LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 125

Search options

  1. Article: Engraftment of Kidney Organoids In Vivo.

    Freedman, Benjamin S / Dekel, Benjamin

    Current transplantation reports

    2023  Volume 10, Issue 2, Page(s) 29–39

    Abstract: Purpose of review: Kidney organoids are heterocellular structures grown in vitro that resemble nephrons. Organoids contain diverse cell types, including podocytes, proximal tubules, and distal tubules in contiguous segments, patterned along a proximal- ... ...

    Abstract Purpose of review: Kidney organoids are heterocellular structures grown in vitro that resemble nephrons. Organoids contain diverse cell types, including podocytes, proximal tubules, and distal tubules in contiguous segments, patterned along a proximal-to-distal axis. Human organoids are being explored for their potential as regenerative grafts, as an alternative to allograft transplants and hemodialysis. Earlier work, analyzing grafts of developing human kidney tissue and whole human embryonic kidney rudiments, serves as a baseline for organoid implantation experiments.
    Recent findings: When transplanted into immunodeficient mice beneath the kidney capsule, kidney organoid xenografts can form vascularized, glomerulus-like structures, which exhibit a degree of filtration function. However, the absence of an appropriate collecting duct outlet and the presence of abundant stromal-like cells limits the functionality of such grafts and raises safety concerns. Recently, ureteric-like organoids have also been generated, which extend projections that resemble collecting ducts.
    Summary: Combining nephron-like and ureteric-like organoids, along with renal stromal cells, may provide a path towards more functional grafts.
    Language English
    Publishing date 2023-04-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2196-3029
    ISSN 2196-3029
    DOI 10.1007/s40472-023-00397-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article: [THE BIG CHALLENGES OF PEDIATRIC NEPHROLOGY AT THE OUTSET OF THE THIRD DECADE OF THE 21ST CENTURY].

    Pleniceanu, Oren / Dekel, Benjamin

    Harefuah

    2021  Volume 160, Issue 12, Page(s) 827–832

    Abstract: Introduction: Over the past few decades, there have been tremendous advancements in the field of nephrology due to developments in genetics and molecular biology, such as the ability to pinpoint the causative mutations in congenital syndromes involving ... ...

    Abstract Introduction: Over the past few decades, there have been tremendous advancements in the field of nephrology due to developments in genetics and molecular biology, such as the ability to pinpoint the causative mutations in congenital syndromes involving the kidneys, animal models of kidney disease and an array of tools for manipulating nucleic acids. However, despite these achievements, in most cases, these sophisticated technologies have yet to translate into improved outcomes. Thus, there are still several important challenges in the field of pediatric nephrology, the most important of which are reviewed herein. These include: 1. Better understanding of the association between a specific genotype and disease phenotype in congenital anomalies of the kidney and urinary tract, and development of effective treatments for these anomalies. 2. Deeper understanding of the pathophysiology of genetic kidney diseases. 3. Application of the available molecular tools for the purpose of genetic treatments of congenital kidney disease. 4. Uncovering the underlying mechanisms of renal fibrosis and establishment of effective means of halting/preventing it. Advancements in any of these areas have a great potential to influence the prognosis of children with kidney diseases, and considering the fast pace in which new knowledge is acquired and technologies are developed, it is expected that at least some of these challenges will be met in the foreseeable future.
    MeSH term(s) Animals ; Humans ; Kidney ; Kidney Diseases/diagnosis ; Kidney Diseases/genetics ; Kidney Diseases/therapy ; Nephrology ; Prognosis ; Urinary Tract
    Language Hebrew
    Publishing date 2021-12-27
    Publishing country Israel
    Document type Journal Article ; Review
    ZDB-ID 953872-0
    ISSN 0017-7768
    ISSN 0017-7768
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Characterization of Alternative Splicing in High-Risk Wilms' Tumors.

    Trink, Yaron / Urbach, Achia / Dekel, Benjamin / Hohenstein, Peter / Goldberger, Jacob / Kalisky, Tomer

    International journal of molecular sciences

    2024  Volume 25, Issue 8

    Abstract: The significant heterogeneity of Wilms' tumors between different patients is thought to arise from genetic and epigenetic distortions that occur during various stages of fetal kidney development in a way that is poorly understood. To address this, we ... ...

    Abstract The significant heterogeneity of Wilms' tumors between different patients is thought to arise from genetic and epigenetic distortions that occur during various stages of fetal kidney development in a way that is poorly understood. To address this, we characterized the heterogeneity of alternative mRNA splicing in Wilms' tumors using a publicly available RNAseq dataset of high-risk Wilms' tumors and normal kidney samples. Through Pareto task inference and cell deconvolution, we found that the tumors and normal kidney samples are organized according to progressive stages of kidney development within a triangle-shaped region in latent space, whose vertices, or "archetypes", resemble the cap mesenchyme, the nephrogenic stroma, and epithelial tubular structures of the fetal kidney. We identified a set of genes that are alternatively spliced between tumors located in different regions of latent space and found that many of these genes are associated with the epithelial-to-mesenchymal transition (EMT) and muscle development. Using motif enrichment analysis, we identified putative splicing regulators, some of which are associated with kidney development. Our findings provide new insights into the etiology of Wilms' tumors and suggest that specific splicing mechanisms in early stages of development may contribute to tumor development in different patients.
    MeSH term(s) Wilms Tumor/genetics ; Wilms Tumor/pathology ; Humans ; Alternative Splicing ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Kidney/metabolism ; Kidney/pathology
    Language English
    Publishing date 2024-04-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25084520
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: The Ever-Expanding Kidney Repair Shop.

    Dekel, Benjamin

    Journal of the American Society of Nephrology : JASN

    2015  Volume 27, Issue 6, Page(s) 1579–1581

    MeSH term(s) Cell Differentiation ; Kidney ; Regeneration ; Stem Cells
    Language English
    Publishing date 2015-12-07
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2015111207
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Characterization of Continuous Transcriptional Heterogeneity in High-Risk Blastemal-Type Wilms' Tumors Using Unsupervised Machine Learning.

    Trink, Yaron / Urbach, Achia / Dekel, Benjamin / Hohenstein, Peter / Goldberger, Jacob / Kalisky, Tomer

    International journal of molecular sciences

    2023  Volume 24, Issue 4

    Abstract: Wilms' tumors are pediatric malignancies that are thought to arise from faulty kidney development. They contain a wide range of poorly differentiated cell states resembling various distorted developmental stages of the fetal kidney, and as a result, ... ...

    Abstract Wilms' tumors are pediatric malignancies that are thought to arise from faulty kidney development. They contain a wide range of poorly differentiated cell states resembling various distorted developmental stages of the fetal kidney, and as a result, differ between patients in a continuous manner that is not well understood. Here, we used three computational approaches to characterize this continuous heterogeneity in high-risk blastemal-type Wilms' tumors. Using Pareto task inference, we show that the tumors form a triangle-shaped continuum in latent space that is bounded by three tumor archetypes with "stromal", "blastemal", and "epithelial" characteristics, which resemble the un-induced mesenchyme, the cap mesenchyme, and early epithelial structures of the fetal kidney. By fitting a generative probabilistic "grade of membership" model, we show that each tumor can be represented as a unique mixture of three hidden "topics" with blastemal, stromal, and epithelial characteristics. Likewise, cellular deconvolution allows us to represent each tumor in the continuum as a unique combination of fetal kidney-like cell states. These results highlight the relationship between Wilms' tumors and kidney development, and we anticipate that they will pave the way for more quantitative strategies for tumor stratification and classification.
    MeSH term(s) Child ; Humans ; Kidney Neoplasms/pathology ; Unsupervised Machine Learning ; Wilms Tumor ; Kidney/pathology
    Language English
    Publishing date 2023-02-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24043532
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Mixing Cells for Vascularized Kidney Regeneration.

    Namestnikov, Michael / Pleniceanu, Oren / Dekel, Benjamin

    Cells

    2021  Volume 10, Issue 5

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Animals ; Endothelial Cells/transplantation ; Human Embryonic Stem Cells/transplantation ; Humans ; Mesenchymal Stem Cell Transplantation ; Mice ; Mouse Embryonic Stem Cells/transplantation ; Regenerative Medicine/methods ; Renal Insufficiency, Chronic/therapy ; Specimen Handling/methods
    Language English
    Publishing date 2021-05-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10051119
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Mixing Cells for Vascularized Kidney Regeneration

    Michael Namestnikov / Oren Pleniceanu / Benjamin Dekel

    Cells, Vol 10, Iss 1119, p

    2021  Volume 1119

    Abstract: 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 ... ...

    Abstract 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.
    Keywords kidney regeneration ; vascularization ; cellular therapy ; stem-cells ; iPSCs organoids ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  8. Article ; Online: RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis.

    Pode-Shakked, Naomi / Slack, Megan / Sundaram, Nambirajan / Schreiber, Ruth / McCracken, Kyle W / Dekel, Benjamin / Helmrath, Michael / Kopan, Raphael

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 8159

    Abstract: Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) is a fatal genetic disorder characterized by complete absence or severe depletion of proximal tubules (PT) in patients harboring pathogenic variants in genes involved in the Renin-Angiotensin- ... ...

    Abstract Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) is a fatal genetic disorder characterized by complete absence or severe depletion of proximal tubules (PT) in patients harboring pathogenic variants in genes involved in the Renin-Angiotensin-Aldosterone System. To uncover the pathomechanism of AR-RTD, differentiation of ACE-/- and AGTR1-/- induced pluripotent stem cells (iPSCs) and AR-RTD patient-derived iPSCs into kidney organoids is leveraged. Comprehensive marker analyses show that both mutant and control organoids generate indistinguishable PT in vitro under normoxic (21% O2) or hypoxic (2% O2) conditions. Fully differentiated (d24) AGTR1-/- and control organoids transplanted under the kidney capsule of immunodeficient mice engraft and mature well, as do renal vesicle stage (d14) control organoids. By contrast, d14 AGTR1-/- organoids fail to engraft due to insufficient pro-angiogenic VEGF-A expression. Notably, growth under hypoxic conditions induces VEGF-A expression and rescues engraftment of AGTR1-/- organoids at d14, as does ectopic expression of VEGF-A. We propose that PT dysgenesis in AR-RTD is primarily a non-autonomous consequence of delayed angiogenesis, starving PT at a critical time in their development.
    MeSH term(s) Humans ; Animals ; Mice ; Renin-Angiotensin System/genetics ; Angiogenesis ; Vascular Endothelial Growth Factor A ; Kidney Tubules, Proximal/pathology ; Organoids
    Chemical Substances Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2023-12-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43795-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis

    Naomi Pode-Shakked / Megan Slack / Nambirajan Sundaram / Ruth Schreiber / Kyle W. McCracken / Benjamin Dekel / Michael Helmrath / Raphael Kopan

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 18

    Abstract: Abstract Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) is a fatal genetic disorder characterized by complete absence or severe depletion of proximal tubules (PT) in patients harboring pathogenic variants in genes involved in the Renin–Angiotensin– ...

    Abstract Abstract Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) is a fatal genetic disorder characterized by complete absence or severe depletion of proximal tubules (PT) in patients harboring pathogenic variants in genes involved in the Renin–Angiotensin–Aldosterone System. To uncover the pathomechanism of AR-RTD, differentiation of ACE-/- and AGTR1-/- induced pluripotent stem cells (iPSCs) and AR-RTD patient-derived iPSCs into kidney organoids is leveraged. Comprehensive marker analyses show that both mutant and control organoids generate indistinguishable PT in vitro under normoxic (21% O2) or hypoxic (2% O2) conditions. Fully differentiated (d24) AGTR1-/- and control organoids transplanted under the kidney capsule of immunodeficient mice engraft and mature well, as do renal vesicle stage (d14) control organoids. By contrast, d14 AGTR1-/- organoids fail to engraft due to insufficient pro-angiogenic VEGF-A expression. Notably, growth under hypoxic conditions induces VEGF-A expression and rescues engraftment of AGTR1-/- organoids at d14, as does ectopic expression of VEGF-A. We propose that PT dysgenesis in AR-RTD is primarily a non-autonomous consequence of delayed angiogenesis, starving PT at a critical time in their development.
    Keywords Science ; Q
    Subject code 616
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  10. Article: Regenerative medicine and stem cell therapy.

    Dekel, Benjamin

    The Israel Medical Association journal : IMAJ

    2006  Volume 8, Issue 1, Page(s) 60

    MeSH term(s) Humans ; Regeneration ; Research ; Stem Cell Transplantation/trends ; Tissue Engineering/trends
    Language English
    Publishing date 2006-01
    Publishing country Israel
    Document type Journal Article
    ZDB-ID 2008291-5
    ISSN 1565-1088 ; 0021-2180
    ISSN 1565-1088 ; 0021-2180
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top