title: Transient vascularization of transplanted human adult-derived progenitors promotes self-organizing cartilage.
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.forename: Takanori
authors.initials: T
authors.lastname: Takebe
authors.forename: Shinji
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Mizuno
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Chang
authors.forename: Emi
authors.initials: E
authors.lastname: Yoshizawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hori
authors.forename: Jun
authors.initials: J
authors.lastname: Asano
authors.forename: Jiro
authors.initials: J
authors.lastname: Maegawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D017690:Cell Transplantation / Q000379:methods*; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D015925:Cryopreservation; D005615:Freezing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D046509:Tissue Culture Techniques / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D049452:Green Fluorescent Proteins