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      Molecular Profiles of Cell-to-Cell Variation in the Regenerative Potential of Mesenchymal Stromal Cells

      review-article
      1 , 2 ,
      Stem Cells International
      Hindawi

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          Abstract

          Cell-to-cell variation in the regenerative potential of mesenchymal stromal cells (MSCs) impedes the translation of MSC therapies into clinical practice. Cellular heterogeneity is ubiquitous across MSC cultures from different species and tissues. This review highlights advances to elucidate molecular profiles that identify cell subsets with specific regenerative properties in heterogeneous MSC cultures. Cell surface markers and global signatures are presented for proliferation and differentiation potential, as well as immunomodulation and trophic properties. Key knowledge gaps are discussed as potential areas of future research. Molecular profiles of MSC heterogeneity have the potential to enable unprecedented control over the regenerative potential of MSC therapies through the discovery of new molecular targets and as quality attributes to develop robust and reproducible biomanufacturing processes. These advances would have a positive impact on the nascent field of MSC therapeutics by accelerating the development of therapies with more consistent and effective treatment outcomes.

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          Most cited references101

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          Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.

          The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.
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            Indoleamine 2,3 dioxygenase and metabolic control of immune responses.

            Sustained access to nutrients is a fundamental biological need, especially for proliferating cells, and controlling nutrient supply is an ancient strategy to regulate cellular responses to stimuli. By catabolizing the essential amino acid TRP, cells expressing the enzyme indoleamine 2,3 dioxygenase (IDO) can mediate potent local effects on innate and adaptive immune responses to inflammatory insults. Here, we discuss recent progress in elucidating how IDO activity promotes local metabolic changes that impact cellular and systemic responses to inflammatory and immunological signals. These recent developments identify potential new targets for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              THE DEVELOPMENT OF FIBROBLAST COLONIES IN MONOLAYER CULTURES OF GUINEA-PIG BONE MARROW AND SPLEEN CELLS

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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                SCI
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2019
                17 September 2019
                : 2019
                : 5924878
                Affiliations
                1Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana, USA
                2Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
                Author notes

                Academic Editor: Dario Siniscalco

                Author information
                https://orcid.org/0000-0003-4030-3957
                Article
                10.1155/2019/5924878
                6766122
                31636675
                e92863f2-6256-486d-98f7-12c20bf4d34c
                Copyright © 2019 Kim C. O'Connor.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 July 2019
                : 20 August 2019
                Funding
                Funded by: Carol Lavin Bernick Tulane Faculty
                Funded by: National Science Foundation
                Award ID: 1604129
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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