Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Maturation of Nephrons by Implanting hPSC-derived Kidney Progenitors Under Kidney Capsules of Unilaterally Nephrectomized Mice

Author(s): Xin Yu, Shan Jiang, Kailin Li, Xianzhen Yang, Denglu Zhang, Xiaohang Du, Kong Feng and Shengtian Zhao*

Volume 18, Issue 4, 2023

Published on: 22 September, 2022

Page: [551 - 559] Pages: 9

DOI: 10.2174/1574888X17666220818101503

Price: $65

Abstract

Background: Human pluripotent stem cell (hPSC)-derived kidney organoids may contribute to disease modeling and the generation of kidney replacement tissues. However, the realization of such applications requires the induction of hPSCs into functional mature organoids. One of the key questions for this process is whether a specific vascular system exists for nephrogenesis. Our previous study showed that short-term (2 weeks) implantation of hPSC-derived organoids below the kidney capsules of unilaterally nephrectomized and immunodeficient mice resulted in the enlargement of organoids and production of vascular cells, although signs of maturation were lacking.

Methods: Organoids were induced for 15 days in vitro and then grafted below kidney capsules of the same unilaterally nephrectomized immunodeficient mouse model to examine whether medium-term (4 weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence and transmission electron microscopy.

Results: We demonstrated that after 2–4 weeks of implantation, renal organoids formed host-derived vascularization and matured without any exogenous vascular endothelial growth factor. Glomerular filtration barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular endothelial cell development, and apical, basal podocyte polarization. A polarized monolayer epithelium and extensive brush border were also observed for tubular epithelial cells.

Conclusions: Our results indicate that the in vivo microenvironment is important for the maturation of human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following longer-term (12 weeks) implantation, suggesting effects on off-target cells during the induction process. Accordingly, induction efficiency and transplantation models should be improved in the future.

Keywords: Kidney, organoids, induced pluripotent stem cells, implantation, stromal expansion, polarization.

« Previous Next »
Graphical Abstract

[1]
Bantounas I, Ranjzad P, Tengku F. Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors. Stem Cell Reports 2018; 10(3): 766-79.
[2]
Liyanage T, Ninomiya T, Jha V, et al. Worldwide access to treatment for end-stage kidney disease: A systematic review. Lancet 2015; 385(9981): 1975-82.
[http://dx.doi.org/10.1016/S0140-6736(14)61601-9] [PMID: 25777665]
[3]
Vanholder R, Van Laecke S, Glorieux G, Verbeke F, Castillo-Rodriguez E, Ortiz A. Deleting death and dialysis: Conservative care of cardio-vascular risk and kidney function loss in chronic kidney disease (CKD). Toxins (Basel) 2018; 10(6): 237.
[http://dx.doi.org/10.3390/toxins10060237] [PMID: 29895722]
[4]
Takasato M, Little MH. A strategy for generating kidney organoids: Recapitulating the development in human pluripotent stem cells. Dev Biol 2016; 420(2): 210-20.
[http://dx.doi.org/10.1016/j.ydbio.2016.08.024] [PMID: 27565022]
[5]
Morizane R, Bonventre JV. Generation of nephron progenitor cells and kidney organoids from human pluripotent stem cells. Nat Protoc 2017; 12(1): 195-207.
[http://dx.doi.org/10.1038/nprot.2016.170] [PMID: 28005067]
[6]
Grassi L, Alfonsi R, Francescangeli F, et al. Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases. Cell Death Dis 2019; 10(3): 201.
[http://dx.doi.org/10.1038/s41419-019-1453-0] [PMID: 30814510]
[7]
Kaushik G, Ponnusamy MP, Batra SK. Current status of 3-D organoids as pre-clinical models. Stem Cells 2018; 36: 1329-40.
[http://dx.doi.org/10.1002/stem.2852] [PMID: 29770526]
[8]
Lam AQ, Freedman BS, Bonventre JV. Directed differentiation of pluripotent stem cells to kidney cells. Semin Nephrol 2014; 34(4): 445-61.
[http://dx.doi.org/10.1016/j.semnephrol.2014.06.011] [PMID: 25217273]
[9]
Yamaguchi S, Morizane R, Homma K, et al. Generation of kidney tubular organoids from human pluripotent stem cells. Sci Rep 2016; 6(1): 38353.
[http://dx.doi.org/10.1038/srep38353] [PMID: 27982115]
[10]
van den Berg CW, Ritsma L, Avramut MC, et al. Renal subcapsular transplantation of psc-derived kidney organoids induces neo-vasculogenesis and significant glomerular and tubular maturation In Vivo. Stem Cell Reports 2018; 10(3): 751-65.
[http://dx.doi.org/10.1016/j.stemcr.2018.01.041] [PMID: 29503086]
[11]
Urie BK, Tillson DM, Smith CM, et al. Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors. J Am Vet Med Assoc 2007; 230(11): 1653-6.
[http://dx.doi.org/10.2460/javma.230.11.1653] [PMID: 17542732]
[12]
Kendi Celebi Z, Peker A, Kutlay S, et al. Effect of unilateral nephrectomy on urinary angiotensinogen levels in living kidney donors: 1 year follow-up study. J Renin Angiotensin Aldosterone Syst 2017; 18(4)1470320317734082
[http://dx.doi.org/10.1177/1470320317734082] [PMID: 28988519]
[13]
Zhang D, Du X, Zhang X, et al. In vitro induction and in vivo engraftment of kidney organoids derived from human pluripotent stem cells. Exp Ther Med 2020; 20(2): 1307-14.
[http://dx.doi.org/10.3892/etm.2020.8844] [PMID: 32742364]
[14]
Hyodo T, Naguro T, Kameie T, Iino A, Miyagawa I. Scanning and transmission electron-microscopic study of the development of the podocyte in the human fetus. Pediatr Nephrol 1997; 11(2): 133-9.
[http://dx.doi.org/10.1007/s004670050244] [PMID: 9090649]
[15]
Dekel B, Shezen E, Even-Tov-Friedman S, et al. Transplantation of human hematopoietic stem cells into ischemic and growing kidneys suggests a role in vasculogenesis but not tubulogenesis. Stem Cells 2006; 24(5): 1185-93.
[http://dx.doi.org/10.1634/stemcells.2005-0265] [PMID: 16410390]
[16]
Hammerman MR. Pancreas and kidney transplantation using embryonic donor organs. Organogenesis 2004; 1(1): 3-13.
[http://dx.doi.org/10.4161/org.1.1.1008] [PMID: 19521554]
[17]
Combes AN, Zappia L, Er PX, Oshlack A, Little MH. Single-cell analysis reveals congruence between kidney organoids and human fetal kidney. Genome Med 2019; 11(1): 3.
[http://dx.doi.org/10.1186/s13073-019-0615-0] [PMID: 30674341]
[18]
Przepiorski A, Sander V, Tran T, et al. A simple bioreactor-based method to generate kidney organoids from Pluripotent stem cells. Stem Cell Reports 2018; 11(2): 470-84.
[http://dx.doi.org/10.1016/j.stemcr.2018.06.018] [PMID: 30033089]
[19]
The impact of kidney development on the life course: A consensus document for action. Nephron 2017; 136(1): 3-49.
[http://dx.doi.org/10.1159/000457967] [PMID: 28319949]
[20]
Matsumoto K, Yokoo T, Yokote S, Utsunomiya Y, Ohashi T, Hosoya T. Functional development of a transplanted embryonic kidney: Effect of transplantation site. J Nephrol 2012; 25(1): 50-5.
[http://dx.doi.org/10.5301/JN.2011.7426] [PMID: 21500184]
[21]
Roy A, Al-bataineh MM, Pastor-Soler NM. Collecting duct intercalated cell function and regulation. Clin J Am Soc Nephrol 2015; 10(2): 305-24.
[http://dx.doi.org/10.2215/CJN.08880914] [PMID: 25632105]
[22]
Takasato M, Little MH. The origin of the mammalian kidney: Implications for recreating the kidney in vitro. Development 2015; 142(11): 1937-47.
[http://dx.doi.org/10.1242/dev.104802] [PMID: 26015537]
[23]
Sharmin S, Taguchi A, Kaku Y, et al. Human induced pluripotent stem cell-derived podocytes mature into vascularized glomeruli upon experimental transplantation. J Am Soc Nephrol 2016; 27(6): 1778-91.
[http://dx.doi.org/10.1681/ASN.2015010096] [PMID: 26586691]
[24]
Kim JW, Nam SA, Yi J, et al. 2022. Kidney decellularized extracellular matrix enhanced the vascularization and maturation of human kidney organoids. Adv Sci (Weinh) 2022; 9(15)
[http://dx.doi.org/10.1002/advs.202103526,]

Rights & Permissions Print Cite
Article Metrics
37
2
© 2024 Bentham Science Publishers | Privacy Policy