ABSTRACT
Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14-CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature ("cluster 6") that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.
Subject(s)
Cell Differentiation , Myeloid-Derived Suppressor Cells , Neutrophils , Proteomics , Humans , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/cytology , Neutrophils/metabolism , Neutrophils/cytology , Proteomics/methods , HL-60 Cells , Cell LineABSTRACT
Three-dimensional (3D) printing technologies open up new perspectives for customizing the external shape and internal architecture of bone scaffolds. In this study, an oligopeptide (SSVPT, Ser-Ser-Val-Pro-Thr) derived from bone morphogenetic protein 2 was conjugated with a dopamine coating on a 3D-printed poly(lactic acid) (PLA) scaffold to enhance osteogenesis. Cell experiments in vitro showed that the scaffold was highly osteoconductive to the adhesion and proliferation of rat marrow mesenchymal stem cells (MSCs). In addition, RT-PCR analysis showed that the scaffold was able to promote the expression of osteogenesis-related genes, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and osteopontin (OPN). Images of the micro-CT 3D reconstruction from the rat cranial bone defect model showed that bone regeneration patterns occurred from one side edge towards the center of the area implanted with the prepared biomimetic peptide hydrogels, demonstrating significantly accelerated bone regeneration. This work will provide a basis to explore the application potential of bioactive scaffolds further.
Subject(s)
Oligopeptides/administration & dosage , Osteogenesis/drug effects , Osteogenesis/physiology , Tissue Scaffolds/chemistry , Alkaline Phosphatase/metabolism , Amino Acid Sequence , Animals , Biocompatible Materials/chemistry , Biomimetic Materials/administration & dosage , Biomimetic Materials/chemistry , Bone Morphogenetic Protein 2/chemistry , Bone Regeneration/drug effects , Bone Regeneration/genetics , Bone Regeneration/physiology , Gene Expression , Immobilized Proteins/administration & dosage , Immobilized Proteins/chemistry , Materials Testing , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Mice , Oligopeptides/chemistry , Osteogenesis/genetics , Polyesters/chemistry , Porosity , Printing, Three-Dimensional , Rats , Rats, Sprague-Dawley , Tissue EngineeringABSTRACT
Polymethylmethacrylate (PMMA) bone cement is widely used in repair of vertebral fracture because of its good biomechanical properties and fast curing. However, the bioinertness of PMMA cement may cause interfacial loosening, fatigue, fracture, and ultimate failure. In this study, biphasic calcium phosphate (BCP) is introduced into PMMA cement to prepare an injectable composite bone cement (BCPx /PMMA) and the content of BCP is optimized to achieve appropriate rate of absorption that matches the bone regeneration. The compressive strength of BCPx /PMMA bone cement is found to comply with the International Standardization Organization standard 5833, and can promote biomineralization as well as adhesion, proliferation, and osteogenic differentiation of Sprague-Dawley rat bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo test performed on a rabbit radius defect model demonstrates that the presence of BCP can significantly improve the osteogenic efficacy of PMMA cement. Therefore, it is anticipated that BCPx /PMMA bone cement, as a promising injectable biomaterial, is of great potential in bone tissue regeneration.
