Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy

Jin Ok Jeong, Mee Ohk Kim, Hyongbum Kim, Min Young Lee, Sung Whan Kim, Masaaki Ii, Jung Uek Lee, Jiyoon Lee, Yong Jin Choi, Hyun Jai Cho, Namho Lee, Marcy Silver, Andrea Wecker, Dong Wook Kim, Young sup Yoon

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)699-708
Number of pages10
JournalCirculation
Volume119
Issue number5
DOIs
Publication statusPublished - 2009 Feb 10

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Diabetic Neuropathies
Bone Marrow
Vasa Nervorum
Sciatic Nerve
Endothelial Progenitor Cells
Endothelial Cells
Blood Flow Velocity
Angiogenesis Inducing Agents
Schwann Cells
Neural Conduction
Cell Transplantation
Nerve Growth Factors
Therapeutic Uses
Streptozocin
Conditioned Culture Medium
Peripheral Nerves
Intercellular Signaling Peptides and Proteins
Extremities
Transplantation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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, Young sup. / Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. In: Circulation. 2009 ; Vol. 119, No. 5. pp. 699-708.
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abstract = "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.",
author = "Jeong, {Jin Ok} and Kim, {Mee Ohk} and Hyongbum Kim and Lee, {Min Young} and Kim, {Sung Whan} and Masaaki Ii and Lee, {Jung Uek} and Jiyoon Lee and Choi, {Yong Jin} and Cho, {Hyun Jai} and Namho Lee and Marcy Silver and Andrea Wecker and Kim, {Dong Wook} and Yoon, {Young sup}",
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Jeong, JO, Kim, MO, Kim, H, Lee, MY, Kim, SW, Ii, M, Lee, JU, Lee, J, Choi, YJ, Cho, HJ, Lee, N, Silver, M, Wecker, A, Kim, DW & Yoon, YS 2009, 'Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy', Circulation, vol. 119, no. 5, pp. 699-708. https://doi.org/10.1161/CIRCULATIONAHA.108.789297

Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. / 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, Young sup.

In: Circulation, Vol. 119, No. 5, 10.02.2009, p. 699-708.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy

AU - Jeong, Jin Ok

AU - Kim, Mee Ohk

AU - Kim, Hyongbum

AU - Lee, Min Young

AU - Kim, Sung Whan

AU - Ii, Masaaki

AU - Lee, Jung Uek

AU - Lee, Jiyoon

AU - Choi, Yong Jin

AU - Cho, Hyun Jai

AU - Lee, Namho

AU - Silver, Marcy

AU - Wecker, Andrea

AU - Kim, Dong Wook

AU - Yoon, Young sup

PY - 2009/2/10

Y1 - 2009/2/10

N2 - 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.

AB - 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.

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