Therapeutic Neovascularization Using Cord Blood–Derived Endothelial Progenitor Cells for Diabetic Neuropathy

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 6; pp. 1823 - 1828
• Main Authors: NARUSE, Keiko, HAMADA, Yoji, OISO, Yutaka, NAKAMURA, Jiro, NAKASHIMA, Eitaro, KATO, Koichi, MIZUBAYASHI, Ryuichi, KAMIYA, Hideki, YUZAWA, Yukio, MATSUO, Seiichi, MUROHARA, Toyoaki, MATSUBARA, Tatsuaki
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2005
• Subjects: Angiogenesis; Animals; Anticoagulants; Biological and medical sciences; Bone marrow; Care and treatment; Cell cycle; Cloning; Complications and side effects; Cord Blood Stem Cell Transplantation; Diabetes; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Diabetic neuropathies; Diabetic Neuropathies - therapy; Diabetic neuropathy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - cytology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fetal blood; Flow cytometry; Hindlimb; Humans; Ischemia; Male; Medical sciences; Metabolism; Muscle, Skeletal - physiology; Neovascularization; Neovascularization, Physiologic - physiology; Neural Conduction - physiology; Peripheral nerve diseases; Peripheral nervous system diseases; Rats; Rats, Inbred F344; Rats, Nude; Sciatic Nerve - blood supply; Sciatic Nerve - physiology; Umbilical cord; Velocity; Japan; Endocrinopathy; Nervous system diseases; Endothelial cell; Diabetes mellitus; Precursor cell; Neuropathy; Neovascularization
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.6.1823

Therapeutic Neovascularization Using Cord Blood–Derived Endothelial Progenitor Cells for Diabetic Neuropathy Keiko Naruse 1 , Yoji Hamada 2 , Eitaro Nakashima 2 , Koichi Kato 3 , Ryuichi Mizubayashi 2 , Hideki Kamiya 2 , Yukio Yuzawa 4 , Seiichi Matsuo 4 , Toyoaki Murohara 5 , Tatsuaki Matsubara 1 , Yutaka Oiso 2 and Jiro Nakamura 2 1 Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan 2 Division of Metabolic Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan 3 Division of Endocrinology, Metabolism and Diabetology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Aichi, Japan 4 Division of Clinical Immunology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan 5 Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan Address correspondence and reprint requests to Keiko Naruse, MD, PhD, Department of Internal Medicine, Aichi-Gakuin University, School of Dentistry 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan. E-mail: narusek{at}dpc.aichi-gakuin.ac.jp Abstract Diabetic neuropathy is based on the impairment of nerve blood flow and the metabolic disorder. Although the vasodilating agents and anticoagulants improve nerve function and symptoms in diabetic neuropathy, more effective treatments are needed. Because endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood, many studies have shown that transplantation of EPCs improves circulation to ischemic tissues. In this study, we have demonstrated that therapeutic neovascularization using human umbilical cord blood–derived EPCs reversed diabetic neuropathy. EPCs were isolated and expanded on day 7 of culture from cord blood mononuclear cells. Unilateral intramuscular injection of EPCs into hindlimb skeletal muscles significantly ameliorated impaired sciatic motor nerve conduction velocity and sciatic nerve blood flow in the EPC-injected side of streptozotocin-induced diabetic nude rats compared with the saline-injected side of diabetic nude rats. Histological study revealed an increased number of microvessels in hindlimb skeletal muscles in the EPC-injected side of diabetic rats. These findings suggest that transplantation of EPCs from cord blood may be a useful treatment for diabetic neuropathy. DiI, 3,3′-dioctadecylindocarbocyanine EPC, endothelial progenitor cell MNC, mononuclear cell MNCV, motor nerve conduction velocity SNBF, sciatic endoneurial nutritive blood flow STZ, streptozotocin VEGF, vascular endothelial growth factor vWF, von Willebrand factor Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted February 21, 2005. Received December 3, 2004. DIABETES