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Diabetes Care 29:478-479, 2006
DOI: 10.2337/diacare.29.02.06.dc05-1770
© 2006 by the American Diabetes Association
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Diabetes Care 29:478-479, 2006
© 2006 by the American Diabetes Association, Inc.

Letters: Comments and Responses
Letters: Comments and Responses

Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes

Response to Huang et al.

Gian Paolo Fadini, MD and Angelo Avogaro, MD, PHD

Department of Clinical and Experimental Medicine, Metabolic Division, University of Padova Medical School, Padova, Italy

Address correspondence to Gian Paolo Fadini, MD, Dipartimento di Medicina Clinica e Sperimentale, Divisione di Malattie del Metabolismo, Policlinico Universitario, Via Giustiniani, 2, 35100 Padova, Italy. E-mail: gianpaolofadini{at}hotmail.com

Huang et al. (1), in their small seminal clinical trial of cellular therapy for critical limb ischemia in diabetic patients, did not include presence of diabetic retinopathy among their exclusion criteria. It is known that individuals with diabetes are subjected to poor blood vessel growth in ischemic hearts and limbs and increased angiogenesis in retinal complications. This so-called "diabetic paradox" has been attributed to the differential regulation of angiogenic factors in the retina versus the systemic circulation (2). While decreased levels of endothelial progenitor cells are seen in diabetic patients with peripheral arterial disease (3), a role for endothelial progenitor cells in the development of proliferative diabetic retinopathy (PDR) also has been demonstrated (4). Possible harmful side effects of progenitor cell transplantation may include pathologic neoangiogenesis favoring the development or progression of cancer or PDR (5). Moreover, although data on blood cells are not presented, the increased blood viscosity due to the leukemoid response to granulocyte colony–stimulating factor may favor retinal vessel occlusion. Therefore, it was desirable that patients were screened for PDR before and after cell transplantation, in order to identify or exclude such an undesirable effect.

Finally, the achievement of a better metabolic control in the transplant group than in the control group is not unexpected and can be explained without postulating ß-cell regeneration, since wound healing per se and reduced inflammation may have improved insulin sensitivity. The authors correctly cite the hypothesis that circulating progenitor cells may have a role in rescue of pancreatic endocrine function (6), but this has not been demonstrated thus far. Transplanted cells are recruited in the pancreas of streptozotocin-induced diabetic animals, but neither sign of endocrine transdifferentiation nor improvement in blood glucose metabolism have been shown (7). Moreover, this claimed mechanism would clearly interest only those forms of diabetes due to primitive ß-cell failure, while only 40% of the study patients had type 1 diabetes.

References

  1. Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC: Autologous transplantation of granulocyte colony–stimulating factor–mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 28:2155–2160, 2005[Abstract/Free Full Text]
  2. Duh E, Aiello LP: Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. Diabetes 48:1899–1906, 1999[Abstract]
  3. Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, Avogaro A: Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 45:1449–1457, 2005[Abstract/Free Full Text]
  4. Lee IG, Chae SL, Kim JC: Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy. Eye 2005 [Epub ahead of print]
  5. Ishikawa M, Asahara T: Endothelial progenitor cell culture for vascular regeneration. Stem Cells Dev 13:344–349, 2004[Medline]
  6. Suzuki A, Nakauchi H, Taniguchi H: Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53:2143–2152, 2004[Abstract/Free Full Text]
  7. Mathews V, Hanson PT, Ford E, Fujita J, Polonsky KS, Graubert TA: Recruitment of bone marrow–derived endothelial cells to sites of pancreatic ß-cell injury. Diabetes 53:91–98, 2004[Abstract/Free Full Text]

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G. P. Fadini, S. Sartore, I. Baesso, M. Lenzi, C. Agostini, A. Tiengo, and A. Avogaro
Endothelial progenitor cells and the diabetic paradox.
Diabetes Care, March 1, 2006; 29(3): 714 - 716.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
B. Zhou, P. Huang, and Z. C. Han
Autologous Transplantation of Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes: Response to Fadini and Avogaro
Diabetes Care, February 1, 2006; 29(2): 479 - 480.
[Full Text] [PDF]

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