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

  1. Keiko Naruse1,
  2. Yoji Hamada2,
  3. Eitaro Nakashima2,
  4. Koichi Kato3,
  5. Ryuichi Mizubayashi2,
  6. Hideki Kamiya2,
  7. Yukio Yuzawa4,
  8. Seiichi Matsuo4,
  9. Toyoaki Murohara5,
  10. Tatsuaki Matsubara1,
  11. Yutaka Oiso2 and
  12. Jiro Nakamura2
  1. 1Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
  2. 2Division of Metabolic Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
  3. 3Division of Endocrinology, Metabolism and Diabetology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Aichi, Japan
  4. 4Division of Clinical Immunology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
  5. 5Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  1. 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}


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.


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    • Accepted February 21, 2005.
    • Received December 3, 2004.
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