Bone Marrow Mononuclear Cells Have Neurovascular Tropism and Improve Diabetic Neuropathy

• Type of Material: Article
• Authors: Hyongbum Kim, Emory University; Jong-seon Park, Tufts University; Yong Jin Choi, Emory University; Mee-Ohk Kim, Emory University; Yang Hoon Huh, Boston Biomedical Research Institute; Sung-Whan Kim, Emory University; Ji Woong Han, Emory University; JiYoon Lee, Emory University; Sinae Kim, Emory University; Mackenzie A. Houge, Emory University; Masaaki Ii, Tufts University; Young-sup Yoon, Emory University
• Language: English
• Date: 2009-07
• Publisher: AlphaMed Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 AlphaMed Press
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/stem.87/abstract
• Title of Journal or Parent Work: STEM CELLS
• ISSN: 1066-5099
• Volume: 27
• Issue: 7
• Start Page: 1686
• End Page: 1696
• Grant/Funding Information: This work was supported in part by NIH grants (HL079137, HL084471), a Juvenile Diabetic Research Foundation Innovation Grant (5–2007-951), and a grant (SC4300) from the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea.
• Keywords: Angiogenic factors; Angiogenesis; Diabetic neuropathy; Neurotrophic factors; Bone marrow mononuclear cells; Diabetes
• Research Categories: Biology, Neuroscience

Abstract

Bone marrow-derived mononuclear cells (BMNCs) have been shown to effectively treat ischemic cardiovascular diseases. Because diabetic neuropathy (DN) is causally associated with impaired angiogenesis and deficiency of angiogenic and neurotrophic factors in the nerves, we investigated whether DN can be ameliorated by local injection of BMNCs. Severe peripheral neuropathy, characterized by a significant decrease in the motor and sensory nerve conduction velocities (NCVs), developed 12 weeks after the induction of diabetes with streptozotocin in rats. The injection of BMNCs restored motor and sensory NCVs to normal levels and significantly improved vascular density and blood flow in diabetic nerves over 4 weeks. Fluorescent microscopic observation revealed that DiI-labeled BMNCs preferentially engrafted in sciatic nerves. Whole-mount fluorescent imaging and confocal microscopic evaluation demonstrated that many of the BMNCs localized following the course of the vasa nervorum in close proximity to blood vessels without incorporation into vasa nervorum as endothelial cells at a detectable level. Real-time reverse transcription-polymerase chain reaction analysis showed that the levels of angiogenic and neurotrophic factors were significantly increased in the nerves by BMNC injection. Local transplantation of BMNCs improved experimental DN by augmenting angiogenesis and increasing angiogenic and neurotrophic factors in peripheral nerves. These findings suggest that BMNC transplantation may represent a novel therapeutic option for treating DN.