Fragmin/protamine microparticles as cell carriers to enhance viability of adipose-derived stromal cells and their subsequent effect on in vivo neovascularization.
We prepared fragmin/protamine microparticles (F/P MPs) as cell carriers to enhance cell viability. Use of material consisting of a low-molecular-weight heparin (fragmin) mixed with protamine resulted in water-insoluble microparticles (about 0.5-1 microm in diameter). In this study, we investigated the capability of F/P MPs to enhance the viabilities of human microvascular endothelial cells (HMVECs), human dermal fibroblasts (fibroblasts), and adipose tissue-derived stromal cells (ATSCs) in suspension culture. F/P MPs were bound to the surfaces of these cells, and the interaction of these cells with F/P MPs induced cells/F/P MPs-aggregate formations in vitro, and maintained viabilities of those cells for at least 3 days. The ATSCs/F/P MPs-aggregates adhered to and grew on suspension culture plates in a fashion similar to those on type I collagen-coated plates. The cultured ATSCs secreted significant amounts of angiogenic heparin-binding growth factors such as FGF-2. When the ATSCs/F/P MPs-aggregates were subcutaneously injected into the back of nude mice, significant neovascularization and fibrous tissue formation were induced near the site of injection from day 3 to week 2. The ATSCs/F/P MPs-aggregates were thus useful and convenient biomaterials for cell-therapy of angiogenesis.
Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan. snaka@ndmc.ac.jp
Shingo
S
Nakamura
Satoko
S
Kishimoto
Shin-ichiro
S
Nakamura
Masaki
M
Nambu
Masanori
M
Fujita
Yoshihiro
Y
Tanaka
Yasutaka
Y
Mori
Masahiro
M
Tagawa
Tadaaki
T
Maehara
Masayuki
M
Ishihara
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D017985:Dalteparin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D011479:Protamines / Q000737:chemistry* / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*
D001672:Biocompatible Materials; D036341:Intercellular Signaling Peptides and Proteins; D011479:Protamines; D017985:Dalteparin