Large-scale secretome analyses unveil the superior immunosuppressive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells

Islam, Ashraful; Urbárová, Ilona; Bruun, Jack‐Ansgar; Martínez-Zubiaurre, Iñigo

doi:10.22203/ecm.v037a10

Cited by 16 publications

(16 citation statements)

References 41 publications

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“…These data concur with previous studies that have consistently shown MSCs reduce apoptosis and increase proliferation of several cell types [29] . The authors saw no difference in microglial activation overall or regionally; given the key role of MSCs in immunomodulation [8] , this was surprising. As evolving damage from inflammation can last weeks to months, an effect on neuroinflammation from huMSCs may become more apparent in longer-term studies [31] .…”

Section: Discussionmentioning

confidence: 96%

“…In this study, the authors used huMSCs, which have superior anti-inflammatory effects compared with adult MSCs [8] . MSCs have the potential to treat adult diseases such as stroke [25] .…”

Section: Discussionmentioning

confidence: 99%

“…MSCs are attractive because of their low immunogenicity (allowing non-matched allogeneic transplantation), multilineage differentiation and secretome with pluripotent effects of cytokines, chemokines, growth factors and extracellular vesicles, reacting to the needs of the ischemic cerebral environment [7] . Human umbilical cord-derived mesenchymal stromal cells (huMSCs) have a high differentiation potential and superior anti-inflammatory properties compared with MSCs from adult tissues [8] . This, combined with the developmentally active phase of the newborn brain, leads to a high efficiency of huMSCs.…”

Section: Introductionmentioning

confidence: 99%

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Human umbilical cord mesenchymal stromal cells as an adjunct therapy with therapeutic hypothermia in a piglet model of perinatal asphyxia

et al. 2021

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Background: With therapeutic hypothermia (HT) for neonatal encephalopathy, disability rates are reduced, but not all babies benefit. Pre-clinical rodent studies suggest mesenchymal stromal cells (MSCs) augment HT protection. Aims: The authors studied the efficacy of intravenous (IV) or intranasal (IN) human umbilical cordderived MSCs (huMSCs) as adjunct therapy to HT in a piglet model. Methods: A total of 17 newborn piglets underwent transient cerebral hypoxia-ischemia (HI) and were then randomized to (i) HT at 33.5°C 1À13 h after HI (n = 7), (ii) HT+IV huMSCs (30 £ 10 6 cells) at 24 h and 48 h after HI (n = 5) or (iii) HT+IN huMSCs (30 £ 10 6 cells) at 24 h and 48 h after HI (n = 5). Phosphorus-31 and hydrogen-1 magnetic resonance spectroscopy (MRS) was performed at 30 h and 72 h and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)positive cells and oligodendrocytes quantified. In two further piglets, 30 £ 10 6 IN PKH-labeled huMSCs were administered. Results: HI severity was similar between groups. Amplitude-integrated electroencephalogram (aEEG) recovery was more rapid for HT+IN huMSCs compared with HT from 25 h to 42 h and 49 h to 54 h (P 0.05). MRS phosphocreatine/inorganic phosphate was higher on day 2 in HT+IN huMSCs than HT (P = 0.035). Comparing HT+IN huMSCs with HT and HT+IV huMSCs, there were increased OLIG2 counts in hippocampus (P = 0.011 and 0.018, respectively), internal capsule (P = 0.013 and 0.037, respectively) and periventricular white matter (P = 0.15 for IN versus IV huMSCs). Reduced TUNEL-positive cells were seen in internal capsule with HT+IN huMSCs versus HT (P = 0.05). PKH-labeled huMSCs were detected in the brain 12 h after IN administration. Conclusions: After global HI, compared with HT alone, the authors saw beneficial effects of HT+IN huMSCs administered at 24 h and 48 h (30 £ 10 6 cells/kg total dose) based on more rapid aEEG recovery, improved 31 P MRS brain energy metabolism and increased oligodendrocyte survival at 72 h.

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Section: Discussionmentioning

confidence: 96%

“…In this study, the authors used huMSCs, which have superior anti-inflammatory effects compared with adult MSCs [8] . MSCs have the potential to treat adult diseases such as stroke [25] .…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human umbilical cord mesenchymal stromal cells as an adjunct therapy with therapeutic hypothermia in a piglet model of perinatal asphyxia

et al. 2021

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“…These differences involve a different presence of angiogenic factors [68], a lower amount of metalloproteinases (MMPs) [67,69], that could be potentially beneficial in counteracting cartilage hypertrophy and degradation but, also, a lower ECM protein content [69]. On the other hand, the higher production of TGF-β, chemokines and anti-inflammatory cytokines could make the wjMSCs' secretome a perfect candidate to control the inflammatory process [67][68][69][70]. Similarly, EVs and, in particular, exosomes isolated from both wjMSCs and cbMSCs exerted antifibrotic [71,72], antiapoptotic, proliferative [32,73] and immunomodulatory effects [73][74][75] through the delivery to the target cells of several biological factors, including nucleic acids and proteins and, in particular, cytokines [32,73].…”

Section: Secretome Of Cord Blood and Wharton's Jelly Msc For Oa And Rmentioning

confidence: 99%

Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective

Arrigoni

D’Arrigo

Rossella³

et al. 2020

Cells

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The prevalence of arthritic diseases is increasing in developed countries, but effective treatments are currently lacking. The injection of mesenchymal stem cells (MSCs) represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA). However, the majority of clinical approaches based on MSCs are used within an autologous paradigm, with important limitations. For this reason, allogeneic MSCs isolated from cord blood (cbMSCs) and Wharton’s jelly (wjMSCs) gained increasing interest, demonstrating promising results in this field. Moreover, recent evidences shows that MSCs beneficial effects can be related to their secretome rather than to the presence of cells themselves. Among the trophic factors secreted by MSCs, extracellular vesicles (EVs) are emerging as a promising candidate for the treatment of arthritic joints. In the present review, the application of umbilical cord MSCs and their secretome as innovative therapeutic approaches in the treatment of arthritic joints will be examined. With the prospective of routine clinical applications, umbilical cord MSCs and EVs will be discussed also within an industrial and regulatory perspective.

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“…One of the most important features is immunomodulative activity [ 1 , 2 ]. In the case of activation of the inflammatory process, MSCs indirectly interact with all types of cells of the immune system through the secretion of therapeutic factors that show antiapoptotic, angiogenic and immunosuppressive activity [ 3 , 4 ]. Moreover, the MSCs may also interact with the immune system via direct cell-cell contact with every type of immune system cell.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Proinflammatory Cytokines on the Proliferation, Migration and Secretory Activity of Mesenchymal Stem/Stromal Cells (WJ-MSCs) under 5% O2 and 21% O2 Culture Conditions

Wędzińska

Figiel-Dabrowska

Kozłowska

et al. 2021

JCM

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Treatment with Mesenchymal Stem/Stromal Cells (MSCs) in clinical trials is becoming one of the most-popular and fast-developing branches of modern regenerative medicine, as it is still in an experimental phase. The cross-section of diseases to which these cells are applied is very wide, ranging from degenerative diseases, through autoimmune processes and to acute inflammatory diseases, e.g., viral infections. Indeed, now that first clinical trials applying MSCs against COVID-19 have started, important questions concern not only the therapeutic properties of MSCs, but also the changes that might occur in the cell features as a response to the “cytokine storm” present in the acute phase of an infection and capable of posing a risk to a patient. The aim of our study was thus to assess changes potentially occurring in the biology of MSCs in the active inflammatory environment, e.g., in regards to the cell cycle, cell migration and secretory capacity. The study using MSCs derived from Wharton’s jelly (WJ-MSCs) was conducted under two aerobic conditions: 21% O2 vs. 5% O2, since oxygen concentration is one of the key factors in inflammation. Under both oxygen conditions cells were exposed to proinflammatory cytokines involved significantly in acute inflammation, i.e., IFNγ, TNFα and IL-1β at different concentrations. Regardless of the aerobic conditions, WJ-MSCs in the inflammatory environment do not lose features typical for mesenchymal cells, and their proliferation dynamic remains unchanged. Sudden fluctuations in proliferation, the early indicator of potential genetic disturbance, were not observed, while the cells’ migration activity increased. The presence of pro-inflammatory factors was also found to increase the secretion of such anti-inflammatory cytokines as IL-4 and IL-10. It is concluded that the inflammatory milieu in vitro does not cause phenotype changes or give rise to proliferation disruption of WJ-MSCs, and nor does it inhibit the secretory properties providing for their use against acute inflammation.

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Large-scale secretome analyses unveil the superior immunosuppressive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells

Cited by 16 publications

References 41 publications

Human umbilical cord mesenchymal stromal cells as an adjunct therapy with therapeutic hypothermia in a piglet model of perinatal asphyxia

Human umbilical cord mesenchymal stromal cells as an adjunct therapy with therapeutic hypothermia in a piglet model of perinatal asphyxia

Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective

The Effect of Proinflammatory Cytokines on the Proliferation, Migration and Secretory Activity of Mesenchymal Stem/Stromal Cells (WJ-MSCs) under 5% O2 and 21% O2 Culture Conditions

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