Renal Interstitial Cells Promote Nephron Regeneration by Secreting Prostaglandin E2

In organ regeneration, progrnitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation and differentiation. However, what kind of cells provide a native microenvironment for renal progenitor cells has not been clarified. Here, single-cell sequencing of zebrafish kidney revealed that fabp10 was a marker of renal interstitial cells (RICs), and the Tg(fabp10a:GFP) transgenic line can specifically label RICs in zebrafish kidney. The formation of RICs and nephrons are closely accompanied during nephron regeneration. RICs form a network to wrap the renal progenitor cell aggregates. RICs in close contact with cell aggregates express cyclooxygenase 2 and secrete prostaglandin 2 (PGE2). Inhibiting PGE2 production prevented nephrogenesis by reducing the proliferation and differentiation of progenitor cell aggregates. PGE2 promoted maturation of the nephron by activating the WNT signaling pathway in progenitor cell aggregates in cooperation with Wnt4a. These findings suggest that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.

Download Full-text

Constructing an Isogenic 3D Human Nephrogenic Progenitor Cell Model Composed of Endothelial, Mesenchymal, and SIX2-Positive Renal Progenitor Cells

Stem Cells International ◽

10.1155/2019/3298432 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Lisa Nguyen ◽

Lucas-Sebastian Spitzhorn ◽

James Adjaye

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Mesenchymal Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Progenitor Cell ◽

Cell Model ◽

Renal Progenitor Cells ◽

Renal Stem Cells ◽

Renal Progenitor

Urine has become the source of choice for noninvasive renal epithelial cells and renal stem cells which can be used for generating induced pluripotent stem cells. The aim of this study was to generate a 3D nephrogenic progenitor cell model composed of three distinct cell types—urine-derived SIX2-positive renal progenitor cells, iPSC-derived mesenchymal stem cells, and iPSC-derived endothelial cells originating from the same individual. Characterization of the generated mesenchymal stem cells revealed plastic adherent growth and a trilineage differentiation potential to adipocytes, chondrocytes, and osteoblasts. Furthermore, these cells express the typical MSC markers CD73, CD90, and CD105. The induced endothelial cells express the endothelial cell surface marker CD31. Upon combination of urine-derived renal progenitor cells, induced mesenchymal stem cells, and induced endothelial cells at a set ratio, the cells self-condensed into three-dimensional nephrogenic progenitor cells which we refer to as 3D-NPCs. Immunofluorescence-based stainings of sectioned 3D-NPCs revealed cells expressing the renal progenitor cell markers (SIX2 and PAX8), podocyte markers (Nephrin and Podocin), the endothelial marker (CD31), and mesenchymal markers (Vimentin and PDGFR-β). These 3D-NPCs share kidney progenitor characteristics and thus the potential to differentiate into podocytes and proximal and distal tubules. As urine-derived renal progenitor cells can be easily obtained from cells shed into urine, the generation of 3D-NPCs directly from renal progenitor cells instead of pluripotent stem cells or kidney biopsies holds a great potential for the use in nephrotoxicity tests, drug screening, modelling nephrogenesis and diseases.

Download Full-text

Kidney Regeneration in Later-Stage Mouse Embryos via Transplanted Renal Progenitor Cells

Journal of the American Society of Nephrology ◽

10.1681/asn.2019020148 ◽

2019 ◽

Vol 30 (12) ◽

pp. 2293-2305 ◽

Cited By ~ 3

Author(s):

Shuichiro Yamanaka ◽

Yatsumu Saito ◽

Toshinari Fujimoto ◽

Tsuyoshi Takamura ◽

Susumu Tajiri ◽

...

Keyword(s):

Progenitor Cells ◽

Cell Transplantation ◽

Progenitor Cell ◽

Kidney Development ◽

Fluorescent Protein ◽

Mouse Embryos ◽

Kidney Regeneration ◽

Renal Progenitor Cells ◽

Renal Progenitor

BackgroundThe limited availability of donor kidneys for transplantation has spurred interest in investigating alternative strategies, such as regenerating organs from stem cells transplanted into animal embryos. However, there is no known method for transplanting cells into later-stage embryos, which may be the most suitable host stages for organogenesis, particularly into regions useful for kidney regeneration.MethodsWe demonstrated accurate transplantation of renal progenitor cells expressing green fluorescent protein to the fetal kidney development area by incising the opaque uterine muscle layer but not the transparent amniotic membrane. We allowed renal progenitor cell–transplanted fetuses to develop for 6 days postoperatively before removal for analysis. We also transplanted renal progenitor cells into conditional kidney-deficient mouse embryos. We determined growth and differentiation of transplanted cells in all cases.ResultsRenal progenitor cell transplantation into the retroperitoneal cavity of fetuses at E13–E14 produced transplant-derived, vascularized glomeruli with filtration function and did not affect fetal growth or survival. Cells transplanted to the nephrogenic zone produced a chimera in the cap mesenchyme of donor and host nephron progenitor cells. Renal progenitor cells transplanted to conditional kidney-deficient fetuses induced the formation of a new nephron in the fetus that is connected to the host ureteric bud.ConclusionsWe developed a cell transplantation method for midstage to late-stage fetuses. In vivo kidney regeneration from renal progenitor cells using the renal developmental environment of the fetus shows promise. Our findings suggest that fetal transplantation methods may contribute to organ regeneration and developmental research.

Download Full-text

Essential but differential role for CXCR4 and CXCR7 in the therapeutic homingof human renal progenitor cells

Journal of Experimental Medicine ◽

10.1084/jem.20071903 ◽

2008 ◽

Vol 205 (2) ◽

pp. 479-490 ◽

Cited By ~ 204

Author(s):

Benedetta Mazzinghi ◽

Elisa Ronconi ◽

Elena Lazzeri ◽

Costanza Sagrinati ◽

Lara Ballerini ◽

...

Keyword(s):

Renal Failure ◽

Progenitor Cells ◽

Chemokine Receptors ◽

Renal Fibrosis ◽

Progenitor Cell ◽

Renal Tissue ◽

Scid Mice ◽

Beneficial Effects ◽

Renal Progenitor Cells ◽

Renal Progenitor

Recently, we have identified a population of renal progenitor cells in human kidneys showing regenerative potential for injured renal tissue of SCID mice. We demonstrate here that among all known chemokine receptors, human renal progenitor cells exhibit high expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7. In SCID mice with acute renal failure (ARF), SDF-1 was strongly up-regulated in resident cells surrounding necrotic areas. In the same mice, intravenously injected renal stem/progenitor cells engrafted into injured renal tissue decreased the severity of ARF and prevented renal fibrosis. These beneficial effects were abolished by blocking either CXCR4 or CXCR7, which dramatically reduced the number of engrafting renal progenitor cells. However, although SDF-1–induced migration of renal progenitor cells was only abolished by an anti-CXCR4 antibody, transendothelial migration required the activity of both CXCR4 and CXCR7, with CXCR7 being essential for renal progenitor cell adhesion to endothelial cells. Moreover, CXCR7 but not CXCR4 was responsible for the SDF-1–induced renal progenitor cell survival. Collectively, these findings suggest that CXCR4 and CXCR7 play an essential, but differential, role in the therapeutic homing of human renal progenitor cells in ARF, with important implications for the development of stem cell–based therapies.

Download Full-text

SiO2 Promoted CaO Diffusion to C Phase at 1500 and 1700 °C

Energies ◽

10.3390/en14030587 ◽

2021 ◽

Vol 14 (3) ◽

pp. 587

Author(s):

Lijuan Ni ◽

Renxing Wang ◽

Qingya Liu ◽

Junfei Wu ◽

Yue Pan ◽

...

Keyword(s):

Mass Transfer ◽

Close Contact ◽

Chemical Changes ◽

Physical And Chemical ◽

Diffusion Behaviors

To better understand the mass transfer behaviors in CaC2 production from CaO and coke, this paper studies the diffusion behaviors of CaO and graphite, with or without ash, at 1500 and 1700 °C. CaO and graphite are pressed into tablets and heated alone or in close contact. Physical and chemical changes in these tablets are analyzed by XRD and SEM+EDX. In some experiments, thin Mo wires are placed between the closely contacted CaO and graphite tablets to identify the diffusion direction. It is found that the diffusion between CaO and low-ash graphite is very limited. SiO2 in a high-ash graphite diffuses into CaO tablet and reacts with CaO to form Ca2SiO4, which then diffuses into the graphite tablet easily and leads to CaC2 formation at 1700 °C.

Download Full-text

Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth

Basic Research in Cardiology ◽

10.1007/s00395-014-0455-4 ◽

2014 ◽

Vol 110 (1) ◽

Cited By ~ 19

Author(s):

Christelle Bielmann ◽

Stéphanie Rignault-Clerc ◽

Lucas Liaudet ◽

Feng Li ◽

Tetsuo Kunieda ◽

...

Keyword(s):

Cell Proliferation ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Progenitor Cell ◽

Cardiac Progenitor Cell ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Progenitor Cell Proliferation

Download Full-text

Kidney bioengineering by using decellularized kidney scaffold and renal progenitor cells

Tissue and Cell ◽

10.1016/j.tice.2021.101699 ◽

2021 ◽

pp. 101699

Author(s):

Chih-Yang Hsu ◽

Pei-Ling Chi ◽

Hsin-Yu Chen ◽

Shih-Hsiang Ou ◽

Kang-Ju Chou ◽

...

Keyword(s):

Progenitor Cells ◽

Renal Progenitor Cells ◽

Renal Progenitor

Download Full-text

Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain

Developmental Biology ◽

10.1016/s0012-1606(03)00120-9 ◽

2003 ◽

Vol 258 (2) ◽

pp. 319-333 ◽

Cited By ~ 209

Author(s):

Aiwu Cheng ◽

Shuqin Wang ◽

Jingli Cai ◽

Mahendra S Rao ◽

Mark P Mattson

Keyword(s):

Nitric Oxide ◽

Cell Proliferation ◽

Progenitor Cell ◽

Feedback Loop ◽

Neural Progenitor Cell ◽

Mammalian Brain ◽

Positive Feedback Loop ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Progenitor Cell Proliferation

Download Full-text

HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells

The Journal of Cell Biology ◽

10.1083/jcb.200605113 ◽

2006 ◽

Vol 174 (7) ◽

pp. 1059-1069 ◽

Cited By ~ 175

Author(s):

Lingfang Zeng ◽

Qingzhong Xiao ◽

Andriana Margariti ◽

Zhongyi Zhang ◽

Anna Zampetaki ◽

...

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Stem Cell ◽

Cell Differentiation ◽

Laminar Flow ◽

Progenitor Cell ◽

Stem Cell Differentiation ◽

Es Cell ◽

Local Flow ◽

Proliferation And Differentiation

Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress and local flow pattern. This study aims to elucidate the role of laminar flow on embryonic stem (ES) cell differentiation and the underlying mechanism. We demonstrated that laminar flow enhanced ES cell–derived progenitor cell proliferation and differentiation into endothelial cells (ECs). Laminar flow stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1–PI3K–Akt pathway, which in turn deacetylated p53, leading to p21 activation. A similar signal pathway was detected in vascular endothelial growth factor–induced EC differentiation. HDAC3 and p21 were detected in blood vessels during embryogenesis. Local transfer of ES cell–derived EPC incorporated into injured femoral artery and reduced neointima formation in a mouse model. These data suggest that shear stress is a key regulator for stem cell differentiation into EC, especially in EPC differentiation, which can be used for vascular repair, and that the Flk-1–PI3K–Akt–HDAC3–p53–p21 pathway is crucial in such a process.

Download Full-text