Synergistic angiogenic effect of codelivering fibroblast growth factor 2 and granulocyte-colony stimulating factor from fibrin scaffolds and bone marrow transplantation in critical limb ischemia

Hans Layman, Amir A. Rahnemai-Azar, Si M. Pham, Gavriil Tsechpenakis, Fotios M. Andreopoulos

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Increasing evidence suggests that therapeutic angiogenesis strategies utilizing cytokines and stem cells are necessary to treat traumatic vascular events such as critical limb ischemia and peripheral artery disease. In this study, basic fibroblast growth factor 2 (FGF-2) and granulocyte-colony stimulating factor (G-CSF) were immobilized in fibrin matrices and codelivered in combination with unfractionated bone marrow cells. Hindlimb ischemia was induced on young (6-7 weeks) Balb/C mice, and fibrin gels containing 100ng/mL of FGF-2 and G-CSF were implanted adjacent to the ligation points. In addition, 1×106 bone marrow (BM) cells were injected into five locations in the ischemic muscle immediately after ligation and artery excision. Hindlimb reperfusion was determined by Laser Doppler Perfusion Imaging and immunohistochemistry for CD31+ and smooth muscle actin-positive cells at 2, 4, and 8 weeks postsurgery to identify capillary formation and maturation. A fluorescent vessel painting technique was also utilized to determine the extent of angiogenesis and arteriogenesis in the hindlimb at 8 weeks postsurgery. The codelivery of FGF-2 and G-CSF in combination with BM cells led to enhanced therapeutic recovery in critical limb ischemia Balb/C mice after 8 weeks of treatment with 87.2% blood flow recovery and a significant increase (p<0.05) in capillary formation in comparison to growth factor delivery or BM cell administration alone.

Original languageEnglish (US)
Pages (from-to)243-254
Number of pages12
JournalTissue Engineering - Part A
Volume17
Issue number1-2
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Synergistic angiogenic effect of codelivering fibroblast growth factor 2 and granulocyte-colony stimulating factor from fibrin scaffolds and bone marrow transplantation in critical limb ischemia'. Together they form a unique fingerprint.

Cite this