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In the field of cell therapy for heart disease, a new paradigm of repeated dosing of cells has recently emerged. However, the lack of a repeatable cell delivery method in preclinical studies in rodents is a major obstacle to investigating this paradigm. We have established and standardized a method of echocardiography-guided percutaneous left ventricular intracavitary injection (echo-guided LV injection) as a cell delivery approach in infarcted mice. Here, we describe the method in detail and address several important issues regarding it. First, by integrating anatomical and echocardiographic considerations, we have established strategies to determine a safe anatomical window for injection in infarcted mice. Second, we summarize our experience with this method (734 injections). The overall survival rate was 91.4%. Third, we examined the efficacy of this cell delivery approach. Compared with vehicle treatment, cardiac mesenchymal cells (CMCs) delivered via this method improved cardiac function assessed both echocardiographically and hemodynamically. Furthermore, repeated injections of CMCs via this method yielded greater cardiac function improvement than single-dose administration. Echo-guided LV injection is a feasible, reproducible, relatively less invasive and effective delivery method for cell therapy in murine models of heart disease. It is an important approach that could move the field of cell therapy forward, especially with regard to repeated cell administrations.
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http://dx.doi.org/10.1007/s11010-021-04077-6 | DOI Listing |
Crit Rev Ther Drug Carrier Syst
January 2025
Department of Pharmacology, PSG College of Pharmacy, Coimbatore 641004, Tamil Nadu, India.
Treating neurological disorders is challenging due to the blood-brain barrier (BBB), which limits therapeutic agents, including proteins and peptides, from entering the central nervous system. Despite their potential, the BBB's selective permeability is a significant obstacle. This review explores recent advancements in protein therapeutics for BBB-targeted delivery and highlights computational tools.
View Article and Find Full Text PDFBlood Adv
September 2025
Institut de Recherches Cliniques de Montreal - IRCM, Montreal, Quebec, Canada.
Acute myeloid leukemia (AML) with rearrangement of the mixed lineage leukemia gene express MLL-AF9 fusion protein, a transcription factor that impairs differentiation and drives expansion of leukemic cells. We report here that the zinc finger protein GFI1 together with the histone methyltransferase LSD1 occupies the promoter and regulates expression of the lncRNA ELDR in the MLL-r AML cell line THP-1. Forced ELDR overexpression enhanced the growth inhibition of an LSD1i/ATRA combination treatment and reduced the capacity of these cells to generate leukemia in xenografts, leading to a longer leukemia-free survival.
View Article and Find Full Text PDFCornea
September 2025
Department of Ophthalmology, University of California Los Angeles, Los Angeles, CA.
Purpose: To evaluate visual outcomes after bacterial keratitis (BK) and identify predictive factors for poor prognosis at a tertiary referral center in Southern California.
Methods: This is a cross-sectional retrospective review of patients' medical records with culture-positive BK at University of California Los Angeles from January 1, 2014, to December 31, 2019. Main outcome measure was change in best-corrected visual acuity (BCVA) at 12 weeks posttreatment.
Am J Physiol Lung Cell Mol Physiol
September 2025
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Cystic Fibrosis (CF) is a multiorgan disease caused by mutations in the gene, leading to chronic pulmonary infections and hyperinflammation. Among pathogens colonizing the CF lung, is predominant, infecting over 50% of adults with CF, and becoming antibiotic-resistant over time. Current therapies for CF, while providing tremendous benefits, fail to eliminate persistent bacterial infections, chronic inflammation, and irreversible lung damage, necessitating novel therapeutic strategies.
View Article and Find Full Text PDFElectroporation is a promising technology utilizing electrical pulses for macromolecule delivery and soft-tissue ablation, with applications that include next-generation prophylactics and the treatment of genetic diseases such as cancer. This study demonstrates a high-throughput capable 3D tissue culture model for quantification of the reversible and irreversible electroporation thresholds for a given electroporation protocol. By using a non-uniform electric field and analyzing the spatial distribution of transfected cells, both reversible and irreversible thresholds can be identified within a single sample, increasing the efficiency at which electroporation protocols can be characterized, especially for in vivo translation.
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