Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering
Open accessAbstract
Despite the enthusiasm for bioengineering of functional renal tissues for transplantation, many obstacles remain before the potential of this technology can be realized in a clinical setting. Viable tissue engineering strategies for the kidney require identification of the necessary cell populations, efficient scaffolds, and the 3D culture conditions to develop and support the unique architecture and physiological function of this vital organ. Our studies have previously demonstrated that decellularized sections of rhesus monkey kidneys of all age groups provide a natural extracellular matrix (ECM) with sufficient structural properties with spatial and organizational influences on human embryonic stem cell (hESC) migration and differentiation. To further explore the use of decellularized natural kidney scaffolds for renal tissue engineering, pluripotent hESC were seeded in whole- or on sections of kidney ECM and cell migration and phenotype compared with the established differentiation assays for hESC. Results of qPCR and immunohistochemical analyses demonstrated upregulation of renal lineage markers when hESC were cultured in decellularized scaffolds without cytokine or growth factor stimulation, suggesting a role for the ECM in directing renal lineage differentiation. hESC were also differentiated with growth factors and compared when seeded on renal ECM or a new biologically inert polysaccharide scaffold for further maturation. Renal lineage markers were progressively upregulated over time on both scaffolds and hESC were shown to express signature genes of renal progenitor, proximal tubule, endothelial, and collecting duct populations. These findings suggest that natural scaffolds enhance expression of renal lineage markers particularly when compared to embryoid body culture. The results of these studies show the capabilities of a novel polysaccharide scaffold to aid in defining a protocol for renal progenitor differentiation from hESC, and advance the promise of tissue engineering as a source of functional kidney tissue.
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Decellularization approaches have been demonstrated for human kidney, murine kidney, murine heart, human and porcine lung, and porcine testicular tissues.
“Decellularization approaches have been demonstrated for human kidney67, murine kidney67,68, murine heart69,70, human and porcine lung71, and porcine testicular72 tissues, with each type posing unique challenges.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [68]
Some organoids have been grown in decellularized ECM from human or animal donors.
“In order to accurately recapitulate the composition, structure, and vascularization of native ECM in organ development, some organoids have been grown in decellularized ECM from human or animal donors.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [68]
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References 53 · Cited by 77
Research works printed but not linked: 2
- [31]Caralt M, Uzarski JS, Iacob S, Obergfell KP, Berg N, Bijonowski BM, et al Optimization and critical evaluation of decellularization strategies to develop renal extracellular matrix scaffolds as biological templates for organ engineering and transplantation. Am J Transplant 2015; 15: 64– 75. 10.1111/ajt.12999 25403742 PMC4276475 · DOI
- [33]Petrosyan A, Orlando G, Peloso A, Wang Z, Farney AC, Rogers J, Katari R, et al Understanding the bioactivity of stem cells seeded on extracellular matrix scaffolds produced from discarded human kidneys: a critical step towards a new generation bio-artificial kidney. CellR4 2015; 3: e1401.
- Authors
- Batchelder, C. A., Martinez, M. L., & Tarantal, A. F.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Tarantal, Alice F.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-12-08
- Volume
- 10
- Issue
- 12
- Pages
- e0143849
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4672934
- OpenAlex
- W2192802072
- Cited by
- 77
- References
- 53
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 4 · 2021: 12 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 7 · 2016: 6
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (1s10od016261-01, 1s10od018102-01, P51OD011107)
- University of California, Davis
- National Center for Research Resources (S10RR025063)
- California National Primate Research Center (OD 011107, P51OD011107)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- kidney tissue engineering, human embryonic stem cells, extracellular matrix, renal differentiation, renal progenitor cells, polysaccharide scaffolds, 3D cell culture, kidney transplantation, proximal tubule, collecting duct, endothelial cells
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Humans, Kidney, Macaca mulatta, Tissue Engineering, Embryonic Stem Cells, Tissue Scaffolds
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