Interleukins Profiling in Umbilical Cord Mesenchymal Stem Cell-Derived Secretome

Abstract

Background Umbilical cord mesenchymal stem cells (UC-MSCs)-derived secretome is currently used in regenerative therapy. MSCs are believed to secrete a wide spectrum of bioactive molecules which give paracrine effects in immunomodulation and regenerative capacities. One group that was found in secretome is interleukins (ILs), a cytokine that plays an essential role in the process of proliferation, differentiation, maturation, migration, and adhesion of immune cells. However, as there are many types of ILs, the profile of ILs in the UC-MSCs-derived secretome has been limitedly reported. Therefore, in this study, we would like to profile and detect the interleukin concentration secreted by UC-MSCs. Methods UC-MSCs-derived secretome was collected from UC-MSCs passage 5 after 24- and 48-hour incubation (n=9). Secretome was filtered using 0.2 µm and stored at −80°C for further detection. All samples were normalized before the interleukin (IL-2, IL-4, IL-6, IL-9, IL-10, IL-12, IL-17A) detection using a MACSPlex Cytokine Kit. Results The IL-6 has the highest concentration among other interleukins in both groups and increases significantly ( p <0.003) after incubation for 48 hours. The pro-inflammatory factors are decreasing while anti-inflammatory factors are increasing after 48-hour incubation. Discussion Our studies show that the UC-MSCs secrete pro- and anti-inflammatory interleukins. The concentration of anti-inflammatory interleukins shows to be increasing, while the pro-inflammatory interleukins are decreasing within the longer incubation time, but this not be applicable for IL-10 and IL-6. IL-6 has the highest concentration among other ILs. These results may provide important clues regarding when is the right time for secretome to be used in therapy patients, because all the molecules in the secretome can lead to many clinical manifestations.

Treatment of Equine Tarsus Long Medial Collateral Ligament Desmitis with Allogenic Synovial Membrane Mesenchymal Stem/Stromal Cells Enhanced by Umbilical Cord Mesenchymal Stem/Stromal Cell-Derived Conditioned Medium: Proof of Concept

“…Additionally, the UC-MSC secretome is characterized by the presence of angiogenic factors, reduced levels of metalloproteinases (MMPs), and elevated synthesis of transforming growth factor β 1 (TGF-β1), chemokines, and anti-inflammatory cytokines, with interleukyn-6 (IL-6) being one of the most secreted. These characteristics suggest that the UC-MSC secretome presents the ability to control inflammatory responses [32,33].…”

Secretome as a Tool to Treat Neurological Conditions: Are We Ready?

“…After cleavage, mediated by metalloproteinases, this protein functions as an antagonist of chemotaxis and cell activation [32]. Pro-inflammatory cytokines such as IL1b, IL8 [11,12], IL6, IL-1a, interferon (IFN)-γ, and tumor necrosis factor α (TNFα) [33] and IL-9 [35] were also found in the secretome.…”

A Response to Article “Hypoxia Effects in Intervertebral Disc-Derived Stem Cells and Discus Secretomes: An in vitro Study” [Letter]

“… 3–5 Upregulation of pro and anti-inflammatory cytokines and chemokines can certainly be used as immunomodulators. 5 Increased neurotrophic factor would be very beneficial for nerve cell regeneration. 3 …”

“…Characterization of stem cells could provide information about the type of stem cells that produced these growth factors (FGF, PDGF, VEGF, and TGF-β1).Other studies have reported that cytokines and growth factors secretion from MSCs originating from gingival, adipose tissue, umbilical cord or Wharton's jelly tend to increase in a hypoxic microenvironment. [3][4][5] Upregulation of pro and anti-inflammatory cytokines and chemokines can certainly be used as immunomodulators. 5 Increased neurotrophic factor would be very beneficial for nerve cell regeneration.…”

“…[3][4][5] Upregulation of pro and anti-inflammatory cytokines and chemokines can certainly be used as immunomodulators. 5 Increased neurotrophic factor would be very beneficial for nerve cell regeneration. 3 More information about the sources of stem cells, and the methods of obtaining the secretome containing cytokines, chemokines, and growth factors, they would be very useful as evidence for translational research from in vitro and preclinical research toward clinical trial settings.…”