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2016 ; 25
(2
): 313-26
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gab.com Text
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Bone Marrow-Derived Mesenchymal Stem Cells Improve Diabetic Neuropathy by Direct
Modulation of Both Angiogenesis and Myelination in Peripheral Nerves
#MMPMID25975801
Han JW
; Choi D
; Lee MY
; Huh YH
; Yoon YS
Cell Transplant
2016[]; 25
(2
): 313-26
PMID25975801
show ga
Recent evidence has suggested that diabetic neuropathy (DN) is
pathophysiologically related to both impaired angiogenesis and a deficiency of
neurotrophic factors in the nerves. It is widely known that vascular and neural
growths are intimately associated. Mesenchymal stem cells (MSCs) promote
angiogenesis in ischemic diseases and have neuroprotective effects, particularly
on Schwann cells. Accordingly, we investigated whether DN could be improved by
local transplantation of MSCs by augmenting angiogenesis and neural regeneration
such as remyelination. In sciatic nerves of streptozotocin (STZ)-induced diabetic
rats, motor and sensory nerve conduction velocities (NCVs) and capillary density
were reduced, and axonal atrophy and demyelination were observed. After injection
of bone marrow-derived MSCs (BM-MSCs) into hindlimb muscles, NCVs were restored
to near-normal levels. Histological examination demonstrated that injected MSCs
were preferentially and durably engrafted in the sciatic nerves, and a portion of
the engrafted MSCs were distinctively localized close to vasa nervora of sciatic
nerves. Furthermore, vasa nervora increased in density, and the ultrastructure of
myelinated fibers in nerves was observed to be restored. Real-time RT-PCR
experiments showed that gene expression of multiple factors involved in
angiogenesis, neural function, and myelination were increased in the MSC-injected
nerves. These findings suggest that MSC transplantation improved DN through
direct peripheral nerve angiogenesis, neurotrophic effects, and restoration of
myelination.