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Transient vascularization of transplanted human adult–derived progenitors promotes self-organizing cartilage
Takanori Takebe, … , Jiro Maegawa, Hideki Taniguchi
Takanori Takebe, … , Jiro Maegawa, Hideki Taniguchi
Published September 9, 2014
Citation Information: J Clin Invest. 2014;124(10):4325-4334. https://doi.org/10.1172/JCI76443.
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Technical Advance Article has an altmetric score of 6

Transient vascularization of transplanted human adult–derived progenitors promotes self-organizing cartilage

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Abstract

Millions of patients worldwide are affected by craniofacial deformations caused by congenital defects or trauma. Current surgical interventions have limited therapeutic outcomes; therefore, methods that would allow cartilage restoration are of great interest. A number of studies on embryonic limb development have shown that chondrogenesis is initiated by cellular condensation, during which mesenchymal progenitors aggregate and form 3D structures. Here, we demonstrated efficient regeneration of avascular elastic cartilage from in vitro–grown mesenchymal condensation, which recapitulated the early stages of chondrogenesis, including transient vascularization. After transplantation of vascularized condensed progenitors into immunodeficient mice, we used an intravital imaging approach to follow cartilage maturation. We determined that endothelial cells are present inside rudimentary cartilage (mesenchymal condensation) prior to cartilage maturation. Recreation of endothelial interactions in culture enabled a recently identified population of adult elastic cartilage progenitors to generate mesenchymal condensation in a self-driven manner, without requiring the support of exogenous inductive factors or scaffold materials. Moreover, the culture-grown 3D condensed adult–derived progenitors were amenable to storage via simple freezing methods and efficiently reconstructed 3D elastic cartilage upon transplantation. Together, our results indicate that transplantation of endothelialized and condensed progenitors represents a promising approach to realizing a regenerative medicine treatment for craniofacial deformations.

Authors

Takanori Takebe, Shinji Kobayashi, Hiromu Suzuki, Mitsuru Mizuno, Yu-Min Chang, Emi Yoshizawa, Masaki Kimura, Ayaka Hori, Jun Asano, Jiro Maegawa, Hideki Taniguchi

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Figure 1

Rudimentary ear cartilage (mesenchymal condensation) is transiently vascularized in vivo.

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Rudimentary ear cartilage (mesenchymal condensation) is transiently vasc...
(A) Gross observations of E18.5 CAG-EGFP murine immature cartilage transplants at multiple time points. (B) Immunohistological analyses of mCD31 and laminins in ear cartilage from P0 to P30. Dotted line indicates the border between the chondral and perichondral layers of the mouse ear cartilage. Scale bar: 50 μm. (C) Intravital confocal images of the same field of view at 3, 7, and 10 days after transplantation. Arrowhead indicates the vascularized area of the transplants. Endothelial cells and blood perfusion were visualized intravitally using Alexa Fluor 647–conjugated mCD31 antibody and fluorophore-conjugated dextran injected via the tail vein. Scale bars: 75 μm. (D) Formation of mature cartilage 20 days after transplantation. The developed chondral layer was composed of homogenous polygonal mature chondrocytes, whereas the perichondrium (double-headed arrow, outer fibrous layer) was composed of spindle-shaped putative progenitor cells that were proximate to blood vessels, similar to normal ear cartilage. Scale bars: 200 μm (top and middle panels) and 25 μm (bottom panel). (E) Terminal differentiation from murine progenitor cells into mature chondrocytes after transplantation into a cranial window. Alcian blue and EVG staining confirmed the formation of mature elastic cartilage from E18.5 immature cartilage transplants after 20 days compared with E18.5 and P30 cartilage sections. Tx; transplantation. Scale bars: 100 μm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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