CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Ioakim Spyridopoulos, MD*,
Christine K. Kissel, MD,
Stefanie Dimmeler, PhD and
Andreas M. Zeiher, MD
* Department of Cardiology and Molecular Cardiology, Johann Wolfgang Goethe University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany (Email: spyridopoulos{at}em.uni-frankfurt.de).
We greatly appreciate the comment by Dr. Oeseburg and colleagues hinting at a potential relationship between mean telomere length (mTL) and functional exhaustion of hematopoietic progenitor cells. Accordingly, we have reanalyzed data from 43 patients with congestive heart failure (37 with ischemic cardiomyopathy and 6 with nonischemic cardiomyopathy) from our bone marrow-mononuclear cell (BM-MNC) study population (1), where we had simultaneously determined mTL of peripheral blood cells. The mean age of this subpopulation was 62 ± 9 years, mean ejection fraction was 28 ± 8%, and mean N-terminal prohormone brain natriuretic peptide serum levels were 1,850 ± 2,727 ng/ml. We have chosen mTL from peripheral blood granulocytes, which best reflects mTL of bone marrow-residing CD34+ stem cells (I. Spyridopoulos et al., personal communication, September 2007) (2) and compared it with the colony-forming activity of BM-MNCs.
A significant correlation was found, as illustrated in Figure 1
(r = 0.53, p < 0.001), between mTL of granulocytes and colony-forming capacity of BM-MNCs. Although age is the most important determinant of telomere length, age did not correlate with colony-forming activity in the present study cohort. In addition, mTL of lymphocytes also demonstrated a significant correlation with colony-forming capacity of BM-MNCs (r = 0.447, p = 0.003). These data indeed suggest an association between reduced "stem or progenitor cell" mTL and impaired hematopoietic functionality of BM-MNCs.
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Figure 1 Telomere Length and Bone Marrow Function
Correlation of mean telomere length (mTL) of the granulocytes with colony-forming capacity of bone marrow-derived mononuclear cells in patients with heart failure. Dotted line indicates the linear regression curve.
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Because of the limited sample size of our study, however, we could not differentiate between ischemic and nonischemic etiology of heart failure. We would also like to point out that telomere length from granulocytes might not reflect mTL from the colony-forming cells, which are just a small clonal subpopulation with high proliferative potential.
In vivo data from patients after bone marrow transplantation show that hematopoietic stem cells lose telomere length by further division, leading to reduced proliferative potential (3). Experiments in telomerase-deficient mice demonstrate that telomere shortening leads to impaired mobilization of epidermal stem cells and suppression of their clonogenic capacity (4). Our results would indeed favor the hypothesis that telomere length has implications on the functional capacity of hematopoietic progenitor cells in patients with heart failure.
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References
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1. Kissel CK, Lehmann R, Assmus B, et al. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure J Am Coll Cardiol 2007;49:2341-2349.[Abstract/Free Full Text]2. Sakoff JA, De Waal E, Garg MB, et al. Telomere length in haemopoietic stem cells can be determined from that of mononuclear blood cells or whole blood Leuk Lymphoma 2002;43:2017-2020.[CrossRef][Web of Science][Medline] 3. Notaro R, Cimmino A, Tabarini D, et al. In vivo telomere dynamics of human hematopoietic stem cells Proc Natl Acad Sci U S A 1997;94:13782-13785.[Abstract/Free Full Text] 4. Flores I, Cayuela ML, Blasco MA. Effects of telomerase and telomere length on epidermal stem cell behavior Science 2005;309:1253-1256.[Abstract/Free Full Text]
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