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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 Stem cells

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 3

Protocol optimization for growing prevascularized condensation from human progenitor cells.

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Protocol optimization for growing prevascularized condensation from huma...
(A) Comparison between Matrigel-precoated and normal cell culture plates on which hCPC single cultures or hCPC and endothelial cell cocultures were plated, showing that Matrigel presolidification was essential to induce the 3D condensation of hCPCs and HUVECs. Scale bar: 2 mm. (B) Confocal imaging of in vitro–generated condensed tissue at day 4. Green indicates HUVECs; red indicates hCPCs. Scale bar: 750 μm. (C) Protocol optimization of the hCPC and HUVEC mixing ratio for the regeneration of human cartilage. See also Supplemental Figure 3. *P < 0.01 by Mann-Whitney U test with Bonferroni’s correction.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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