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Bone Marrow Mononuclear Cells Have Neurovascular Tropism and Improve Diabetic Neuropathy
Kim, Hyongbum,Park, Jong-seon,Choi, Yong Jin,Kim, Mee-Ohk,Huh, Yang Hoon,Kim, Sung-Whan,Han, Ji Woong,Lee, JiYoon,Kim, Sinae,Houge, Mackenzie A.,Ii, Masaaki,Yoon, Young-sup Wiley (John WileySons) 2009 Stem Cells Vol.27 No.7
<P>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.</P>
Yang, Jae-Wook,Lee, Soung-Min,Oh, Kyeong-Hee,Park, Sae-Gwang,Choi, Ii-Whan,Seo, Su-Kil SPANDIDOS PUBLICATIONS 2015 MOLECULAR MEDICINE REPORTS Vol.11 No.1
<P>Numerous treatments have been used in the management of corneal chemical burns; however, no optimal treatment for corneal chemical burns currently exists. The present study investigated the effects of topical chondrocyte-derived extracellular matrix (CD-ECM) treatment on corneal wound healing, using an alkali burn mouse model. Topical treatment with CD-ECM was shown to reduce corneal opacity following an alkali burn. A histological examination observed the presence of regenerated epithelial cells and a small number of inflammatory cells in the corneas of CD-ECM-treated mice. The majority of the inflammatory cells present in the corneas of the phosphate-buffered saline (PBS)-treated mice were neutrophils that expressed matrix metalloproteinase (MMP)-9. The amount of neutrophils was significantly reduced in the corneas of the CD-ECM-treated mice. Furthermore, the expression levels of interleukin (IL)-8 were significantly reduced in the CD-ECM treatment group, but not in the mice that received the PBS treatment. The results of the present study indicate that CD-ECM treatment may accelerate wound healing in a model of alkali burn-induced corneal injury. The therapeutic mechanism may be associated with accelerated reepithelialization and reduced recruitment of MMP-9-expressing neutrophils, through inhibiting the production of IL-8.</P>
Jeong, Jin-Ok,Kim, Mee-Ohk,Kim, Hyongbum,Lee, Min-Young,Kim, Sung-Whan,Ii, Masaaki,Lee, Jung-uek,Lee, Jiyoon,Choi, Yong Jin,Cho, Hyun-Jai,Lee, Namho,Silver, Marcy,Wecker, Andrea,Kim, Dong-Wook,Yoon, Y Ovid Technologies Wolters Kluwer -American Heart A 2009 CIRCULATION - Vol.119 No.5
<P>BACKGROUND: Endothelial progenitor cells (EPCs) are known to promote neovascularization in ischemic diseases. Recent evidence suggested that diabetic neuropathy is causally related to impaired angiogenesis and deficient growth factors. Accordingly, we investigated whether diabetic neuropathy could be reversed by local transplantation of EPCs. METHODS AND RESULTS: We found that motor and sensory nerve conduction velocities, blood flow, and capillary density were reduced in sciatic nerves of streptozotocin-induced diabetic mice but recovered to normal levels after hind-limb injection of bone marrow-derived EPCs. Injected EPCs were preferentially and durably engrafted in the sciatic nerves. A portion of engrafted EPCs were uniquely localized in close proximity to vasa nervorum, and a smaller portion of these EPCs were colocalized with endothelial cells. Multiple angiogenic and neurotrophic factors were significantly increased in the EPC-injected nerves. These dual angiogenic and neurotrophic effects of EPCs were confirmed by higher proliferation of Schwann cells and endothelial cells cultured in EPC-conditioned media. CONCLUSIONS: We demonstrate for the first time that bone marrow-derived EPCs could reverse various manifestations of diabetic neuropathy. These therapeutic effects were mediated by direct augmentation of neovascularization in peripheral nerves through long-term and preferential engraftment of EPCs in nerves and particularly vasa nervorum and their paracrine effects. These findings suggest that EPC transplantation could represent an innovative therapeutic option for treating diabetic neuropathy.</P>