, suffer from severe side effects due to low selectivity. Nanoparticles can improve the therapeutic index of their delivered drugs by specifically transporting them to tumors. However, their exogenous nature usually leads to fast clearance by mononuclear phagocytic system. Recently, cell membrane-camouflaged nanoparticles have been investigated for cancer therapy, taking advantages of excellent biocompatibility and versatile functionality of cell membranes. In this review, we summarized source materials and procedures that have been used for constructing and characterizing biomimetic nanoparticles with a focus on their application in cancer therapy.
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Affiliation(s)
- Yihui Zhai
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jinghan Su
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wei Ran
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Pengcheng Zhang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Qi Yin
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Zhiwen Zhang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Haijun Yu
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Yaping Li
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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15
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Zeng Y, Wang L, Zhou Z, Wang X, Zhang Y, Wang J, Mi P, Liu G, Zhou L. Gadolinium hybrid iron oxide nanocomposites for dual T 1- and T 2-weighted MR imaging of cell labeling. Biomater Sci 2016; 5:50-56. [PMID: 27840861 DOI: 10.1039/c6bm00706f] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Tracking of cells in biological systems is critically important for monitoring disease treatment, such as in stem cell therapy. This report prepared new types of biocompatible gadolinium hybrid iron oxide (GdIO) nanocomposites, which demonstrated high sensitivity for dual T1- and T2-weighted magnetic resonance imaging (MRI). The GdIO nanocomposites could efficiently label mesenchymal stem cells (MSCs) by incubation for 24 h at a safe dose, as they did not affect the cell viability, proliferation or differentiation capacity. There was high contrast enhancement in the GdIO-labeled stem cells for dual T1- and T2-weighted MR imaging. In addition, the GdIO nanocomposites were injected into adult mouse lateral ventricles, where cells could be labeled to monitor their biological behaviors by MRI. These GdIO nanocomposites with dual-imaging functions are a good platform for cell labeling and other diagnostic applications.
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Affiliation(s)
- Yun Zeng
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine & Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Liqin Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. and State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
| | - Zijian Zhou
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
| | - Xiaoyong Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
| | - Yang Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
| | - Junqing Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
| | - Peng Mi
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
| | - Gang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
| | - Liming Zhou
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine & Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
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16
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Campos AM, Maciel E, Moreira ASP, Sousa B, Melo T, Domingues P, Curado L, Antunes B, Domingues MRM, Santos F. Lipidomics of Mesenchymal Stromal Cells: Understanding the Adaptation of Phospholipid Profile in Response to Pro-Inflammatory Cytokines. J Cell Physiol 2015; 231:1024-32. [DOI: 10.1002/jcp.25191] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 09/10/2015] [Indexed: 12/22/2022]
Affiliation(s)
- Ana Margarida Campos
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Elisabete Maciel
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Ana S. P. Moreira
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Bebiana Sousa
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Tânia Melo
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Pedro Domingues
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Liliana Curado
- Cell2B Advanced Therapeutics SA; Biocant Park Núcleo 04 Lote 4 A; Cantanhede Portugal
| | - Brígida Antunes
- Cell2B Advanced Therapeutics SA; Biocant Park Núcleo 04 Lote 4 A; Cantanhede Portugal
| | - M. Rosário M. Domingues
- Mass Spectrometry Centre, QOPNA; Department of Chemistry; University of Aveiro; Aveiro Portugal
| | - Francisco Santos
- Cell2B Advanced Therapeutics SA; Biocant Park Núcleo 04 Lote 4 A; Cantanhede Portugal
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Molina ER, Smith BT, Shah SR, Shin H, Mikos AG. Immunomodulatory properties of stem cells and bioactive molecules for tissue engineering. J Control Release 2015; 219:107-118. [PMID: 26307349 DOI: 10.1016/j.jconrel.2015.08.038] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 08/13/2015] [Accepted: 08/19/2015] [Indexed: 02/06/2023]
Abstract
The immune system plays a crucial role in the success of tissue engineering strategies. Failure to consider the interactions between implantable scaffolds, usually containing cells and/or bioactive molecules, and the immune system can result in rejection of the implant and devastating clinical consequences. However, recent research into mesenchymal stem cells, which are commonly used in many tissue engineering applications, indicates that they may play a beneficial role modulating the immune system. Likewise, direct delivery of bioactive molecules involved in the inflammatory process can promote the success of tissue engineering constructs. In this article, we will review the various mechanisms in which modulation of the immune system is achieved through delivered bioactive molecules and cells and contextualize this information for future strategies in tissue engineering.
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Affiliation(s)
- Eric R Molina
- Department of Bioengineering, Rice University, Houston, TX 77030, USA
| | - Brandon T Smith
- Department of Bioengineering, Rice University, Houston, TX 77030, USA
| | - Sarita R Shah
- Department of Bioengineering, Rice University, Houston, TX 77030, USA
| | - Heungsoo Shin
- Department of Bioengineering, Rice University, Houston, TX 77030, USA; Department of Bioengineering, Hanyang University, Seoul 133-791, South Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul 133-791, South Korea.
| | - Antonios G Mikos
- Department of Bioengineering, Rice University, Houston, TX 77030, USA.
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18
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Perbellini F, Carr CA. Uterine cells-an immunoprivileged cell source for therapy-but are they for everyone? J Mol Cell Cardiol 2015; 85:127-30. [PMID: 26027783 DOI: 10.1016/j.yjmcc.2015.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Revised: 05/21/2015] [Accepted: 05/22/2015] [Indexed: 10/23/2022]
Affiliation(s)
| | - Carolyn A Carr
- Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK.
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19
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Zhang L, Su XS, Ye JS, Wang YY, Guan Z, Yin YF. Bone marrow mesenchymal stem cells suppress metastatic tumor development in mouse by modulating immune system. Stem Cell Res Ther 2015; 6:45. [PMID: 25889932 PMCID: PMC4425902 DOI: 10.1186/s13287-015-0039-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 01/21/2015] [Accepted: 03/05/2015] [Indexed: 12/14/2022] Open
Abstract
Introduction Bone marrow mesenchymal stem cells (BMSCs) have been studied extensively because of their potential use in clinical therapy, regenerative medicine, and tissue engineering. However, their application in tumor therapy remains yet in preclinical stage because of the distinct results from different researches and vagueness of their functional mechanism. In this study, the influence of BMSCs on tumor growth was observed and the potential mechanism was investigated. Method Two animal models, H22 ascitogenous hepatoma in BALb/c mouse and B16-F10 pulmonary metastatic melanoma in C57 mouse, were adopted in experience in vivo and treated with BMSCs by intravenous injection. The percentage of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) and IFN-γ+ T cells were observed in peripheral blood (PB) and bone marrow (BM) by Flow Cytometry. BMSCs were co-cultured in vitro with tumor cells and MDSCs in a tumor conditioned medium separately in order to illustrate the mechanism. Results Our results demonstrated that BMSCs treatment caused a delayed tumor growth and a prolonged survival in both tumor models, the homing fraction of BMSCs in BM was 2% - 5% in 24–72 hours after transfusion and the percentage of Gr-1+CD11b+ MDSCs was downregulated in peripheral blood and BM. Meanwhile, IFN-γ+ T lymphocytes in PB increased. In vitro co-culture showed that BMSCs inhibited the induction and proliferation of MDSCs in tumor conditioned medium, whereas they didn’t affect the proliferation of B16-F10 and H22 cells by in vitro co-culture. Both in vivo and in vitro results showed that BMSCs have a systemic suppressive effect on MDSCs. Conclusion Our data suggest that BMSCs has suppressive effect on tumor and is feasible to be applied in cancer treatment. BMSCs inhibiting MDSCs induction and proliferation is likely one of the mechanism.
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Affiliation(s)
- Lei Zhang
- Biomedical Research Center, Affiliated Calmette Hospital of Kunming Medical University, 504 Qing Nian Road, Kunming, Yunnan, 650011, PR China.
| | - Xiao San Su
- Biomedical Research Center, Affiliated Calmette Hospital of Kunming Medical University, 504 Qing Nian Road, Kunming, Yunnan, 650011, PR China.
| | - Jun Song Ye
- Biomedical Research Center, Affiliated Calmette Hospital of Kunming Medical University, 504 Qing Nian Road, Kunming, Yunnan, 650011, PR China.
| | - Yi Yin Wang
- Biomedical Research Center, Affiliated Calmette Hospital of Kunming Medical University, 504 Qing Nian Road, Kunming, Yunnan, 650011, PR China.
| | - Zheng Guan
- Biomedical Research Center, Affiliated Calmette Hospital of Kunming Medical University, 504 Qing Nian Road, Kunming, Yunnan, 650011, PR China.
| | - Yan Feng Yin
- Biomedical Research Center, Affiliated Calmette Hospital of Kunming Medical University, 504 Qing Nian Road, Kunming, Yunnan, 650011, PR China.
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20
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Zhang B, Luo Q, Chen Z, Sun J, Xu B, Ju Y, Song G. Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells. Stem Cell Res 2015; 14:155-64. [PMID: 25633387 DOI: 10.1016/j.scr.2015.01.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 01/09/2015] [Accepted: 01/11/2015] [Indexed: 12/13/2022] Open
Abstract
Bone marrow stromal cells (BMSCs, also broadly known as bone marrow-derived mesenchymal stem cells) are multipotent stem cells that have a self-renewal capacity and multilineage differentiation potential. Mechanical stretching plays a vital role in regulating the proliferation and differentiation of BMSCs. However, little is known about the effects of cyclic stretching on BMSC migration and invasion. In this study, using a custom-made cell-stretching device, we studied the effects of cyclic mechanical stretching on rat BMSC migration and invasion using a Transwell Boyden Chamber. The protein secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was detected by gelatin zymography, and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) was measured by western blot. We found that cyclic mechanical stretching with 10% amplitude at 1Hz frequency for 8h promotes BMSC migration, but reduces BMSC invasion. FAK and ERK1/2 signals were activated in BMSCs after exposure to cyclic stretching. In the presence of the FAK phosphorylation blocker PF573228 or the ERK1/2 phosphorylation blocker PD98059, the cyclic-stretch-promoted migration of BMSCs was completely suppressed. On the other hand, cyclic mechanical stretching reduced the secretion of MMP-2 and MMP-9 in BMSCs, and PF573228 suppressed the cyclic-stretch-reduced secretion of MMP-2 and MMP-9. The decrease of BMSC invasion induced by mechanical stretching is partially restored by PF573228 but remained unaffected by PD98059. Taken together, these data show that cyclic mechanical stretching promotes BMSC migration via the FAK-ERK1/2 signalling pathway, but reduces BMSC invasion by decreasing secretion of MMP-2 and MMP-9 via FAK, independent of the ERK1/2 signal.
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Affiliation(s)
- Bingyu Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China
| | - Qing Luo
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China
| | - Zhe Chen
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China
| | - Jinghui Sun
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China
| | - Baiyao Xu
- Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan
| | - Yang Ju
- Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan
| | - Guanbin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China.
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21
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Lathrop MJ, Sage EK, Macura SL, Brooks EM, Cruz F, Bonenfant NR, Sokocevic D, MacPherson MB, Beuschel SL, Dunaway CW, Shukla A, Janes SM, Steele C, Mossman BT, Weiss DJ. Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma. Cancer Gene Ther 2014; 22:44-54. [DOI: 10.1038/cgt.2014.68] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/08/2014] [Accepted: 10/08/2014] [Indexed: 12/27/2022]
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22
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Li D, Wang N, Zhang L, Hanyu Z, Xueyuan B, Fu B, Shaoyuan C, Zhang W, Xuefeng S, Li R, Chen X. Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor. Stem Cell Res Ther 2014; 4:103. [PMID: 24004644 PMCID: PMC3856604 DOI: 10.1186/scrt314] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 08/02/2013] [Accepted: 08/23/2013] [Indexed: 12/18/2022] Open
Abstract
Introduction The apoptosis and subsequent injury of podocytes plays a pathogenic role in diabetic nephropathy (DN). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and reducing cellular injury. Our previous study found that MSCs could protect kidneys from diabetes-induced injury without obvious engraftment. So we evaluated the effects of human adipose-derived MSCs (hAd-MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms. Methods We used flow cytometry, Western blot and confocal fluorescence microscopy to study podocytic apoptosis and injury induced by HG at 24 hours, 48 hours, and 72 hours in the presence or absence of MSC-conditioned medium (CM). An antibody-based cytokine array was used to identify the mediating factor, which was verified by adding the neutralizing antibody (NtAb) to block its function or adding the recombinant cytokine to the medium to induce its function. Results hAd-MSC-CM reduced podocytic apoptosis in a dose-dependent manner, decreased the expression of podocytic cleaved caspase-3, and prevented the reduced expression and maintained the normal arrangement of podocytic synaptopodin and nephrin. However, human embryonic lung cell (Wi38)-CM failed to ameliorate podocytic apoptosis or injury. Twelve cytokines with concentration ratios (MSC-CM/Wi38-CM) >10-fold were identified. Epithelial growth factor (EGF) was singled out for its known ability to prevent apoptosis. Recombinant human EGF (rhEGF) prevented podocytic apoptosis and injury similarly to hAd-MSC-CM but, upon blockade of EGF, the beneficial effect of hAd-MSC-CM decreased dramatically. Conclusions hAd-MSCs prevent podocytic apoptosis and injury induced by HG, mainly through secreting soluble EG.
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23
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Chung E, Ahn W, Son Y. CXCL5 abundant in the wound fluid at the late phase of wound healing, possibly promoting migration of mesenchymal stem cells and vascular tube formation. Tissue Eng Regen Med 2014. [DOI: 10.1007/s13770-014-0004-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Nicolay NH, Sommer E, Perez RL, Wirkner U, Bostel T, Ho AD, Lahn M, Debus J, Saffrich R, Huber PE. Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation. Strahlenther Onkol 2014; 190:1037-45. [DOI: 10.1007/s00066-014-0686-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 04/28/2014] [Indexed: 10/25/2022]
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25
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Dubon MJ, Byeon Y, Jung N, Son Y, Park KS. Substance P modulates properties of bone marrow-derived mesenchymal stem cells. Tissue Eng Regen Med 2014. [DOI: 10.1007/s13770-014-0012-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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26
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Lu Z, Wang G, Roohani-Esfahani I, Dunstan CR, Zreiqat H. Baghdadite Ceramics Modulate the Cross Talk Between Human Adipose Stem Cells and Osteoblasts for Bone Regeneration. Tissue Eng Part A 2014; 20:992-1002. [DOI: 10.1089/ten.tea.2013.0470] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- ZuFu Lu
- Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, Australia
| | - GuoCheng Wang
- Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, Australia
| | - Iman Roohani-Esfahani
- Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, Australia
| | - Colin R. Dunstan
- Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, Australia
| | - Hala Zreiqat
- Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, Australia
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Abstract
Bronchopulmonary dysplasia (BPD) continues to be a significant cause of morbidity and mortality for premature infants. Currently, most treatment strategies are mainly palliative and do not address the underlying structural changes of the lungs leading to the symptoms. New research and ongoing experiments with mesenchymal stem cells are showing capabilities to mitigate structural damage and promote vascular growth that leads to normal lung architecture in animal models. Looking at the pathophysiology that contributes to BPD and assessing current treatment options available, there still appears to be a gap in treatment that addresses the structural issues within the lungs. This article reviews the findings of several mesenchymal stem cell experiments and the potential for future treatment to help repair the lungs in infants with BPD.
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Yang Y, Yang WS, Yu T, Yi YS, Park JG, Jeong D, Kim JH, Oh JS, Yoon K, Kim JH, Cho JY. Novel anti-inflammatory function of NSC95397 by the suppression of multiple kinases. Biochem Pharmacol 2014; 88:201-15. [PMID: 24468133 DOI: 10.1016/j.bcp.2014.01.022] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 01/11/2014] [Accepted: 01/16/2014] [Indexed: 12/11/2022]
Abstract
NSC95397 (2,3-bis-[(2-hydroxyethyl)thio]-1,4-naphthoquinone) is a CDC25 inhibitor with anti-cancer properties. Since the anti-inflammatory activity of this compound has not yet been explored, the aim of this study was to examine whether this compound is able to modulate the inflammatory process. Toll like receptor (TLR)-mediated inflammatory responses were induced by lipopolysaccharide (LPS), a TLR4 ligand, and pam3CSK, a TLR2 ligand, in peritoneal macrophages and RAW264.7. The molecular mechanism of NSC95397's anti-inflammatory activity was studied using immunoblotting analysis, nuclear fractionation, immunoprecipitation, overexpression strategies, luciferase reporter gene assays, and kinase assays. NSC95397 dose-dependently suppressed the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin (PG)E2, and diminished the mRNA expression of inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, interferon (IFN)-β, and TNF-α in peritoneal macrophages and RAW264.7 cells that were stimulated by LPS and pam3CSK. This compound also clearly blocked the activation of NF-κB (p65), AP-1 (c-Fos/c-Jun), and IRF-3 in LPS-treated RAW264.7 cells and TRIF- and MyD88-overexpressing HEK293 cells. In addition, biochemical and molecular approaches revealed that this compound targeted AKT, IKKα/β, MKK7, and TBK1. Therefore, these results suggest that the anti-inflammatory function of NSC95397 can be attributed to its inhibition of multiple targets such as AKT, IKKα/β, MKK7, and TBK1.
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Affiliation(s)
- Yanyan Yang
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Woo Seok Yang
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Tao Yu
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Young-Su Yi
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Jae Gwang Park
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Deok Jeong
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Ji Hye Kim
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Jeong Su Oh
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Keejung Yoon
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Jong-Hoon Kim
- Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea.
| | - Jae Youl Cho
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
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Nicolay NH, Sommer E, Lopez R, Wirkner U, Trinh T, Sisombath S, Debus J, Ho AD, Saffrich R, Huber PE. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation. Int J Radiat Oncol Biol Phys 2013; 87:1171-8. [DOI: 10.1016/j.ijrobp.2013.09.003] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 08/16/2013] [Accepted: 09/03/2013] [Indexed: 10/26/2022]
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Zou C, Luo Q, Qin J, Shi Y, Yang L, Ju B, Song G. Osteopontin promotes mesenchymal stem cell migration and lessens cell stiffness via integrin β1, FAK, and ERK pathways. Cell Biochem Biophys 2013; 65:455-62. [PMID: 23086356 DOI: 10.1007/s12013-012-9449-8] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The use of mesenchymal stem cells (MSCs) for therapeutic applications has attracted great attention because MSCs home to and engraft to injured tissues after in vivo administration. The expression of osteopontin (OPN) is elevated in response to injury and inflammation, and its role on rat bone marrow-derived mesenchymal stem cells (rMSCs)-directed migration has been elucidated. However, the signaling pathways through the activation of which OPN promotes rMSCs migration and the involvement of cell mechanics during OPN-mediating rMSCs migration have not been well studied. In this study, we found that OPN activated focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) signaling pathways by the ligation of integrin β1 in rMSCs. Inhibitors of FAK and ERK pathways inhibited OPN-induced rMSCs migration, indicating the possible involvement of FAK and ERK activation in OPN-induced migration in rMSCs. In addition, atomic force microscopy analysis showed that OPN reduced cell stiffness in rMSCs via integrin β1, FAK, and ERK pathways, suggesting that the promotion of rMSCs migration might partially be contributing to the decrease in cell stiffness stimulated by OPN. To further examine the role of OPN on cell motility and stiffness, actin cytoskeleton of rMSCs was observed. The reduced well-defined F-actin filaments and the promoted formation of pseudopodia in rMSCs induced by OPN explained the reduction in cell stiffness and the increase in cell migration. The current study data have shown for the first time that OPN binding to integrin β1 promotes rMSCs migration through the activation of FAK and ERK pathways, which may be attributed to the change in cell stiffness caused by the reduction in the amount of organized actin cytoskeleton.
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Affiliation(s)
- Chengyu Zou
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China
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31
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Age-related macular degeneration (AMD): Current concepts in pathogenesis and prospects for treatment. Tissue Eng Regen Med 2013. [DOI: 10.1007/s13770-012-0374-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Liu LN, Wang G, Hendricks K, Lee K, Bohnlein E, Junker U, Mosca JD. Comparison of drug and cell-based delivery: engineered adult mesenchymal stem cells expressing soluble tumor necrosis factor receptor II prevent arthritis in mouse and rat animal models. Stem Cells Transl Med 2013; 2:362-75. [PMID: 23592838 DOI: 10.5966/sctm.2012-0135] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease with unknown etiology where tumor necrosis factor-α (TNFα) plays a critical role. Etanercept, a recombinant fusion protein of human soluble tumor necrosis factor receptor II (hsTNFR) linked to the Fc portion of human IgG1, is used to treat RA based on the rationale that sTNFR binds TNFα and blocks TNFα-mediated inflammation. We compared hsTNFR protein delivery from genetically engineered human mesenchymal stem cells (hMSCs) with etanercept. Blocking TNFα-dependent intercellular adhesion molecule-1 expression on transduced hMSCs and inhibition of nitric oxide production from TNFα-treated bovine chondrocytes by conditioned culture media from transduced hMSCs demonstrated the functionality of the hsTNFR construction. Implanted hsTNFR-transduced mesenchymal stem cells (MSCs) reduced mouse serum circulating TNFα generated from either implanted TNFα-expressing cells or lipopolysaccharide induction more effectively than etanercept (TNFα, 100%; interleukin [IL]-1α, 90%; and IL-6, 60% within 6 hours), suggesting faster clearance of the soluble tumor necrosis factor receptor (sTNFR)-TNFα complex from the animals. In vivo efficacy of sTNFR-transduced MSCs was illustrated in two (immune-deficient and immune-competent) arthritic rodent models. In the antibody-induced arthritis BalbC/SCID mouse model, intramuscular injection of hsTNFR-transduced hMSCs reduced joint inflammation by 90% compared with untransduced hMSCs; in the collagen-induced arthritis Fischer rat model, both sTNFR-transduced rat MSCs and etanercept inhibited joint inflammation by 30%. In vitro chondrogenesis assays showed the ability of TNFα and IL1α, but not interferon γ, to inhibit hMSC differentiation to chondrocytes, illustrating an additional negative role for inflammatory cytokines in joint repair. The data support the utility of hMSCs as therapeutic gene delivery vehicles and their potential to be used in alleviating inflammation within the arthritic joint.
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Affiliation(s)
- Linda N Liu
- Osiris Therapeutics, Inc., Baltimore, MD, USA
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Induction of mesenchymal to epithelial transition of circulating mesenchymal stem cells by conditioned medium of injured cornea. Tissue Eng Regen Med 2013. [DOI: 10.1007/s13770-013-0378-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Gálvez P, Clares B, Hmadcha A, Ruiz A, Soria B. Development of a cell-based medicinal product: regulatory structures in the European Union. Br Med Bull 2013. [PMID: 23184855 DOI: 10.1093/bmb/lds036] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
INTRODUCTION New therapies with genes, tissues and cells have taken the emerging field for the treatment of many diseases. Advances on stem cell therapy research have led to international regulatory agencies to harmonize and regulate the development of new medicines with stem cells. SOURCES OF DATA European Medicines Agency on September 15, 2012. AREAS OF AGREEMENT Cell therapy medicinal products should be subjected to the same regulatory principles than any other medicine. AREAS OF CONTROVERSY Their technical requirements for quality, safety and efficacy must be more specific and stringent than other biologic products and medicines. GROWING POINTS Cell therapy medicinal products are at the cutting edge of innovation and offer a major hope for various diseases for which there are limited or no therapeutic options. AREAS TIMELY FOR DEVELOPING RESEARCH The development of cell therapy medicinal products constitutes an alternative therapeutic strategy to conventional clinical therapy, for which no effective cure was previously available.
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Wong HL, Siu WS, Shum WT, Gao S, Leung PC, Ko CH. Application of Chinese herbal medicines to revitalize adult stem cells for tissue regeneration. Chin J Integr Med 2012; 18:903-8. [PMID: 23238998 DOI: 10.1007/s11655-012-1293-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Indexed: 12/11/2022]
Abstract
It has been established in the recent several decades that adult stem cells play a crucial role in tissue renewal and regeneration. Adult stem cells locate in certain organs can differentiate into functional entities such as macrophages and bone cells. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are two of the most important populations of adult stem cells. The application of these stem cells offers a new insight in treating various pathological conditions, through replenishing cells of specific functions by turning on or off the differentiating program within quiescent stem cell niches. Apart from that, they are also capable to travel through the circulation, migrate to injury sites and differentiate to enhance regeneration process. Recently, Chinese medicine (CM) has shown to be potential candidates to activate adult stem cells for tissue regeneration. This review summarizes our own, as well as others' findings concerning the use of Chinese herbal medicine in the regulation processes of adult stem cells differentiation and their movement in tissue repair and rejuvenation. A number of Chinese herbs are used as therapeutic agents and presumably preventive agents on metabolic disorders. In our opinion, the activation of adult stem cells self-regeneration not only provides a novel way to repair tissue damage, but also reduces the use of targeted drug that adversely altering the normal metabolism of human subjects.
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Affiliation(s)
- Hing-Lok Wong
- Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China
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Jakob M, Hemeda H, Bruderek K, H Gerstner AO, Bootz F, Lang S, Brandau S. Comparative functional cell biological analysis of mesenchymal stem cells of the head and neck region: potential impact on wound healing, trauma, and infection. Head Neck 2012; 35:1621-9. [PMID: 23152157 DOI: 10.1002/hed.23196] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2012] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) are multipotent mesenchymal progenitor cells, originally identified in bone-marrow. Little is known about MSCs of the head and neck region. We investigated cell biological properties with a potential impact on wound healing of 2 different tissue-resident MSC populations. METHODS MSCs were isolated from human nasal mucosa (nmMSCs) and parotid gland (pgMSCs). Clonogenic potential, cell surface markers, cytokine secretion, chemokine receptor expression, mobility, and adhesion to extracellular matrix were examined in unstimulated and stimulated MSCs. RESULTS NmMSCs had the higher clonogenic potential. PgMSCs showed a broader panel of chemokine receptor expression and displayed higher mobility, especially after challenge with bacterial lipopolysaccharide (LPS). NmMSCs were less mobile and showed increased LPS-induced secretion of the inflammatory cytokine interleukin-8 (IL-8) compared with pgMSCs. CONCLUSION These data highlight functional differences between tissue-resident MSCs of the head and neck region, which may impact functional properties of these cells in response to trauma or infection.
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Affiliation(s)
- Mark Jakob
- Department of Otorhinolaryngology, University Hospital Bonn, Bonn, Germany
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Cha HJ, Hwang ES. Current status of biology, bioengineering, and therapeutic potential of stem cells. Arch Pharm Res 2012; 35:193-6. [PMID: 22370773 DOI: 10.1007/s12272-012-0200-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Hyuk-Jin Cha
- College of Natural Sciences, Department of Life Science, Sogang University, Seoul 121-742, Korea
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