title: Calcium phosphate glass improves angiogenesis capacity of poly(lactic acid) scaffolds and stimulates differentiation of adipose tissue-derived mesenchymal stromal cells to the endothelial lineage.
abstract: The angiogenic capacity of a new biomaterial composite of poly(lactic acid) and calcium phosphate glass (PLA/CaP) was analyzed by noninvasive bioluminescence imaging (BLI) and histological procedures. Human adipose tissue-derived mesenchymal stromal cells expressing cytomegalovirus (CMV) promoter regulated Photinus pyralis luciferase (hAMSC-PLuc) grew up to 30 times the initial cell load, in vitro, when seeded in PLA/CaP scaffolds, but suffered an initial growth crisis followed by recovery when the scaffolds were subcutaneously implanted in SCID mice. To analyze changes in gene expression, hAMSC-PLuc cells were double labeled with a CMV promoter regulated Renilla reniformis luciferase and a Photinus pyralis luciferase reporter regulated by either the PECAM promoter or a hypoxia response element (HRE) artificial promoter and seeded in PLA/CaP and PLA scaffolds implanted in SCID mice. Analysis by BLI showed that hAMSCs in scaffolds were induced to differentiate to the endothelial lineage and did this faster in PLA/CaP than in PLA scaffolds. Endothelial differentiation correlated with a decrease in the activity of HRE regulated luciferase expression, indicative of a reduction of hypoxia. Histological analysis showed that PLA/CaP scaffolds were colonized by a functional host vascular system. Moreover, colonization by isolectin B(4) positive host cells was more effective in PLA/CaP than in PLA scaffolds, corroborating BLI results.
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC-UAB), Barcelona, Spain.
authors.forename: Olaia F
authors.initials: OF
authors.lastname: Vila
authors.forename: Juli R
authors.initials: JR
authors.lastname: Bagó
authors.forename: Melba
authors.initials: M
authors.lastname: Navarro
authors.forename: Maria
authors.initials: M
authors.lastname: Alieva
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aguilar
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Engel
authors.forename: Josep
authors.initials: J
authors.lastname: Planell
authors.forename: Nuria
authors.initials: N
authors.lastname: Rubio
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Blanco
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005898:Glass / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D002130:Calcium Phosphates; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); C020243:calcium phosphate