Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

International Journal of Molecular Sciences

Masayuki Ishihara³  Satoko Kishimoto⁴  Makoto Takikawa²  Hidemi Hattori³  Shingo Nakamura³  Masafumi Shimizu¹ 

[1] Department of Surgery, Tokorozawa Meisei Hospital, Saitama 359-1145, Japan; E-Mail:;Department of Medical Engineering, National Defense Medical College, Saitama 359-8513, Japan; E-Mail:;Division of Biomedical Engineering Research Institute, National Defense Medical College, Saitama 359-8513, Japan; E-Mails:;Research Support Center, Dokkyo Medical University, Tochigi 321-0293, Japan; E-Mail:

关键词: adipose-derived stromal cells;    bone marrow-derived mesenchymal stem cells;    nano/micro particles;    coating matrix;    cell delivery systems;   

DOI  :  10.3390/ijms160511785

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.