Biology subjects

Lindstedt, S.

Publications and source records attributed to Lindstedt, S..

3 recordsLinked to original sources

bioRxiv2026

Cell therapy for regeneration of injured donor lungs for transplantation

Donor organ shortage remains the major barrier to transplantation resulting in deaths on the waiting list. For lungs, aspiration-related injury is a common cause of donor organ discard and increases the risk of primary graft dysfunction. Currently, no effective therapies exist to repair damaged donor lungs prior to transplantation. Here, we investigated whether mesenchymal stromal cells (MSCs) from bone marrow or full-term amniotic fluid could restore severely injured donor lungs in a porcine model integrating ex vivo lung perfusion, transplantation and post-transplant follow-up (n=48; 24 donors, 24 recipients). MSCs were administered either once during ex vivo lung perfusion or repeatedly across lung perfusion and the early post-transplant period and compared with placebo treated controls. A single dose conferred only partial benefit, whereas repeated dosing restored graft function, normalized gas exchange and haemodynamics, and prevented graft dysfunction. MSCs from both sources were similarly effective in repeated regimens. These findings identify dosing schedule, rather than cell source, as key determinant of durable organ rescue and support perfusion-guided cell therapy as potentially generalizable regenerative strategy across solid-organ transplantation.

cell biology↗

bioRxiv2020

Isolation of high yield and quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts

Precision-cut lung slices (PCLS) have gained increasing interest as a model to study lung biology and disease, as well as for screening novel therapeutics. In particular, PCLS derived from human tissue can better recapitulate some aspects of lung biology and disease as compared to PCLS derived from animals (e.g. clinical heterogeneity), but access to human tissue is limited. A number of different experimental readouts have been established for use with PCLS, but obtaining high yield and quality RNA for downstream gene expression analysis has remained challenging. This is particularly problematic for utilizing the power of next-generation sequencing techniques, such as RNA-sequencing (RNA-seq), for non-biased and high through-put analysis of PCLS human cohorts. In the current study, we present a novel approach for isolating high quality RNA from a small amount of tissue, including diseased human tissue, such as idiopathic pulmonary fibrosis (IPF). We show that the RNA isolated using this method is of sufficient quality for both RT-qPCR and RNA-seq analysis. Furthermore, the RNA-seq data from human PCLS was comparable to data generated from native tissue and could be used in several established computational pipelines, including deconvolution of bulk RNA-seq data using publicly available single-cell RNA-seq data sets. Deconvolution using Bisque revealed a diversity of cell populations in human PCLS derived from distal lung tissue, including several immune cell populations, which correlated with cell populations known to be present and aberrant in human disease, such as IPF.

molecular biology↗

bioRxiv2020

Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

Nanomedicines hold immense promise for a number of devastating diseases due to the ability to custom-design both the carrier and cargo. However, their clinical implementation has been hampered by physicochemical and biological barriers and off-target deposition which impair cell specific targeting, especially in internal organs. This study reports a new delivery approach using organ-restricted vascular delivery to allow for direct administration and recirculation of stimuli-responsive nanoparticles to promote cellular uptake into an organ of interest. Using this technique, nanoparticles reach the interior of dense tumors and are selectively taken up by lung cancer cells. Importantly, this surgical approach is essential as the same nanoparticles do not reach lung tumor cells upon systemic or intratracheal administration. Organ-restricted vascular delivery thus opens up new avenues for optimized nanotherapies for cancer and other diseases.

pharmacology and toxicology↗