Large-scale secretome analyses unveil the superior immunosuppresive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells
Mesenchymal stromal cells (MSCs), given their regenerative potential, are being investigated as a potential therapeutic tool for cartilage lesions. MSCs express several bioactive molecules which act in a paracrine fashion to modulate the tissue microenvironment. Yet, little is known about the divergence of these signalling molecules in different MSC populations. The present study investigated secretomes of stromal cells harvested from Hoffa’s fat pad (HFPSCs), synovial membrane (SMSCs), umbilical cord (UCSCs) and cartilage (ACs) by quantitative liquid chromatography-mass spectrometry (LC-MS/MS) proteomics. Also, multiplex protein arrays and functional assays were performed to compare the constitutive immunomodulatory capabilities of different MSCs. Proteins involved in extracellular matrix degradation and inflammation, such as matrix metalloproteinases (MMPs), interleukin (IL)-17 and complement factors, were downregulated in UCSCs as compared to adult cell sources. Additionally, secretion of transforming growth factor (TGF)-β1 and prostaglandin E2 (PGE2) was enhanced in UCSC supernatants. UCSCs were superior in inhibiting peripheral blood mononuclear cell (PBMC) proliferation, migration and cytokine secretion as compared to adult stromal cells. SMSCs significantly suppressed the proliferation of PBMCs only if they were primed with pro-inflammatory cytokines. Although all cell types repressed human leukocyte antigen-DR isotype (HLADR) surface expression and cytokine release by activated macrophages, only UCSCs significantly blocked IL-6 and IL-12 production. Furthermore, UCSCs supernatants increased aggrecan gene expression in twodimensional chondrocyte cultures. The data demonstrated that UCSCs displayed superior anti-inflammatory and immunosuppressive properties than stromal cells from adult tissues. This allogeneic cell source could potentially be considered as an adjuvant therapy for articular cartilage repair.
PublisherAO Research Institute Davos
CitationIslam, A., Urbarova, I., Bruun, J.A. & Martinez-Zubiaurre, I. (2018). Large-scale secretome analyses unveil the superior immunosuppressive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells. European Cells and Materials, 37, 153-174. https://doi.org/10.22203/eCM.v037a10
Showing items related by title, author, creator and subject.
Stromal Expression of MiR-21 Predicts Biochemical Failure in Prostate Cancer Patients with Gleason Score 6 Melbø-Jørgensen, Christian Nordahl; Ness, Nora; Andersen, Sigve; Valkov, Andrey Yurjevich; Dønnem, Tom; Al-Saad, Samer; Kiselev, Yury; Berg, Thomas; Nordby, Yngve; Bremnes, Roy M.; Busund, Lill-Tove; Richardsen, Elin (Journal article; Tidsskriftartikkel; Peer reviewed, 2014)
A gender specific improved survival related to stromal miR-143 and miR-145 expression in non-small cell lung cancer Skjefstad, Kaja Konstanse; Johannessen, Charles; Grindstad, Thea K.W.; Kilvær, Thomas Karsten; Paulsen, Erna Elise; Pedersen, Mona Irene; Dønnem, Tom; Andersen, Sigve; Bremnes, Roy M.; Richardsen, Elin; Al-Saad, Samer; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-04)Micro RNAs (miRNA) are small non-coding RNAs that post-transcriptionally regulate gene expression. Dysregulation of miRNA cluster 143/145 has been reported in several malignancies, but their role in non-small cell lung cancer (NSCLC) remains elusive. This study investigates the prognostic impact of miR-143 and miR-145 in primary tumors and metastatic lymph nodes in NSCLC tissue. Tissue from 553 ...
Islam, Md Ashraful (Doctoral thesis; Doktorgradsavhandling, 2018-10-12)The management of articular cartilage lesions is one of the weighty challenges for orthopaedic surgeons. The use of mesenchymal stem/stromal cells (MSCs) has demonstrated as an alternative cell source for cartilage repair due to their multilineage differentiation potential and hypoimmunogenic properties. Despite the advances in cartilage repair techniques, there is no consensus relating to the most ...