Implantation of bone marrow mononuclear cells using injectable fibrin matrix enhances neovascularization in infarcted myocardium.
Neovascularization may improve cardiac function and prevent further scar tissue formation in infarcted myocardium. A number of studies have demonstrated that bone marrow-derived cells have the potential to induce neovascularization in ischemic tissues. In this study, we hypothesized that implantation of bone marrow mononuclear cells (BMMNCs) using injectable fibrin matrix further enhances neovascularization in infarcted myocardium compared to BMMNC implantation without matrix. To test this hypothesis, infarction was induced in rat myocardium by cryoinjury. Three weeks later, rat BMMNCs were mixed with fibrin matrix and injected into the infarcted myocardium. Injection of either BMMNCs or medium alone into infarcted myocardium served as controls. Eight weeks after the treatments, histological analyses indicated that implantation of BMMNCs using fibrin matrix resulted in more extensive tissue regeneration in the infarcted myocardium compared to BMMNC implantation without matrix. Examination with fluorescence microscopy revealed that cells labeled with a fluorescent dye prior to implantation survived in the infarcted myocardium at 8 weeks of implantation. Importantly, implantation of BMMNCs using fibrin matrix resulted in much more extensive neovascularization in infarcted myocardium than BMMNC implantation without matrix. The microvessel density in infarcted myocardium was significantly higher (p < 0.05) when BMMNCs were implanted using fibrin matrix (350 +/- 22 microvessels/mm2) compared to BMMNC implantation without matrix (262 +/- 13 microvessels/mm2) and medium injection (76 +/- 9 microvessels/mm2). In addition, average internal diameter of microvessels was significantly larger (p < 0.05) in BMMNC implantation with fibrin matrix group (14.6 +/- 1.2 microm) than BMMNC implantation without matrix group (10.2 +/- 0.7 microm) and medium injection group (7.3 +/- 0.5 microm). These results suggest that fibrin matrix could serve as a cell implantation matrix that enhances neovascularization efficacy for myocardial infarction treatment.
Ryu
Ju Hee
JH
Department of Chemical Engineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, South Korea.
Kim
Il-Kwon
IK
Cho
Seung-Woo
SW
Cho
Myeong-Chan
MC
Hwang
Kyung-Kuk
KK
Piao
Hainan
H
Piao
Shuguang
S
Lim
Sang Hyun
SH
Hong
Yoo Sun
YS
Choi
Cha Yong
CY
Yoo
Kyung Jong
KJ
Kim
Byung-Soo
BS
D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry; D016026:Bone Marrow Transplantation / Q000379:methods*; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology; D005337:Fibrin / Q000008:administration & dosage*; D007267:Injections; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D009000:Monocytes / Q000473:pathology* / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D005337:Fibrin