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Am J Transl Res 2013;5(2):155-169

Original Article
Transplantation of bone marrow derived monocytes: a novel approach
for augmentation of arteriogenesis in a murine model of femoral artery

Alexander Francke, Soenke Weinert, Ruth H Strasser, Ruediger C Braun-Dullaeus, Joerg Herold

Department of Internal Medicine / Cardiology, Herzzentrum Dresden GmbH Universitätsklinik, Fetscherstrasse
76, D-01307 Dresden; Universitätsklinik für Kardiologie, Angiologie und Pneumologie, Universitätsklinikum
Magdeburg, Leipziger Str. 44, 39120 Magdeburg

Received January 16, 2013; Accepted February 1, 2013; Epub March 28, 2013; Published April 8, 2013

Abstract: Therapeutic augmentation of collateral artery growth (arteriogenesis) is of tremendous clinical interest.
Since monocytes home to areas of arteriogenesis and create a local arteriogeneic milieu by secreting a wide
range of growth factors, we followed the idea of utilizing these cells for augmentation of collateral growth. For that
purpose, we adoptively transferred both syngeneic (same strain) and allogeneic (different strain) bone marrow
derived monocytes (BMDMs) into balb/c mice 24 h after femoral artery ligation. Restoration of hind-limb perfusion
was determined by Laser Doppler Perfusion Imaging and histological workup. While syngeneic cell
transplantation did not augment arteriogenesis in comparison to non-transplanted animals (PI = 0.56 ± 0.06 vs.
0.48 ± 0.09, respectively, ns), allogeneic monocytes massively promoted the collateralization (PI = 0.85 ± 0.14, p <
0.001). Homed monocytes were visualized near growing collateral vessels by staining the cells with the lipophil
fluorochrome DiI prior to transplantation. To analyze whether the effect of allogeneic BMDM transplantations is
due to local inflammation triggered by a host-versus-graft reaction, transplant recipients were pre-treated with the
immunosuppressive drug cyclosporine A, which completely prevented the effect of allogeineic monocyte
transplantation (PI = 0.45 ± 0.06, p < 0.001). Here, we have demonstrated murine allogeneic monocytes to be an
attractive way to trigger local inflammatory responses near growing collateral vessels and stimulate their
adaption, overcoming the endogenous restriction of collateral vessel growth (AJTR1302009).

Keywords: Monocyte, cell transplantation, collateral circulation, immune system, vascular biology

Address correspondence to: Dr. Joerg Herold, Internal Medicine/Cardiology, Angiology and Pneumology,
Magdeburg University, Leipziger Strasse 44, 39120 Magdeburg, Germany. Phone: +49-391-6713203; Fax:
+49-391-6713202; E-mail: joerg_herold@hotmail.com