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Retinoic Acid Benefits Glomerular Organotypic Differentiation from Adult Renal Progenitor Cells In Vitro

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Summary

When in certain culture conditions, organotypic cultures are able to mimic developmental stages of an organ, generating higher-order structures containing functional subunits and progenitor niches. Despite the major advances in the area, researchers have not been able to fully recapitulate the complexity of kidney tissue. Pluripotent stem cells are extensively used in the field, but very few studies make use of adult stem cells. Herein, we describe a simple and feasible method for achieving glomerular epithelial differentiation on an organotypic model comprising human renal progenitor cells from adult kidney (hRPCs). Their glomerular differentiative potential was studied using retinoic acid (RA), a fundamental molecule for intermediate mesoderm induction on early embryogenesis. Immunofluorescence, specific cell surface markers expression and gene expression analysis confirm the glomerular differentiative potential of RA in a short-term culture. We also compared the potential of RA with a potent WNT agonist, CHIR99021, on the differentiative capacity of hRPCs. Gene expression and immunofluorescence analysis confirmed that hRPCs are more sensitive to RA stimulation when compared to CHIR9901. Endothelial cells were also included on the spheroids, resulting in a higher organizational level. The assembly potential of these cells and their selective stimulation will give new insights on adult organotypic cell culture studies and will hopefully guide more works in this important area of research.

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Availability of Data and Material

Derived data supporting the findings of this study are available from the corresponding author (N.N.) on request.

Funding

This work was supported by the Portuguese Foundation of Technology (FCT) with the PhD Grant on the Doctoral Program on Advanced Therapies for Health (PATH) (PD/BD/128102/2016) and the the project Cells4_IDs (PTDC/BTM-SAL/28882/2017), under the Compete2020 Funding Program.

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Authors and Affiliations

  1. 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal

    Rita Sobreiro-Almeida & Nuno M. Neves

  2. ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Rita Sobreiro-Almeida & Nuno M. Neves

  3. Department of Biomedical, Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Maria Elena Melica, Laura Lasagni & Paola Romagnani

  4. Nephrology and Dialysis Unit, Meyer Children’s University Hospital, Florence, Italy

    Paola Romagnani

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  1. Rita Sobreiro-Almeida
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Contributions

Conceptualization, Rita Sobreiro-Almeida, Maria Elena Melica and Laura Lasagni; Methodology, Rita Sobreiro-Almeida and Maria Elena Melica; Investigation, Rita Sobreiro-Almeida and Maria Elena Melica; Writing – Original Draft, Rita Sobreiro-Almeida; Writing – Review & Editing, Nuno M. Neves and Laura Lasagni; Funding Acquisition, Nuno M. Neves and Paola Romagnani; Resources, Nuno M. Neves and Paola Romagnani; Supervision, Nuno M. Neves, Laura Lasagni and Paola Romagnani.

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Correspondence to Nuno M. Neves.

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The authors have no relevant financial or non-financial interests to disclose.

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Renal progenitor cells were obtained from the digestion of human kidney fragments. These were obtained in agreement with the Ethical Committee on human experimentation of the Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee on Human Experimentation of the Azienda Ospedaliero-Universitaria Careggi, Florence, Italy (project identification code 2015/0009082 from 25/03/2015).

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Sobreiro-Almeida, R., Melica, M.E., Lasagni, L. et al. Retinoic Acid Benefits Glomerular Organotypic Differentiation from Adult Renal Progenitor Cells In Vitro. Stem Cell Rev and Rep 17, 1406–1419 (2021). https://doi.org/10.1007/s12015-021-10128-8

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