title: Biomedical application of low molecular weight heparin/protamine nano/micro particles as cell- and growth factor-carriers and coating matrix.
abstract: Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm-3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.
authors.affiliation: Division of Biomedical Engineering Research Institute, National Defense Medical College, Saitama 359-8513, Japan. ishihara@ndmc.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Research Support Center, Dokkyo Medical University, Tochigi 321-0293, Japan. skishi@dokkyomed.ac.jp.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kishimoto
authors.affiliation: Department of Medical Engineering, National Defense Medical College, Saitama 359-8513, Japan. drme003@ndmc.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takikawa
authors.affiliation: Division of Biomedical Engineering Research Institute, National Defense Medical College, Saitama 359-8513, Japan. h2@ndmc.ac.jp.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hattori
authors.affiliation: Division of Biomedical Engineering Research Institute, National Defense Medical College, Saitama 359-8513, Japan. snaka@ndmc.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Surgery, Tokorozawa Meisei Hospital, Saitama 359-1145, Japan. masafumi@tokorozawameisei.or.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D053657:Platelet-Rich Plasma / Q000737:chemistry; D011479:Protamines / Q000737:chemistry*; D051381:Rats; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D006495:Heparin, Low-Molecular-Weight; D036341:Intercellular Signaling Peptides and Proteins; D011479:Protamines
keywords: adipose-derived stromal cells; bone marrow-derived mesenchymal stem cells; cell delivery systems; coating matrix; nano/micro particles