Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Burand, Anthony J.; Di, Lin; Boland, Lauren K.; Boyt, Devlin; Schrodt, Michael V.; Santillan, Donna A.; Ankrum, James A.

doi:10.3389/fimmu.2020.00143

Cited by 31 publications

(40 citation statements)

References 54 publications

(73 reference statements)

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“…Although there is some evidence that 3D cultivation as spheroids can reduce the anti-inflammatory and immunomodulatory potential of MSCs [ 98 ], most secretomes produced by MSCs cultivated in 3D hydrogels seem to have higher anti-inflammatory and immunomodulatory properties, and an overall greater regenerative potential compared to both spheroids and conventionally cultivated cells.…”

Section: Impact Of 3d Cell Culture On Bone Regeneration-relevant Propmentioning

confidence: 99%

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

2021

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As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.

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Section: Impact Of 3d Cell Culture On Bone Regeneration-relevant Propmentioning

confidence: 99%

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

2021

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“…These findings were confirmed with the use of a CD73 enzyme inhibitor (adenosine 5′‐(α, β‐methylene) diphosphate [APCP]), which decreased the Ado production and led to a statistically significant reduction in MSC migration capability compared to control. Curiously, a recent study also demonstrated that the aggregation of MSCs into spheroids causes a significant reduction in the expression and activity of the CD73 enzyme compared to adherent MSCs 115 . Indeed, this role of the CD73 enzyme as an adhesion molecule and consequently involved in cell migration was already suggested for other cell types 39,116 .…”

Section: Adenosinergic Signaling In Proliferation Migration and Homing Of Mscsmentioning

confidence: 94%

“…Indeed, the use of P1 receptor inhibitors, such as caffeine (nonselective), ZM241385, or SCH58261 (A2 A R antagonist) restored the T‐lymphocyte proliferation 21,143,193,194 . However, Burand et al 115 recently showed that the in vitro cell culture method can influence the MSC's immunosuppressive role. In this study, they observed that human MSCs aggregated into spheroids lose the ability to suppress activated T cell proliferation due to reduced expression and activity of the CD73 enzyme 115 …”

Section: Adenosinergic Signaling In Immunomodulatory Effects Of Mscsmentioning

confidence: 99%

“…However, Burand et al 115 recently showed that the in vitro cell culture method can influence the MSC's immunosuppressive role. In this study, they observed that human MSCs aggregated into spheroids lose the ability to suppress activated T cell proliferation due to reduced expression and activity of the CD73 enzyme 115 …”

Section: Adenosinergic Signaling In Immunomodulatory Effects Of Mscsmentioning

confidence: 99%

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The adenosinergic pathway in mesenchymal stem cell fate and functions

Galgaro

Beckenkamp

Nunnenkamp

et al. 2021

Medicinal Research Reviews

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Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis and damage repair through their ability to differentiate into cells of different tissues, trophic support, and immunomodulation. These properties made them attractive for clinical applications in regenerative medicine, immune disorders, and cell transplantation. However, despite multiple preclinical and clinical studies demonstrating beneficial effects of MSCs, their native identity and mechanisms of action remain inconclusive. Since its discovery, the CD73/ecto‐5′‐nucleotidase is known as a classic marker for MSCs, but its role goes far beyond a phenotypic characterization antigen. CD73 contributes to adenosine production, therefore, is an essential component of purinergic signaling, a pathway composed of different nucleotides and nucleosides, which concentrations are finely regulated by the ectoenzymes and receptors. Thus, purinergic signaling controls pathophysiological functions such as proliferation, migration, cell fate, and immune responses. Despite the remarkable progress already achieved in considering adenosinergic pathway as a therapeutic target in different pathologies, its role is not fully explored in the context of the therapeutic functions of MSCs. Therefore, in this review, we provide an overview of the role of CD73 and adenosine‐mediated signaling in the functions ascribed to MSCs, such as homing and proliferation, cell differentiation, and immunomodulation. Additionally, we will discuss the pathophysiological role of MSCs, via CD73 and adenosine, in different diseases, as well as in tumor development and progression. A better understanding of the adenosinergic pathway in the regulation of MSCs functions will help to provide improved therapeutic strategies applicable in regenerative medicine.

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“…In general, the immunomodulatory effect of multipotent MSC, either preconditioned with inflammatory cytokines or apoptotic, metabolically inactivated or even fragmented cells, is transmitted via a variety of secreted cytokines or factors, and surface molecules ( Table 1 ) [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. As a consequence, MSC have the ability to interact and change the functional properties of diverse host immune cells, either from the innate or the adaptive immune system ( Table 2 ) [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ,…”

Section: Immunomodulatory Effects Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Potential of Extracellular Vesicle-Associated TSG-6 from Adipose Mesenchymal Stromal Cells in Traumatic Brain Injury

Roura

Monguió‐Tortajada

Munizaga-Larroudé

et al. 2020

IJMS

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Multipotent mesenchymal stromal cells (MSC) represent a promising strategy for a variety of medical applications. Although only a limited number of MSC engraft and survive after in vivo cellular infusion, MSC have shown beneficial effects on immunomodulation and tissue repair. This indicates that the contribution of MSC exists in paracrine signaling, rather than a cell-contact effect of MSC. In this review, we focus on current knowledge about tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) and mechanisms based on extracellular vesicles (EV) that govern long-lasting immunosuppressive and regenerative activity of MSC. In this context, in particular, we discuss the very robust set of findings by Jha and colleagues, and the opportunity to potentially extend their research focus on EV isolated in concentrated conditioned media (CCM) from adipose tissue derived MSC (ASC). Particularly, the authors showed that ASC-CCM mitigated visual deficits after mild traumatic brain injury in mice. TSG-6 knockdown ASC were, then, used to generate TSG-6-depleted CCM that were not able to replicate the alleviation of abnormalities in injured animals. In light of the presented results, we envision that the infusion of much distilled ASC-CCM could enhance the alleviation of visual abnormalities. In terms of EV research, the advantages of using size-exclusion chromatography are also highlighted because of the enrichment of purer and well-defined EV preparations. Taken together, this could further delineate and boost the benefit of using MSC-based regenerative therapies in the context of forthcoming clinical research testing in diseases that disrupt immune system homeostasis.

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Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Cited by 31 publications

References 54 publications

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

The adenosinergic pathway in mesenchymal stem cell fate and functions

Potential of Extracellular Vesicle-Associated TSG-6 from Adipose Mesenchymal Stromal Cells in Traumatic Brain Injury

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