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      Preconditioning Stem Cells for In Vivo Delivery

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          Abstract

          Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation.

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          Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties.

          Thomas Bartosh, Joni Ylöstalo, Arezoo Mohammadipoor … (2010)
          Previous reports suggested that culture as 3D aggregates or as spheroids can increase the therapeutic potential of the adult stem/progenitor cells referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). Here we used a hanging drop protocol to prepare human MSCs (hMSCs) as spheroids that maximally expressed TNFalpha stimulated gene/protein 6 (TSG-6), the antiinflammatory protein that was expressed at high levels by hMSCs trapped in the lung after i.v. infusion and that largely explained the beneficial effects of hMSCs in mice with myocardial infarcts. The properties of spheroid hMSCs were found to depend critically on the culture conditions. Under optimal conditions for expression of TSG-6, the hMSCs also expressed high levels of stanniocalcin-1, a protein with both antiinflammatory and antiapoptotic properties. In addition, they expressed high levels of three anticancer proteins: IL-24, TNFalpha-related apoptosis inducing ligand, and CD82. The spheroid hMSCs were more effective than hMSCs from adherent monolayer cultures in suppressing inflammatory responses in a coculture system with LPS-activated macrophages and in a mouse model for peritonitis. In addition, the spheroid hMSCs were about one-fourth the volume of hMSCs from adherent cultures. Apparently as a result, larger numbers of the cells trafficked through the lung after i.v. infusion and were recovered in spleen, liver, kidney, and heart. The data suggest that spheroid hMSCs may be more effective than hMSCs from adherent cultures in therapies for diseases characterized by sterile tissue injury and unresolved inflammation and for some cancers that are sensitive to antiinflammatory agents.
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            Mesenchymal stem cells and their potential as cardiac therapeutics.

            Mark F. Pittenger, Bradley Martin (2004)
            Mesenchymal stem cells (MSCs) represent a stem cell population present in adult tissues that can be isolated, expanded in culture, and characterized in vitro and in vivo. MSCs differentiate readily into chondrocytes, adipocytes, osteocytes, and they can support hematopoietic stem cells or embryonic stem cells in culture. Evidence suggests MSCs can also express phenotypic characteristics of endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte cells. When introduced into the infarcted heart, MSCs prevent deleterious remodeling and improve recovery, although further understanding of MSC differentiation in the cardiac scar tissue is still needed. MSCs have been injected directly into the infarct, or they have been administered intravenously and seen to home to the site of injury. Examination of the interaction of allogeneic MSCs with cells of the immune system indicates little rejection by T cells. Persistence of allogeneic MSCs in vivo suggests their potential "off the shelf" therapeutic use for multiple recipients. Clinical use of cultured human MSCs (hMSCs) has begun for cancer patients, and recipients have received autologous or allogeneic MSCs. Research continues to support the desirable traits of MSCs for development of cellular therapeutics for many tissues, including the cardiovascular system. In summary, hMSCs isolated from adult bone marrow provide an excellent model for development of stem cell therapeutics, and their potential use in the cardiovascular system is currently under investigation in the laboratory and clinical settings.
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              The differential adhesion hypothesis: a direct evaluation.

              Ramsey Foty, Malcolm Steinberg (2005)
              The differential adhesion hypothesis (DAH), advanced in the 1960s, proposed that the liquid-like tissue-spreading and cell segregation phenomena of development arise from tissue surface tensions that in turn arise from differences in intercellular adhesiveness. Our earlier measurements of liquid-like cell aggregate surface tensions have shown that, without exception, a cell aggregate of lower surface tension tends to envelop one of higher surface tension to which it adheres. We here measure the surface tensions of L cell aggregates transfected to express N-, P- or E-cadherin in varied, measured amounts. We report that in these aggregates, in which cadherins are essentially the only cell-cell adhesion molecules, the aggregate surface tensions are a direct, linear function of cadherin expression level. Taken together with our earlier results, the conclusion follows that the liquid-like morphogenetic cell and tissue rearrangements of cell sorting, tissue spreading and segregation represent self-assembly processes guided by the diminution of adhesive-free energy as cells tend to maximize their mutual binding. This conclusion relates to the physics governing these morphogenetic phenomena and applies independently of issues such as the specificities of intercellular adhesives.
              Article 0 comments Cited 218 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biores Open Access
                Journal ID (iso-abbrev): Biores Open Access
                Journal ID (publisher-id): biores
                Title: BioResearch Open Access
                Publisher: Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                ISSN (Print): 2164-7844
                ISSN (Electronic): 2164-7860
                Publication date (Print): 01 August 2014
                Publication date PMC-release: 01 August 2014
                Volume: 3
                Issue: 4
                Pages: 137-149
                Affiliations
                [ 1 ]Hydrodynamics Laboratory , CNRS UMR7646, Ecole Polytechnique, Palaiseau, France.
                [ 2 ]Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University , Tallahassee, Florida.
                Author notes
                Address correspondence to: Yan Li, PhD, Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University 2525 Pottsdamer Street, Tallahassee, FL 32310, E-mail: yli@ 123456eng.fsu.edu
                Article
                Publisher ID: 10.1089/biores.2014.0012
                DOI: 10.1089/biores.2014.0012
                PMC ID: 4120806
                PubMed ID: 25126478
                SO-VID: 715efd84-ff4c-4d4e-9d92-53f3bfc77d1d
                Copyright © Copyright 2014, Mary Ann Liebert, Inc.
                History
                Page count
                Figures: 3, Tables: 3, References: 127, Pages: 13
                Categories
                Subject: Comprehensive Review

                Keywords: aggregate formation,encapsulation,hydrogel,preconditioning,stem cells
                Data availability:
                Keywords: aggregate formation, encapsulation, hydrogel, preconditioning, stem cells

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