Thorac Cardiovasc Surg 2010; 58(3): 136-142
DOI: 10.1055/s-0029-1240758
Original Cardiovascular

© Georg Thieme Verlag KG Stuttgart · New York

Angiogenic Effects Despite Limited Cell Survival of Bone Marrow-Derived Mesenchymal Stem Cells under Ischemia

J. Hoffmann1 , A. J. Glassford2 , T. C. Doyle3 , R. C. Robbins1 , S. Schrepfer1 , M. P. Pelletier1
  • 1Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, United States
  • 2Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States
  • 3Small Animal Imaging Facility, Stanford University School of Medicine, Stanford, CA, United States
Further Information

Publication History

received March 18, 2009

Publication Date:
08 April 2010 (online)

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent and secrete angiogenic factors, which could help patients with occlusive arterial diseases. We hypothesize that MSCs, in comparison to fibroblasts, survive better under hypoxic conditions in vitro and in vivo. MSCs and fibroblasts from L2G mice expressing firefly luciferase and GFP were cultured in normoxic and hypoxic conditions for 24 hours. In vitro cell viability was tested by detecting apoptosis and necrosis. MSCs released higher amounts of VEGF (281.1 ± 62.6 pg/ml) under hypoxic conditions compared to normoxia (154.9 ± 52.3 pg/ml, p = NS), but were less tolerant to hypoxia (45 ± 7.9 %) than fibroblasts (28.1 ± 3.6 %, p = NS). A hindlimb ischemia model was created by ligating the femoral artery of 18 FVB mice. After one week, 1 × 106 cells (MSCs, fibroblasts or saline) were injected into the limb muscles of each animal (n = 6 per group). Bioluminescence measurement to assess the viability of luciferase positive cells showed significant proliferation of MSCs on day four compared to fibroblasts (p = 0.001). Three weeks after cell delivery, the capillary to muscle fiber ratio of ischemic areas was analyzed. In the MSC group, vessel density was significantly higher than in the fibroblast or control group (0.5 ± 0.08 and 0.3 ± 0.03). Under hypoxia, MSCs produced more VEGF compared to normal conditions and MSC transplantation into murine ischemic limbs led to an increase in vessel density, although MSC survival was limited. This study suggests that MSC transplantation may be an effective and clinically relevant tool in the therapy of occlusive arterial diseases.

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Prof. Sonja Schrepfer, MD, PhD

Cardiothoracic Surgery
Stanford University School of Medicine

300 Pasteur Drive, CRVC

Stanford, CA 94305-5407

United States

Email: schrepfer@stanford.edu

Prof. Sonja Schrepfer, MD, PhD

Cardiovascular Surgery
Campus Foschung, Transplant and Stem Cell, Immunobiology Lab.
University Heart Center Hamburg

Martinistr. 52

24206 Hamburg

Germany

Phone: + 49 40741059982

Fax: + 49 40741059663

Email: schrepfer@stanford.edu