Objective: The purpose of the study was to determine whether hematopoietic stem cell (HSCs) mobilization can regulate early diabetic retinopathy in mice.
Methods: Mice were divided into four groups: control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC-mobilized group. Murine stem cell growth factor (SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. The changes associated with autologous HSCs mobilization were characterized using flow cytometry, Immunohistochemistry and semiquantitative RT-PCR. Evans blue quantitative test was used to measure the breakdown level of blood-retina barrier.
Results: HSCs were marked by CD34-/low and Sca1+ in this study. The acceleration of endothelial cell regeneration was observed. A decrease of VEGF expression due to autologous stem cell mobilization was found. HSCs could increase the content of VEGFR-2 in mouse retina and significantly downregulated the expression of VEGF and ang-2 in diabetic mice.
Conclusions: The experiment suggest that autologous HSCs mobilization can be approach of therapeutic vascular reconstruction and functional restoration of blood-retina barrier in mice.
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Front Immunol
January 2025
Department of Ophthalmology, National University Hospital, National University Health System, Singapore, Singapore.
Autoimmune retinopathy (AIR) is a rare, potentially blinding retinal disease that remains a challenging condition to manage when resistant to conventional immune-modulatory approaches. We report clinical and electrophysiological improvement in a 49-year-old patient who underwent an autologous hematopoietic stem cell transplant (aHSCT) for thymoma-associated AIR after experiencing progressive disease despite receiving periocular and systemic steroids, mycophenolate mofetil, baricitinib, tacrolimus, bortezomib, rituximab, plasmapheresis, and intravenous immunoglobulin. The aHSCT had two stages: (i) peripheral blood stem cell harvest following mobilization with cyclophosphamide and granulocyte colony-stimulating factor, and (ii) conditioning regimen with plasmapheresis, rituximab, cyclophosphamide, and anti-thymocyte globulin high-dose therapy, followed by autologous hematopoietic cell infusion of 5.
View Article and Find Full Text PDFTransfus Apher Sci
January 2025
Pediatric Cell and Gene Therapy Research Centre, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Background: Neuroblastoma (NB) is the most common extracranial solid tumor in pediatric. In highrisk NB patients, the 5-year overall survival rate (OS) remains a stark < 50 % with conventional therapies. Autologous hematopoietic stem cell transplantation with high dose chemotherapies was used in poor prognosis and high-risk patients.
View Article and Find Full Text PDFStem Cells Dev
January 2025
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Autologous hematopoietic stem cell transplantation is used to restore bone marrow function after high-dose chemotherapy. For apheresis, granulocyte colony-stimulating factor (G-CSF) is standard of care, but obtaining sufficient stem cells can be challenging. Other mobilization agents include plerixafor and PEGylated G-CSF (PEG-G-CSF).
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Background: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of α-galactosidase A (α-gal A) activity. Our goal was to correct the enzyme deficiency in Fabry patients by transferring the cDNA for α-gal A into their CD34+ hematopoietic stem/progenitor cells (HSPCs). Overexpression of α-gal A leads to secretion of the hydrolase; which can be taken up and used by uncorrected bystander cells.
View Article and Find Full Text PDFNat Commun
January 2025
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
The only cure of HIV has been achieved in a small number of people who received a hematopoietic stem cell transplant (HSCT) comprising allogeneic cells carrying a rare, naturally occurring, homozygous deletion in the CCR5 gene. The rarity of the mutation and the significant morbidity and mortality of such allogeneic transplants precludes widespread adoption of this HIV cure. Here, we show the application of CRISPR/Cas9 to achieve >90% CCR5 editing in human, mobilized hematopoietic stem progenitor cells (HSPC), resulting in a transplant that undergoes normal hematopoiesis, produces CCR5 null T cells, and renders xenograft mice refractory to HIV infection.
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