Background: This study tested the hypothesis that overexpression of cellular prion protein in endothelial progenitor cells (PrPc-EPCs), defined as "rejuvenated EPCs," was superior to EPCs for salvaging the critical limb ischemia (CLI) induced after 28-day chronic kidney disease (CKD) induction in rat.
Methods And Results: Cell viability and flow cytometric analyses of early/late apoptosis/total-intracellular ROS/cell cycle (sub-G1, G2/M phase) were significantly higher in EPCs + HO than in EPCs that were significantly reversed in PrPc-EPCs + HO (all p < 0.001). The protein expressions of inflammation (IL-1ß/IL-6/MMP-9/p-NF-κB) were significantly increased in EPC + TNF-α than in EPCs that were significantly reversed in PrPc-EPCs + TNF-α (all p < 0.001). Adult-male SD rats (n = 8/each group) were categorized into group 1 (sham-operated control), group 2 (CKD + CLI), group 3 [CKD + CLI + EPCs by intravenous (0.6 × 10)/intra-muscular (0.6 × 10) injections at 3 h after CLI induction], group 4 (CKD + CLI + PrPc-EPCs/dose-administration as group 3) and group 5 (CKD + CLI + siPrnp-EPCs/dose-administration as group 3). By day 14 after CLI induction, the ratio of ischemia to normal blood flow (INBF) in CLI area was highest in group 1/lowest in group 2/significantly higher in group 4 than in groups 3/5 and significantly higher in group 3 than in group 5 (all p < 0.0001). Histopathology demonstrated that the angiogenesis (number of small vessels/CD31 + cells) exhibited a similar trend, whereas the fibrosis/kidney injury score exhibited an opposite pattern of INBF among the groups (all p < 0.0001). The protein expressions of angiogenesis (SDF-1α/VEGF/CXCR4)/cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) were significantly and progressively increased from groups 1-4 that were reversed in group 5 (all p < 0.0001). The protein expressions of fibrotic (p-Smad3/TGF-ß)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/apoptotic (mitochondrial-Bax/cleaved caspase3/cleaved PARP)/mitochondrial-damaged (cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of INBF among the groups (all p < 0.0001).
Conclusion: PrPc-EPCs were superior to EPCs only therapy for salvaging the CLI.
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http://dx.doi.org/10.1186/s13287-022-03119-0 | DOI Listing |
Cell
December 2024
Cell Design Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:
In vitro development relies primarily on treating progenitor cells with media-borne morphogens and thus lacks native-like spatial information. Here, we engineer morphogen-secreting organizer cells programmed to self-assemble, via cell adhesion, around mouse embryonic stem (ES) cells in defined architectures. By inducing the morphogen WNT3A and its antagonist DKK1 from organizer cells, we generated diverse morphogen gradients, varying in range and steepness.
View Article and Find Full Text PDFJ Orthop Surg Res
December 2024
Department of Orthopedics, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, 315000, China.
Background: Tendinopathy is very common in clinical practice, which is highly prevalent in athletes, sports enthusiasts and other people involved in high-load weight-bearing activities. Common types of tendinopathy include rotator cuff injury, Achilles tendinitis, tennis elbow and so on. Macrophages (Macs) are key immune cells in the pathogenesis of tendinopathy.
View Article and Find Full Text PDFAnn Anat
December 2024
Department of Anatomy, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan. Electronic address:
Background: Erythroid cells contribute to embryonic organ development and adult tissue repair supplying oxygen to tissues. During mouse development, the primitive erythroid cells produced in the extraembryonic blood islands of the yolk sac begin to circulate as immature and nucleated erythroblasts with the onset of cardiac contractions around embryonic day 9.5 (E9.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2024
Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Weifang, China.
Systemic lupus erythematosus (SLE) is an autoimmune condition that is characterized by the production of autoantibodies and sustained inflammatory damage. Coronary heart disease (CHD) is a common complication of SLE, significantly increases CHD-related mortality in SLE patients. Despite conventional risk factors, the mechanisms contributing to a higher CHD risk require further investigation, with the immune and inflammatory aspects of SLE playing a significant role.
View Article and Find Full Text PDFCoron Artery Dis
December 2024
Department of Cardiology, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou City, Jiangsu Province, China.
Objective: Acute myocardial infarction (AMI) and the following heart failure are main causes of disability and death across the globe. Endothelial progenitor cell (EPC) levels are linked to AMI. Herein, we assessed the predictive value of EPCs for post-percutaneous coronary intervention (PCI) ventricular remodeling in AMI patients.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!