Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in three-dimensional co-culture

Chakradhar Velagapudi, Rune Par Nilsson, Myung Ja Lee, Hannah S. Burns, Jill M. Ricono, Mazen Y Arar, Veronique L. Barnes, Hanna E. Abboud, Jeffrey L. Barnes

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Kidney development is regulated by a coordinated reciprocal induction of metanephric mesenchymal (MM) and ureteric bud (UB) cells. Here, established MM and UB progenitor cell lines were recombined in three-dimensional Matrigel implants in SCID mice. Differentiation potential was examined for changes in phenotype, organization, and the presence of specialized proteins using immunofluorescence and bright-field and electron microscopy. Both cell types, when grown alone, did not develop into specialized structures. When combined, the cells organized into simple organoid structures of polarized epithelia with lumens surrounded by capillary-like structures. Tracker experiments indicated the UB cells formed the tubuloid structures, and the MM cells were the source of the capillary-like cells. The epithelial cells stained positive for pancytokeratin, the junctional complex protein ZO-1, collagen type IV, as well as UB and collecting duct markers, rearranged during transfection (RET), Dolichos biflorus lectin, EndoA cytokeratin, and aquaporin 2. The surrounding cells expressed α-smooth muscle actin, vimentin, platelet endothelial cell adhesion molecule 1 (PECAM), and aquaporin 1, a marker of vasculogenesis. The epithelium exhibited apical vacuoles, microvilli, junctional complexes, and linear basement membranes. Capillary-like structures showed endothelial features with occasional pericytes. UB cell epithelialization was augmented in the presence of MM cellderived conditioned medium, glial-derived neurotrophic factor (GDNF), hepatocyte growth factor (HGF), or fibronectin. MM cells grown in the presence of UB-derived conditioned medium failed to undergo differentiation. However, UB cellderived conditioned medium induced MM cell migration. These studies indicate that tubulogenesis and vasculogenesis can be partially recapitulated by recombining individual MM and UB cell lineages, providing a new model system to study organogenesis ex vivo.

Original languageEnglish (US)
Pages (from-to)819-830
Number of pages12
JournalAmerican Journal of Pathology
Volume180
Issue number2
DOIs
StatePublished - Feb 2012

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Organogenesis
Coculture Techniques
Stem Cells
Kidney
Conditioned Culture Medium
Keratin-2
Epithelium
Aquaporin 2
Aquaporin 1
Organoids
CD31 Antigens
Pericytes
Hepatocyte Growth Factor
SCID Mice
Collagen Type IV
Nerve Growth Factors
Vimentin
Cell Lineage
Microvilli
Vacuoles

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in three-dimensional co-culture. / Velagapudi, Chakradhar; Nilsson, Rune Par; Lee, Myung Ja; Burns, Hannah S.; Ricono, Jill M.; Arar, Mazen Y; Barnes, Veronique L.; Abboud, Hanna E.; Barnes, Jeffrey L.

In: American Journal of Pathology, Vol. 180, No. 2, 02.2012, p. 819-830.

Research output: Contribution to journalArticle

Velagapudi, C, Nilsson, RP, Lee, MJ, Burns, HS, Ricono, JM, Arar, MY, Barnes, VL, Abboud, HE & Barnes, JL 2012, 'Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in three-dimensional co-culture', American Journal of Pathology, vol. 180, no. 2, pp. 819-830. https://doi.org/10.1016/j.ajpath.2011.11.002
Velagapudi, Chakradhar ; Nilsson, Rune Par ; Lee, Myung Ja ; Burns, Hannah S. ; Ricono, Jill M. ; Arar, Mazen Y ; Barnes, Veronique L. ; Abboud, Hanna E. ; Barnes, Jeffrey L. / Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in three-dimensional co-culture. In: American Journal of Pathology. 2012 ; Vol. 180, No. 2. pp. 819-830.
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