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      Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy

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          Abstract

          Introduction

          Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapies. Human platelet lysate represents an efficient alternative to fetal bovine serum for clinical-scale expansion of MSCs. Different media used in culture processes should maintain the biological characteristics of MSCs during multiple passages. However, bone marrow-derived MSCs and adipose tissue-derived MSCs have not yet been directly compared with each other under human platelet lysate conditions. This study aims to conduct a direct head-to-head comparison of the biological characteristics of the two types of MSCs under human platelet lysate-supplemented culture conditions for their ability to be used in regenerative medicine applications.

          Methods

          The bone marrow- and adipose tissue-derived MSCs were cultured under human platelet lysate conditions and their biological characteristics evaluated for cell therapy (morphology, immunophenotype, colony-forming unit-fibroblast efficiency, proliferation capacity, potential for mesodermal differentiation, secreted proteins, and immunomodulatory effects).

          Results

          Under human platelet lysate-supplemented culture conditions, bone marrow- and adipose tissue-derived MSCs exhibited similar fibroblast-like morphology and expression patterns of surface markers. Adipose tissue-derived MSCs had greater proliferative potential than bone marrow-derived MSCs, while no significantly difference in colony efficiency were observed between the two types of cells. However, bone marrow-derived MSCs possessed higher capacity toward osteogenic and chondrogenic differentiation compared with adipose tissue-derived MSCs, while similar adipogenic differentiation potential wase observed between the two types of cells. There were some differences between bone marrow- and adipose tissue-derived MSCs for several secreted proteins, such as cytokine (interferon-γ), growth factors (basic fibroblast growth factor, hepatocyte growth factor, and insulin-like growth factor-1), and chemokine (stem cell-derived factor-1). Adipose tissue-derived MSCs had more potent immunomodulatory effects than bone marrow-derived MSCs.

          Conclusions

          Adipose tissue-derived MSCs have biological advantages in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory effects, but bone marrow-derived MSCs have advantages in osteogenic and chondrogenic differentiation potential and secreted proteins (stem cell-derived factor-1 and hepatocyte growth factor); these biological advantages should be considered systematically when choosing the MSC source for specific clinical application.

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          Most cited references40

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          Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives.

          Mesenchymal stem cells (MSCs) are one of a few stem cell types to be applied in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair. In addition to their multipotent differentiation potential, a strong paracrine capacity has been proposed as the principal mechanism that contributes to tissue repair. Apart from cytokine/chemokine secretion, MSCs also display a strong capacity for mitochondrial transfer and microvesicle (exosomes) secretion in response to injury with subsequent promotion of tissue regeneration. These unique properties of MSCs make them an invaluable cell type to repair damaged tissues/organs. Although MSCs offer great promise in the treatment of degenerative diseases and inflammatory disorders, there are still many challenges to overcome prior to their widespread clinical application. Particularly, their in-depth paracrine mechanisms remain a matter for debate and exploration. This review will highlight the discovery of the paracrine mechanism of MSCs, regulation of the paracrine biology of MSCs, important paracrine factors of MSCs in modulation of tissue repair, exosome and mitochondrial transfer for tissue repair, and the future perspective for MSC-based therapy.
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            Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy

            Various source-derived mesenchymal stem cells (MSCs) have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM), adipose tissue (AT), and umbilical cord blood-derived MSCs (UCB-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, and paracrine activity. Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence. Since paracrine action is the main action of MSCs, we examined the anti-inflammatory activity of each MSC under lipopolysaccharide (LPS)-induced inflammation. Co-culture of UCB-MSCs with LPS-treated rat alveolar macrophage, reduced expression of inflammatory cytokines including interleukin-1α (IL-1α), IL-6, and IL-8 via angiopoietin-1 (Ang-1). Using recombinant Ang-1 as potential soluble paracrine factor or its small interference RNA (siRNA), we found that Ang-1 secretion was responsible for this beneficial effect in part by preventing inflammation. Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.
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              Optimization of chemically defined cell culture media--replacing fetal bovine serum in mammalian in vitro methods.

              Quality assurance is becoming increasingly important. Good laboratory practice (GLP) and good manufacturing practice (GMP) are now established standards. The biomedical field aims at an increasing reliance on the use of in vitro methods. Cell and tissue culture methods are generally fast, cheap, reproducible and reduce the use of experimental animals. Good cell culture practice (GCCP) is an attempt to develop a common standard for in vitro methods. The implementation of the use of chemically defined media is part of the GCCP. This will decrease the dependence on animal serum, a supplement with an undefined and variable composition. Defined media supplements are commercially available for some cell types. However, information on the formulation by the companies is often limited and such supplements can therefore not be regarded as completely defined. The development of defined media is difficult and often takes place in isolation. A workshop was organised in 2009 in Copenhagen to discuss strategies to improve the development and use of serum-free defined media. In this report, the results from the meeting are discussed and the formulation of a basic serum-free medium is suggested. Furthermore, recommendations are provided to improve information exchange on newly developed serum-free media. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                chunyu327@163.com
                chinastemcells@163.com
                virosome@163.com
                xinxin_yang1980@126.com
                jinglizhao2005@126.com
                ringring12@126.com
                26609642@qq.com
                13811647091@163.com
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                13 April 2015
                13 April 2015
                2015
                : 6
                : 1
                : 55
                Affiliations
                [ ]China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039 China
                [ ]School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000 China
                [ ]Beijing Institute of Life Science Translational Medicine Research Center, Beijing, 100085 China
                [ ]Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Jinan, 250000 China
                [ ]School of Pharmacy, Changchun University of Traditional Chinese Medicine, Changsha, 410208 China
                [ ]Jilin Vocational College of Industry and Technology, Jilin, 132013 China
                [ ]The First Affiliated Hospital, Hebei North University, Zhangjiakou, 075000 China
                [ ]Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050 China
                Article
                66
                10.1186/s13287-015-0066-5
                4453294
                25884704
                7a148ff4-71e6-42f3-a76d-3db58aea10ff
                © Li et al. 2015
                History
                : 12 July 2014
                : 24 November 2014
                : 25 March 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Molecular medicine
                Molecular medicine

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