Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities

Galipeau, Jacques; Sensebé, Luc

doi:10.1016/j.stem.2018.05.004

Cited by 1,316 publications

(1,190 citation statements)

References 51 publications

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“…MSC have been widely evaluated experimentally and clinically for their ability to stimulate wound healing and suppress inflammation . However, there is comparatively less research regarding the use of MSC for anti‐infective therapy .…”

Section: Discussionsupporting

confidence: 48%

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Chow

Johnson

Impastato

et al. 2019

Stem Cells Translational Medicine

106

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Mesenchymal stem cells (MSC) have been shown to improve wound healing and sup-press inflammatory immune responses. Newer research also indicates that MSC exhibit antimicrobial activity, although the mechanisms underlying this activity have not been fully elucidated. Therefore, we conducted in vitro and in vivo studies to examine the ability of resting and activated MSC to kill bacteria, including multidrug resistant strains. We investigated direct bacterial killing mechanisms and the interaction of MSC with host innate immune responses to infection. In addition, the activity of MSC against chronic bacterial infections was investigated in a mouse biofilm infection model. We found that MSC exhibited high levels of spontaneous direct bactericidal activity in vitro. Moreover, soluble factors secreted by MSC inhibited Staphylococcus aureus biofilm formation in vitro and disrupted the growth of established biofilms. Secreted factors from MSC also elicited synergistic killing of drug-resistant bacteria when combined with several major classes of antibiotics. Other studies demonstrated interactions of activated MSC with host innate immune responses, including triggering of neutrophil extracellular trap formation and increased phagocytosis of bacteria. Finally, activated MSC administered systemically to mice with established S. aureus biofilm infections significantly reduced bacterial numbers at the wound site and improved wound healing when combined with antibiotic therapy. These results indicate that MSC generate multiple direct and indirect, immunologically mediated antimicrobial activities that combine to help eliminate chronic bacterial infections when the cells are administered therapeutically.

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Section: Discussionsupporting

confidence: 48%

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Chow

Johnson

Impastato

et al. 2019

Stem Cells Translational Medicine

106

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“…In parallel to these changes of paradigm regarding the mechanism of action of MSC treatment over the last decade, numerous preclinical studies testing MSCs in a great variety of experimental animal models of immune‐mediated diseases have been carried out, showing in most cases good safety and efficacy results . These encouraging results prompted researchers to test the feasibility, safety, and efficacy of MSCs treatment in human clinical trials in a variety of indications (920 at the start of 2019 according to).…”

Section: Mechanism Of Action; Current State Of the Artmentioning

confidence: 99%

Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era? Concise Review

Hoogduijn

Lombardo²

2019

Stem Cells Translational Medicine

125

118

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Summary 2018 was the year of the first marketing authorization of an allogeneic stem cell therapy by the European Medicines Agency. The authorization concerns the use of allogeneic adipose tissue‐derived mesenchymal stromal cells (MSCs) for treatment of complex perianal fistulas in Crohn's disease. This is a breakthrough in the field of MSC therapy. The last few years have, furthermore, seen some breakthroughs in the investigations into the mechanisms of action of MSC therapy. Although the therapeutic effects of MSCs have largely been attributed to their secretion of immunomodulatory and regenerative factors, it has now become clear that some of the effects are mediated through host phagocytic cells that clear administered MSCs and in the process adapt an immunoregulatory and regeneration supporting function. The increased interest in therapeutic use of MSCs and the ongoing elucidation of the mechanisms of action of MSCs are promising indicators that 2019 may be the dawn of the therapeutic era of MSCs and that there will be revived interest in research to more efficient, practical, and sustainable MSC‐based therapies. Stem Cells Translational Medicine 2019;8:1126–1134

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“…Despite these efforts, the effectiveness of MSCs as a treatment modality for these conditions is still uncertain and market authorizations have been limited. In addition, critical and clear phenotypic parameters for defining MSCs are uncertain and a coherent biological framework surrounding the therapeutic mechanism of action is not yet available . Added to this, cell manufacturing protocols are complex and costly and present substantial challenges in terms of regulatory oversight and standardization .…”

Section: Mscsmentioning

confidence: 99%

MSC Therapy for Osteoarthritis: An Unfinished Story

Barry

2019

Journal Orthopaedic Research

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Mesenchymal stromal cells (MSCs) have firmly occupied the attention of orthopedic clinicians and scientists for most of the last 25 years. Hundreds of laboratories worldwide have carried out research aimed at unraveling the biological characteristics of these cells and probing the manner in which they potentially contribute to cartilage and bone repair. Clinical trials registries indicate that they are also being tested in patient studies for a wide range of conditions such as osteoarthritis, rheumatoid arthritis, fracture repair, regeneration of articular cartilage, tendon repair, and for treatment of degenerative disc disease. Despite these efforts, the effectiveness of MSCs as a treatment modality for these conditions is still uncertain and market authorizations have been limited. In addition, critical and clear phenotypic parameters for defining MSCs are uncertain and a coherent biological framework surrounding the therapeutic mechanism of action is not yet available. Added to this, cell manufacturing protocols are complex and costly and present substantial challenges in terms of regulatory oversight and standardization. Despite these obstacles, MSCs still remain at the forefront of efforts in Regenerative Medicine, based on a conviction that this technology can provide an effective treatment paradigm for major diseases where there is still an unmet need. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1229–1235, 2019.

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Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities

Cited by 1,316 publications

References 51 publications

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era? Concise Review

MSC Therapy for Osteoarthritis: An Unfinished Story

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