title: Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy.
abstract: Relief from painful diabetic neuropathy is an important clinical issue. We have previously shown that the transplantation of cultured endothelial progenitor cells or mesenchymal stem cells ameliorated diabetic neuropathy in rats. In this study, we investigated whether transplantation of freshly isolated bone marrow-derived mononuclear cells (BM-MNCs) alleviates neuropathic pain in the early stage of streptozotocin-induced diabetic rats. Two weeks after STZ injection, BM-MNCs or vehicle saline were injected into the unilateral hind limb muscles. Mechanical hyperalgesia and cold allodynia in SD rats were measured as the number of foot withdrawals to von Frey hair stimulation and acetone application, respectively. Two weeks after the BM-MNC transplantation, sciatic motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), sciatic nerve blood flow (SNBF), mRNA expressions and histology were assessed. The BM-MNC transplantation significantly ameliorated mechanical hyperalgesia and cold allodynia in the BM-MNC-injected side. Furthermore, the slowed MNCV/SNCV and decreased SNBF in diabetic rats were improved in the BM-MNC-injected side. BM-MNC transplantation improved the decreased mRNA expression of NT-3 and number of microvessels in the hind limb muscles. There was no distinct effect of BM-MNC transplantation on the intraepidermal nerve fiber density. These results suggest that autologous transplantation of BM-MNCs could be a novel strategy for the treatment of painful diabetic neuropathy.
authors: Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan. narusek@dpc.agu.ac.jp
authors: Keiko
authors: K
authors: Naruse
authors: Jun
authors: J
authors: Sato
authors: Megumi
authors: M
authors: Funakubo
authors: Masaki
authors: M
authors: Hata
authors: Nobuhisa
authors: N
authors: Nakamura
authors: Yasuko
authors: Y
authors: Kobayashi
authors: Hideki
authors: H
authors: Kamiya
authors: Taiga
authors: T
authors: Shibata
authors: Masaki
authors: M
authors: Kondo
authors: Tatsuhito
authors: T
authors: Himeno
authors: Tatsuaki
authors: T
authors: Matsubara
authors: Yutaka
authors: Y
authors: Oiso
authors: Jiro
authors: J
authors: Nakamura
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D016026:Bone Marrow Transplantation; D002196:Capillaries / Q000503:physiopathology; D003080:Cold Temperature; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology / Q000601:surgery; D003929:Diabetic Neuropathies / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*; D015870:Gene Expression; D006930:Hyperalgesia / Q000503:physiopathology / Q000601:surgery*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D009412:Nerve Fibers / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000098:blood supply / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D009414:Nerve Growth Factors