Ann Thorac Surg 2006;81:1736-1737
© 2006 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Olivier Dormond, MD, PhD,
Joren C. Madsen, MD, DPhil
Bulfinch 119, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114
(Email: olivier.dormand{at}tbrc.mgh.harvard.edu; madsen{at}helix.mgh.harvard.edu).
The use of endothelial progenitor cells (EPCs) in the treatment of ischemic disease is a promising new approach. Multiple reports in animal models have shown that the injection of ex vivo expanded EPCs or stem cell progenitors can home sites of ischemia and participate to vasculogenesis [1]. Moreover, initial trials in human demonstrated that the use of ex vivo expanded progenitor cells is safe and improves blood supply to ischemic tissue. Injection of EPCs in patients with acute myocardial infarction improved left ventricular function and coronary flow reserve [2]. Autologous implantation of bone marrow derived mononuclear cells had therapeutic benefits in patients with ischemic limbs [3]. Although the use of ex vivo expanded EPCs has been successful, inherent risks to this technique exists, like transmission of infectious diseases.
To minimize these risks, Atluri and colleagues [4] propose another approach. They use granulocyte-macrophage colony-stimulating factor (GM-CSF) to mobilize endogenous EPCs from the animal's own bone marrow and induce them to traffic to ischemic tissue by injecting stromal cell-derived factor-1 (SDF-1) at the ischemic site. They show that this technique increases perfusion of the ischemic myocardial border zone and thus enhances myocardial viability.
Although an ingenious strategy, the use of this approach in the clinic may be problematic. It is well established that patients with coronary heart disease (CHD) have reduced circulating endothelial progenitor cells with reduced functional capacity. This seems to be due to an impaired ability of EPCs from patients with CAD to be mobilized from the bone marrow. This is supported by the fact that the number of EPCs in the bone marrow of healthy volunteers is identical to the number of EPCs in the bone marrow of patients with CHD [5]. Also consistent with this finding is the fact that patients with CHD have reduced levels of endothelium-derived nitric oxide that result in defective EPC mobilization from bone marrow [6]. It is thus conceivable that the use of GM-CSF in patients with coronary heart disease will not be sufficient to induce the mobilization of EPCs. Moreover, progenitor cells from patients with chronic ischemic heart disease have a reduced migratory response to SDF-1 in vitro so that SDF-1 may not be as effective in patients with chronic ischemic heart disease [5]. The good news is the use of GM-CSF in patients with coronary artery disease has been reported to promote collateral growth [7].
Even though the translation of this GM-CSF and SDF-1 protocol to the clinic may not be straightforward (as it never is), the basic neovasculogenic strategy proposed by the authors is important and warrants further testing in large animals.
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- Britten MB, Abolmaali ND, Assmus B, et al. Infarct Remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI) Circulation 2003;108:2212-2218.[Abstract/Free Full Text]
- Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cellsa pilot study and a randomised controlled trial. Lancet 2002;360:427-435.[Medline]
- Atluri P, Liao GP, Panlilio CM, et al. Neovasculogenic therapy to augment and preserve viability in ischemic cardiomyopathy Ann Thorac Surg 2006;81:1728-1737.[Abstract/Free Full Text]
- Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease Circulation 2004;109:1615-1622.[Abstract/Free Full Text]
- Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells Nat Med 2003;9:1370-1376.[Medline]
- Seiler C, Pohl T, Wustmann K, et al. Promotion of collateral growth by granulocyte- macrophage colony-stimulating factor in patients with coronary artery disease Circulation 2001;104:2012-2017.[Abstract/Free Full Text]
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