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Delivery system for autologous growth factors fabricated with low-molecular-weight heparin and protamine to attenuate ischemic hind-limb loss in a mouse model

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Abstract

Frozen and thawed platelet-rich plasma (PRP) contains high concentrations of various growth factors, such as fibroblast growth factor (FGF)-2, vascular endothelial growth factor, and hepatocyte growth factor. We previously reported that low-molecular-weight heparin/protamine microparticles (LH/P MPs) are useful as biodegradable carriers for the controlled release of FGF-2. In this study, we examined the ability of PRP/LH/P MPs to prevent limb loss in an induced ischemic hind-limb model that used adult BALB/c-nu/nu male mice. One day after inducing ischemia, intramuscular injections of a PRP/LH/P MPs solution were administered into several sites of the ischemic hind limb. Seven days and onward after the injections, the PRP/LH/P MPs-treated and PRP-treated groups recovered from ischemia, as reflected by the improved oxygen saturation. In the PRP-treated group, however, the level of recovery of oxygen saturation after ischemia decreased after 14 days. From the 21st day onward, there was a significant difference between those two groups. In the LH/P MPs-treated group, a partial recovery occurred only in the early period. The saline-treated group (i.e., the control) and the noninjection group (i.e., ischemia only) exhibited no recovery. The limb survival rate at 1 year in the ischemia-induced mice injected with PRP/LH/P MPs was approximately 25 % (two of eight mice) but was absent in the other groups.

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Acknowledgments

We thank Dr. Koichi Fukuda (Center for Laboratory Animal Science, National Defense Medical College) for his support in the animal experiments, and Dr. Yoshihiro Tanaka (National Defense Medical College) for the discussion. This work was supported by Grant-in-Aid for Young Scientists (B) (Grant No. 22780274) from the Ministry of Education, Science, Sports, Culture, and Technology of Japan.

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Authors and Affiliations

  1. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Shingo Nakamura, Takefumi Nakayama, Susumu Isoda, Yuichi Ozeki & Tadaaki Maehara

  2. Department of Plastic Surgery, National Defense Medical College, Saitama, 359-8513, Japan

    Megumi Takikawa

  3. Research Institute, National Defense Medical College, Saitama, 359-8513, Japan

    Masayuki Ishihara & Satoko Kishimoto

  4. Section of Gene Expression Regulation, Frontier Science Research Center, Kagoshima University, 1-21-40 Kohrimoto, Kagoshima, Kagoshima, 890-0065, Japan

    Masahiro Sato

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  1. Shingo Nakamura
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  2. Megumi Takikawa
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Correspondence to Shingo Nakamura or Tadaaki Maehara.

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Nakamura, S., Takikawa, M., Ishihara, M. et al. Delivery system for autologous growth factors fabricated with low-molecular-weight heparin and protamine to attenuate ischemic hind-limb loss in a mouse model. J Artif Organs 15, 375–385 (2012). https://doi.org/10.1007/s10047-012-0658-0

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  • DOI: https://doi.org/10.1007/s10047-012-0658-0

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