Delivery system for autologous growth factors fabricated with low-molecular-weight heparin and protamine to attenuate ischemic hind-limb loss in a mouse model.
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.
Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan. snaka@ndmc.ac.jp
Shingo
S
Nakamura
Megumi
M
Takikawa
Masayuki
M
Ishihara
Takefumi
T
Nakayama
Satoko
S
Kishimoto
Susumu
S
Isoda
Yuichi
Y
Ozeki
Masahiro
M
Sato
Tadaaki
T
Maehara
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006494:Heparin Antagonists / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D023821:Limb Salvage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011479:Protamines / Q000008:administration & dosage*
D000925:Anticoagulants; D006494:Heparin Antagonists; D006495:Heparin, Low-Molecular-Weight; D011479:Protamines; D016222:Fibroblast Growth Factor 2