Interactions of the Immune System with Human Kidney Organoids.

Kidney organoids are an innovative tool in transplantation research. The aim of the present study was to investigate whether kidney organoids are susceptible for allo-immune attack and whether they can be used as a model to study allo-immunity in kidney transplantation. Human induced pluripotent stem cell-derived kidney organoids were co-cultured with human peripheral blood mononuclear cells (PBMC), which resulted in invasion of allogeneic T-cells around nephron structures and macrophages in the stromal cell compartment of the organoids. This process was associated with the induction of fibrosis. Subcutaneous implantation of kidney organoids in immune-deficient mice followed by adoptive transfer of human PBMC led to the invasion of diverse T-cell subsets. Single cell transcriptomic analysis revealed that stromal cells in the organoids upregulated expression of immune response genes upon immune cell invasion. Moreover, immune regulatory PD-L1 protein was elevated in epithelial cells while genes related to nephron differentiation and function were downregulated. This study characterized the interaction between immune cells and kidney organoids, which will advance the use of kidney organoids for transplantation research.

Corrigendum: The mast cell: A Janus in kidney transplants.

[This corrects the article DOI: 10.3389/fimmu.2023.1122409.].

The mast cell: A Janus in kidney transplants.

Mast cells (MCs) are innate immune cells with a versatile set of functionalities, enabling them to orchestrate immune responses in various ways. Aside from their known role in allergy, they also partake in both allograft tolerance and rejection through interaction with regulatory T cells, effector T cells, B cells and degranulation of cytokines and other mediators. MC mediators have both pro- and anti-inflammatory actions, but overall lean towards pro-fibrotic pathways. Paradoxically, they are also seen as having potential protective effects in tissue remodeling post-injury. This manuscript elaborates on current knowledge of the functional diversity of mast cells in kidney transplants, combining theory and practice into a MC model stipulating both protective and harmful capabilities in the kidney transplant setting.

Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing.

The kidney is among the most complex organs in terms of the variety of cell types. The cellular complexity of human kidneys is not fully unraveled and this challenge is further complicated by the existence of multiple progenitor pools and differentiation pathways. Researchers disagree on the variety of renal cell types due to a lack of research providing a comprehensive picture and the challenge to translate findings between species. To find an answer to the number of human renal cell types, we discuss research that used single-cell RNA sequencing on developing and adult human kidney tissue and compares these findings to the literature of the pre-single-cell RNA sequencing era. We find that these publications show major steps towards the discovery of novel cell types and intermediate cell stages as well as complex molecular signatures and lineage pathways throughout development. The variety of cell types remains variable in the single-cell literature, which is due to the limitations of the technique. Nevertheless, our analysis approaches an accumulated number of 41 identified cell populations of renal lineage and 32 of non-renal lineage in the adult kidney, and there is certainly much more to discover. There is still a need for a consensus on a variety of definitions and standards in single-cell RNA sequencing research, such as the definition of what is a cell type. Nevertheless, this early-stage research already proves to be of significant impact for both clinical and regenerative medicine, and shows potential to enhance the generation of sophisticated in vitro kidney tissue.

Analysis of myocardial deformation based on pixel tracking in two dimensional echocardiographic images enables quantitative assessment of regional left ventricular function.

OBJECTIVE: To evaluate whether myocardial strain and strain rate calculated from two dimensional echocardiography by automatic frame-by-frame tracking of natural acoustic markers enables objective description of regional left ventricular (LV) function. METHODS: In 64 patients parasternal two dimensional echocardiographic views at the apical, mid-ventricular and basal levels were obtained. An automatic frame-by-frame tracking system of natural acoustic echocardiographic markers was used to calculate radial strain, circumferential strain, radial strain rate and circumferential strain rate for each LV segment in a 16 segment model. Cardiac magnetic resonance imaging (cMRI) was performed to define segmental LV function as normokinetic, hypokinetic or akinetic. RESULTS: Image quality was sufficient for adequate strain and strain-rate analysis from two dimensional echocardiographic images obtained from parasternal views in 88% of segments. Obtained radial strain data were highly reproducible and analysis was affected by only small intraobserver (mean 4.4 (SD 1.6)%) and interobserver variabilities (7.3 (2.5)%). Each of the analysed strain and strain-rate parameters was significantly different between segments defined as normokinetic, hypokinetic or akinetic by cMRI (radial strain 36.8 (10.5)%, 24.1 (7.5)% and 13.4 (4.8)%, respectively, p < 0.001). Peak systolic radial strain enabled detection of hypokinesis or akinesis with a sensitivity of 83.5% and a specificity of 83.5% (cut off value 29.1%, receiver operating characteristic (ROC) curve area 0.905, 95% CI 0.883 to 0.923). Peak systolic radial strain analysis also enabled detection of akinesis versus hypokinesis with a sensitivity of 82.7% and a specificity of 94.5% (cut off value 21.0%, ROC curve area 0.946). Peak systolic radial strain-rate analysis was less accurate than peak systolic radial strain analysis to detect cMRI-defined segmental function abnormalities. The accuracy of peak systolic circumferential strain and strain rate was similar to that of corresponding radial parameters. CONCLUSIONS: Frame-by-frame tracking of acoustic markers in two dimensional echocardiographic images enables accurate analysis of regional systolic LV function.