TY - JOUR AU - Takebe, Takanori AU - Kobayashi, Shinji AU - Suzuki, Hiromu AU - Mizuno, Mitsuru AU - Chang, Yu-Min AU - Yoshizawa, Emi AU - Kimura, Masaki AU - Hori, Ayaka AU - Asano, Jun AU - Maegawa, Jiro AU - Taniguchi, Hideki T1 - Transient vascularization of transplanted human adult–derived progenitors promotes self-organizing cartilage PY - 2014/10/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI76443 VL - 124 IS - 10 UR - https://doi.org/10.1172/JCI76443 SP - 4325 EP - 4334 PB - The American Society for Clinical Investigation ER -