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      Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells

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          Abstract

          Umbilical cord blood (UCB) is a primitive and abundant source of mesenchymal stem cells (MSCs). UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and disorders. Despite the high latent self-renewal and differentiation capacity of these cells, the safety, efficacy, and yield of MSCs expanded for ex vivo clinical applications remains a concern. However, immunomodulatory effects have emerged in various disease models, exhibiting specific mechanisms of action, such as cell migration and homing, angiogenesis, anti-apoptosis, proliferation, anti-cancer, anti-fibrosis, anti-inflammation and tissue regeneration. Herein, we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies, and discuss the concerns regarding the safety and mass production issues in future applications.

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          M Dominici, K Le Blanc, I. Mueller … (2006)
          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            Concise review: the surface markers and identity of human mesenchymal stem cells.

            Feng-Juan Lv, Rocky S Tuan, Kenneth M. C. Cheung … (2014)
            The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments. Markers that associate with the stemness of MSCs await to be elucidated. A number of candidate MSC surface markers or markers possibly related to their stemness have been brought forward so far, including Stro-1, SSEA-4, CD271, and CD146, yet there is a large difference in their expression in various sources of MSCs. The exact identity of MSCs in vivo is not yet clear, although reports have suggested they may have a fibroblastic or pericytic origin. In this review, we revisit the reported expression of surface molecules in MSCs from various sources, aiming to assess their potential as MSC markers and define the critical panel for future investigation. We also discuss the relationship of MSCs to fibroblasts and pericytes in an attempt to shed light on their identity in vivo. © 2014 AlphaMed Press.
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              Human mesenchymal stem cells modulate allogeneic immune cell responses.

              Sudeepta Aggarwal, Mark F. Pittenger (2005)
              Mesenchymal stem cells (MSCs) are multipotent cells found in several adult tissues. Transplanted allogeneic MSCs can be detected in recipients at extended time points, indicating a lack of immune recognition and clearance. As well, a role for bone marrow-derived MSCs in reducing the incidence and severity of graft-versus-host disease (GVHD) during allogeneic transplantation has recently been reported; however, the mechanisms remain to be investigated. We examined the immunomodulatory functions of human MSCs (hMSCs) by coculturing them with purified subpopulations of immune cells and report here that hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (T helper 1 [T(H)1] and T(H)2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature DCs type 1 (DC1) to decrease tumor necrosis factor alpha (TNF-alpha) secretion and mature DC2 to increase interleukin-10 (IL-10) secretion; hMSCs caused T(H)1 cells to decrease interferon gamma (IFN-gamma) and caused the T(H)2 cells to increase secretion of IL-4; hMSCs caused an increase in the proportion of regulatory T cells (T(Regs)) present; and hMSCs decreased secretion of IFN-gamma from the NK cells. Mechanistically, the hMSCs produced elevated prostaglandin E2 (PGE(2)) in co-cultures, and inhibitors of PGE(2) production mitigated hMSC-mediated immune modulation. These data offer insight into the interactions between allogeneic MSCs and immune cells and provide mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation.
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                Author and article information

                Contributors
                Soyoun Um
                Jueun Ha
                Soo Jin Choi
                Wonil Oh
                Hye Jin Jin
                Journal
                Journal ID (nlm-ta): World J Stem Cells
                Journal ID (publisher-id): WJSC
                Title: World Journal of Stem Cells
                Publisher: Baishideng Publishing Group Inc
                ISSN (Electronic): 1948-0210
                Publication date (Print): 26 December 2020
                Publication date (Electronic): 26 December 2020
                Volume: 12
                Issue: 12
                Pages: 1511-1528
                Affiliations
                Research Team for Immune Cell Therapy, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
                Research Team for Osteoarthritis, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
                Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
                Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
                Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea. genny77@ 123456medi-post.co.kr
                Author notes

                Author contributions: Um S and Jin HJ wrote the manuscript; Ha J and Choi SJ and Oh W collected the data and provided the resources. All authors have read and approve the final manuscript.

                Corresponding author: Hye Jin Jin, PhD, Director, Senior Researcher, Biomedical Research Institute, MEDIPOST Co., Ltd., 21, Daewangpangyo-ro 644-gil, Bundang-gu, Seongnam 13494, South Korea. genny77@ 123456medi-post.co.kr

                Article
                Other ID: jWJSC.v12.i12.pg1511
                DOI: 10.4252/wjsc.v12.i12.1511
                PMC ID: 7789129
                PubMed ID: 33505598
                SO-VID: a4d892d7-5160-4251-b56f-a4d073fb123a
                Copyright © ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
                License:

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                Date received : 30 June 2020
                Date revision received : 23 October 2020
                Date accepted : 11 November 2020
                Categories
                Subject: Review

                Keywords: umbilical cord blood,mesenchymal stem cell,stem cell therapy,immunomodulation,regenerative medicine,therapeutic cell manufacturing processing
                Data availability:
                Keywords: umbilical cord blood, mesenchymal stem cell, stem cell therapy, immunomodulation, regenerative medicine, therapeutic cell manufacturing processing

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