scholarly journals Mixing Cells for Vascularized Kidney Regeneration

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1119
Author(s):  
Michael Namestnikov ◽  
Oren Pleniceanu ◽  
Benjamin Dekel
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cellular Therapy ◽  
Kidney Tissue ◽  
Kidney Regeneration ◽  
Cell Sources ◽  
Therapy Strategies ◽  
Different Sources ◽  
Made In

The worldwide rise in prevalence of chronic kidney disease (CKD) demands innovative bio-medical solutions for millions of kidney patients. Kidney regenerative medicine aims to replenish tissue which is lost due to a common pathological pathway of fibrosis/inflammation and rejuvenate remaining tissue to maintain sufficient kidney function. To this end, cellular therapy strategies devised so far utilize kidney tissue-forming cells (KTFCs) from various cell sources, fetal, adult, and pluripotent stem-cells (PSCs). However, to increase engraftment and potency of the transplanted cells in a harsh hypoxic diseased environment, it is of importance to co-transplant KTFCs with vessel forming cells (VFCs). VFCs, consisting of endothelial cells (ECs) and mesenchymal stem-cells (MSCs), synergize to generate stable blood vessels, facilitating the vascularization of self-organizing KTFCs into renovascular units. In this paper, we review the different sources of KTFCs and VFCs which can be mixed, and report recent advances made in the field of kidney regeneration with emphasis on generation of vascularized kidney tissue by cell transplantation.

Generating Kidney from Stem Cells

2019 ◽  
Vol 81 (1) ◽  
pp. 335-357 ◽  
Author(s):  
Melissa H. Little ◽  
Lorna J. Hale ◽  
Sara E. Howden ◽  
Santhosh V. Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cellular Therapy ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Human Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Cellular Therapies

Human kidney tissue can now be generated via the directed differentiation of human pluripotent stem cells. This advance is anticipated to facilitate the modeling of human kidney diseases, provide platforms for nephrotoxicity screening, enable cellular therapy, and potentially generate tissue for renal replacement. All such applications will rely upon the accuracy and reliability of the model and the capacity for stem cell–derived kidney tissue to recapitulate both normal and diseased states. In this review, we discuss the models available, how well they recapitulate the human kidney, and how far we are from application of these cells for use in cellular therapies.

scholarly journals Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 750
Author(s):  
Pasquale Marrazzo ◽  
Valeria Pizzuti ◽  
Silvia Zia ◽  
Azzurra Sargenti ◽  
Daniele Gazzola ◽  
...  
Keyword(s):  
Stem Cells ◽  
Defense Mechanisms ◽  
Live Cells ◽  
Label Free ◽  
Bacterial Diseases ◽  
Prospective Application ◽  
Therapy Strategies ◽  
Stromal Stem Cells ◽  
Different Sources

Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.

scholarly journals Episomal Induced Pluripotent Stem Cells: Functional and Potential Therapeutic Applications

2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 112S-131S
Author(s):  
Aline Yen Ling Wang ◽  
Charles Yuen Yung Loh
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Safety Profile ◽  
Current Trend ◽  
Functional Restoration ◽  
Clinical Scenarios ◽  
Cell Sources ◽  
Induced Pluripotent ◽  
A Current

The term episomal induced pluripotent stem cells (EiPSCs) refers to somatic cells that are reprogrammed into induced pluripotent stem cells (iPSCs) using non-integrative episomal vector methods. This reprogramming process has a better safety profile compared with integrative methods using viruses. There is a current trend toward using episomal plasmid reprogramming to generate iPSCs because of the improved safety profile. Clinical reports of potential human cell sources that have been successfully reprogrammed into EiPSCs are increasing, but no review or summary has been published. The functional applications of EiPSCs and their potential uses in various conditions have been described, and these may be applicable to clinical scenarios. This review summarizes the current direction of EiPSC research and the properties of these cells with the aim of explaining their potential role in clinical applications and functional restoration.

scholarly journals Cell Replacement Therapy for Retinal and Optic Nerve Diseases: Cell Sources, Clinical Trials and Challenges

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 865
Author(s):  
Rosa M. Coco-Martin ◽  
Salvador Pastor-Idoate ◽  
Jose Carlos Pastor
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Optic Nerve ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Limbal Stem Cells ◽  
Term Survival ◽  
Cell Therapies ◽  
Optic Nerve Diseases ◽  
Cell Sources

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce a localized retinal detachment to perform the subretinal placement of the transplanted cell; (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

scholarly journals MYCL promotes iPSC-like colony formation via MYC Box 0 and 2 domains

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chiaki Akifuji ◽  
Mio Iwasaki ◽  
Yuka Kawahara ◽  
Chiho Sakurai ◽  
Yu-Shen Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Pluripotent Stem Cells ◽  
Cytoskeletal Proteins ◽  
Germline Transmission ◽  
Phenotypic Differences ◽  
Reprogramming Efficiency ◽  
Cell Sources ◽  
Low Efficiency ◽  
Induced Pluripotent

AbstractHuman induced pluripotent stem cells (hiPSCs) can differentiate into cells of the three germ layers and are promising cell sources for regenerative medicine therapies. However, current protocols generate hiPSCs with low efficiency, and the generated iPSCs have variable differentiation capacity among different clones. Our previous study reported that MYC proteins (c-MYC and MYCL) are essential for reprogramming and germline transmission but that MYCL can generate hiPSC colonies more efficiently than c-MYC. The molecular underpinnings for the different reprogramming efficiencies between c-MYC and MYCL, however, are unknown. In this study, we found that MYC Box 0 (MB0) and MB2, two functional domains conserved in the MYC protein family, contribute to the phenotypic differences and promote hiPSC generation in MYCL-induced reprogramming. Proteome analyses suggested that in MYCL-induced reprogramming, cell adhesion-related cytoskeletal proteins are regulated by the MB0 domain, while the MB2 domain regulates RNA processes. These findings provide a molecular explanation for why MYCL has higher reprogramming efficiency than c-MYC.

scholarly journals Therapeutic Potential of Human Induced Pluripotent Stem Cells and Renal Progenitor Cells in Experimental Chronic Kidney Disease

2020 ◽  
Author(s):  
Patrícia de Carvalho Ribeiro ◽  
Fernando Henrique Lojudice ◽  
Ida Maria Maximina Fernandes-Charpiot ◽  
Maria Alice Sperto Ferreira Baptista ◽  
Stanley de Almeida Araújo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Kidney Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Positive Staining ◽  
Post Surgery ◽  
Induced Pluripotent ◽  
Renal Progenitor

Abstract BackgroundChronic Kidney Disease (CKD) is a global public health problem. Regenerative medicine using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.MethodsWe transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitors cells (RPCs) into a CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology and immunohistochemistry were evaluated 45 days post-surgery. ResultsWe successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.ConclusionsIn conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seems to be more efficient than RPCs, possibly due to an anti-inflammatory mechanism triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improve clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.

scholarly journals A simple bioreactor-based method to generate kidney organoids from pluripotent stem cells

2017 ◽  
Author(s):  
Aneta Przepiorski ◽  
Veronika Sander ◽  
Tracy Tran ◽  
Jennifer A. Hollywood ◽  
Brie Sorrenson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Kidney Development ◽  
Kidney Tissue ◽  
Experimental System ◽  
Human Kidney ◽  
Cost Effective ◽  
Cost Effective Method ◽  
Induced Pluripotent ◽  
Kidney Organoids

SummaryKidney organoids generated from human pluripotent stem cells have the potential to revolutionize how kidney development and injury are studied. Current protocols are technically complex and suffer from poor reproducibility and high reagent costs restricting scalability. To overcome these issues, we have established a simple, inexpensive and robust method to grow kidney organoids in bulk from human induced pluripotent stem cells. Our organoids develop tubular structures by day (d) 8 and show optimal tissue morphology at d14. A comparison with fetal human kidney suggests that d14 organoid renal structures most closely resemble ‘capillary loop’ stage nephrons. We show that deletion of HNF1B, a transcription factor linked to congenital kidney defects, interferes with tubulogenesis, validating our experimental system for studying renal developmental biology. Taken together, our protocol provides a fast, efficient and cost-effective method for generating large quantities of human fetal kidney tissue, enabling the study of normal and aberrant human renal development.

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