A novel, non-genetic, and scalable proprietary method for enhancing anti-inflammatory, and immunomodulatory properties of mesenchymal stromal cells (MSCs) prior to cryopreservation

Cytotherapy ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. S29
Author(s):  
S. Bhatt ◽  
A. Gómez-Aristizábal ◽  
J. Whiteley ◽  
I. Rogers ◽  
S. Viswanathan
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

scholarly journals ID2006 Crosstalk between effector cells of adaptive immunity and mesenchymal stromal cells

2017 ◽  
Vol 4 (S) ◽  
pp. 38
Author(s):  
Aleksandra Gornostaeva
Keyword(s):  
Innate Immunity ◽  
Adaptive Immunity ◽  
Mesenchymal Stromal Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Feedback Loop ◽  
Inflammatory Phenotype ◽  
Innate Immunity Cells ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

Multipotent mesenchymal stromal cells (MSCs) are a perspective tool for regenerative medicine due low immunogenicity and immunomodulation. The "feedback loop" exists in MSC/immune cells relationships, when "inflammatory" stimulation switches immunoregulaton by MSCs. Currently, the most studied effect of allogeneic MSCs on adaptive immunity cells, mainly on T lymphocytes. Studies of the interaction of MSCs and innate immunity cells are much less. "Reverse effects" (the effect of immune cells on MSCs) are virtually not investigated. Initiation of the inflammation occurs with activation of innate immunity cells, that "turns on" immunomodulatory properties. In this regard, the study of the interaction of MSCs and monocytes is particularly relevant. MSCs from human adipose tissue and CD14+monocytes (MNs) from peripheral blood of healthy volunteers were used. To stimulate monocytes conditioned medium (CM) after 72 hours of mixed lymphocyte reaction (MLR) was applied. This CM was enriched with IL-8, INF-gamma and TNF-a.  Optimization of MN activation procedure was performed prior to experiments. CD14+MNs were incubated with different concentration of MLR-CM for a different time. The activation and viability of MNs was evaluated every 24 hours. The overnight exposure of MNs to 3-day 50% CM-MLR was found to be optimum regime. We studied the of MSC/monocyte interaction paying special attention to "feedback loop".  In the presence of activated MNs, MSCs possessed unchanged viability (96%), transmembrane mitochondria potential, ROS level and twice reduced lysosome activity. The cytokine profile in coculture medium was changed significantly. IL-6 and MCP-1 were increased vs monocultures of both cell types. IL-8 was similar to MN monoculture. TNF alpha, MIG, IL-10 were detected as tracers. Elevation of IL-6 and MIG indicates on acquisition of anti-inflammatory phenotype by MSCs. After interaction with MSC, the share of CD69+ MNs (nonspecific marker of early activation) decreased, HLA-DR (MHC class II receptor) increased slightly. A threefold increase in both CD163+ MN’s share and MFI was detected, whereas CD86 antigen was not expressed. The changes in the cytokine profile and the expression of surface markers described above are characteristic of the anti-inflammatory phenotype of monocytes.  Thus, upon interaction MSC exhibited pronounced immunomodulatory properties and shifted the phenotype of monocytes towards the anti-inflammatory. These data indicate on the MSC potential to modulate early stages of inflammation, while retaining their functional state.

scholarly journals The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Maurice A. Canham ◽  
John D. M. Campbell ◽  
Joanne C. Mountford
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Immune Response ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Host Response ◽  
Distress Syndrome ◽  
Graft Versus Host ◽  
Immunomodulatory Properties ◽  
Efficacious Vaccine

Abstract More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.

scholarly journals Phenotypic and Immunomodulatory Properties of Equine Cord Blood-Derived Mesenchymal Stromal Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0122954 ◽  
Author(s):  
Laurence Tessier ◽  
Dorothee Bienzle ◽  
Lynn B. Williams ◽  
Thomas G. Koch
Keyword(s):  
Cord Blood ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immunomodulatory Properties

scholarly journals A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential?

2022 ◽  
Vol 2 ◽  
Author(s):  
Oleh Andrukhov ◽  
Alice Blufstein ◽  
Christian Behm
Keyword(s):  
Vitamin D ◽  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Mesenchymal Stromal Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Health Maintenance ◽  
Immunomodulatory Properties

Antimicrobial defense is an essential component of host-microbial homeostasis and contributes substantially to oral health maintenance. Dental mesenchymal stromal cells (MSCs) possess multilineage differentiation potential, immunomodulatory properties and play an important role in various processes like regeneration and disease progression. Recent studies show that dental MSCs might also be involved in antibacterial defense. This occurs by producing antimicrobial peptides or attracting professional phagocytic immune cells and modulating their activity. The production of antimicrobial peptides and immunomodulatory abilities of dental MSCs are enhanced by an inflammatory environment and influenced by vitamin D3. Antimicrobial peptides also have anti-inflammatory effects in dental MSCs and improve their differentiation potential. Augmentation of antibacterial efficiency of dental MSCs could broaden their clinical application in dentistry.

scholarly journals Effect of extracorporeal shock wave therapy on equine umbilical cord blood mesenchymal stromal cells in vitro

2020 ◽  
Author(s):  
Ramés Salcedo-Jiménez ◽  
Judith Koenig ◽  
Olivia Lee ◽  
Thomas W.G. Gibson ◽  
Pavneesh Madan ◽  
...  
Keyword(s):  
Shock Wave ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Extracorporeal Shock Wave ◽  
Immunomodulatory Properties

AbstractExtracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells and decrease inflammatory and immune-reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation towards the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

Abstract WP88: In a Pro-inflammatory Environment, Mesenchymal Stromal Cells Exert Anti-inflammatory and Pro-angiogenic Effects on Endothelial Cells

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Kaavya Giridhar ◽  
Nikunj Satani ◽  
Bing Yang ◽  
Songmi Lee ◽  
Xiaopei Xi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Anti Inflammatory

Transient ectopic expression of CXCR4 and IL10 enhances in vivo anti-inflammatory potential of human mesenchymal stromal cells

Cytotherapy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. S60
Author(s):  
M. Hervas-Salcedo ◽  
M. Fernandez-Garcia ◽  
M. Hernando-Rodriguez ◽  
Ó. Quintana ◽  
J. Segovia ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ectopic Expression ◽  
Human Mesenchymal Stromal Cells ◽  
Anti Inflammatory

scholarly journals Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2396
Author(s):  
Katarzyna Zielniok ◽  
Anna Burdzinska ◽  
Beata Kaleta ◽  
Radoslaw Zagozdzon ◽  
Leszek Paczek
Keyword(s):  
Real Time ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Real Time Pcr ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
Immunomodulatory Activity ◽  
Peripheral Blood Mononuclear ◽  
Immunomodulatory Properties

The therapeutic potential of mesenchymal stromal cells (MSCs) is largely attributed to their immunomodulatory properties, which can be further improved by hypoxia priming. In this study, we investigated the immunomodulatory properties of MSCs preconditioned with hypoxia-mimetic Vadadustat (AKB-6548, Akebia). Gene expression analysis of immunomodulatory factors was performed by real-time polymerase chain reaction (real-time PCR) on RNA isolated from six human bone-marrow derived MSCs populations preconditioned for 6 h with 40 μM Vadadustat compared to control MSCs. The effect of Vadadustat preconditioning on MSCs secretome was determined using Proteome Profiler and Luminex, while their immunomodulatory activity was assessed by mixed lymphocyte reaction (MLR) and Culturex transwell migration assays. Real-time PCR revealed that Vadadustat downregulated genes related to immune system: IL24, IL1B, CXCL8, PDCD1LG1, PDCD1LG2, HIF1A, CCL2 and IL6, and upregulated IL17RD, CCL28 and LEP. Vadadustat caused a marked decrease in the secretion of IL6 (by 51%), HGF (by 47%), CCL7 (MCP3) (by 42%) and CXCL8 (by 40%). Vadadustat potentiated the inhibitory effect of MSCs on the proliferation of alloactivated human peripheral blood mononuclear cells (PBMCs), and reduced monocytes-enriched PBMCs chemotaxis towards the MSCs secretome. Preconditioning with Vadadustat may constitute a valuable approach to improve the therapeutic properties of MSCs.

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