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Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.

Abstract In this study, we examined the efficacy of human umbilical cord blood mononuclear cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using adenoviral vectors, on posttraumatic regeneration after transplantation into the site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by transplantation of nontransduced hUCB-MCs, we observed an improvement in H (latency period, LP) and M(Amax) waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M wave and LP of both the M and H waves. The ratio between Amax of the H and M waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs. Spared tissue and myelinated fibers were increased at day 30 after SCI and transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF and GNDF genes significantly increased the number of spared myelinated fibers (22-fold, P > 0.01) in the main corticospinal tract compared to the nontransduced ones. HNA(+) cells with the morphology of phagocytes and microglia-like cells were found as compact clusters or cell bridges within the traumatic cavities that were lined by GFAP(+) host astrocytes. Our results show that hUCB-MCs transplanted into the site of SCI improved regeneration and that hUCB-MCs genetically modified with the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title neural plasticity
Publication Year Start




PMID- 28421147
OWN - NLM
STAT- MEDLINE
DA  - 20170419
DCOM- 20170428
LR  - 20170428
IS  - 1687-5443 (Electronic)
IS  - 1687-5443 (Linking)
VI  - 2017
DP  - 2017
TI  - Electrophysiological, Morphological, and Ultrastructural Features of the Injured 
      Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood
      Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.
PG  - 9857918
LID - 10.1155/2017/9857918 [doi]
AB  - In this study, we examined the efficacy of human umbilical cord blood mononuclear
      cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using
      adenoviral vectors, on posttraumatic regeneration after transplantation into the 
      site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by
      transplantation of nontransduced hUCB-MCs, we observed an improvement in H
      (latency period, LP) and M(Amax) waves, compared to the group without therapy
      after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M 
      wave and LP of both the M and H waves. The ratio between Amax of the H and M
      waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of
      genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs.
      Spared tissue and myelinated fibers were increased at day 30 after SCI and
      transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the
      lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF 
      and GNDF genes significantly increased the number of spared myelinated fibers
      (22-fold, P > 0.01) in the main corticospinal tract compared to the nontransduced
      ones. HNA+ cells with the morphology of phagocytes and microglia-like cells were 
      found as compact clusters or cell bridges within the traumatic cavities that were
      lined by GFAP+ host astrocytes. Our results show that hUCB-MCs transplanted into 
      the site of SCI improved regeneration and that hUCB-MCs genetically modified with
      the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.
FAU - Mukhamedshina, Y O
AU  - Mukhamedshina YO
AUID- ORCID: 0000-0002-9435-340X
AD  - Kazan Federal University, Kazan, Russia.
AD  - Kazan State Medical University, Kazan, Russia.
FAU - Gilazieva, Z E
AU  - Gilazieva ZE
AD  - Kazan Federal University, Kazan, Russia.
FAU - Arkhipova, S S
AU  - Arkhipova SS
AD  - Kazan Federal University, Kazan, Russia.
FAU - Galieva, L R
AU  - Galieva LR
AD  - Kazan Federal University, Kazan, Russia.
FAU - Garanina, E E
AU  - Garanina EE
AD  - Kazan Federal University, Kazan, Russia.
FAU - Shulman, A A
AU  - Shulman AA
AD  - Republic Clinical Hospital, Kazan, Russia.
FAU - Yafarova, G G
AU  - Yafarova GG
AD  - Kazan Federal University, Kazan, Russia.
AD  - Republic Clinical Hospital, Kazan, Russia.
FAU - Chelyshev, Y A
AU  - Chelyshev YA
AD  - Kazan Federal University, Kazan, Russia.
AD  - Kazan State Medical University, Kazan, Russia.
FAU - Shamsutdinova, N V
AU  - Shamsutdinova NV
AD  - Kazan State Academy of Veterinary Medicine, Kazan, Russia.
FAU - Rizvanov, A A
AU  - Rizvanov AA
AUID- ORCID: 0000-0002-9427-5739
AD  - Kazan Federal University, Kazan, Russia.
LA  - eng
PT  - Journal Article
DEP - 20170321
PL  - United States
TA  - Neural Plast
JT  - Neural plasticity
JID - 100883417
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Adenoviridae
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Transplantation/*methods
MH  - Female
MH  - Fetal Blood/cytology
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors
MH  - Glial Cell Line-Derived Neurotrophic Factor/*genetics
MH  - Humans
MH  - Leukocytes, Mononuclear/pathology/physiology/*transplantation/ultrastructure
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Spinal Cord Injuries/pathology/physiopathology/*therapy
MH  - Transplantation, Heterologous
MH  - Vascular Endothelial Growth Factor A/*genetics
PMC - PMC5379091
COI - The authors declare that there is no conflict of interests regarding the
      publication of this paper.
EDAT- 2017/04/20 06:00
MHDA- 2017/04/30 06:00
CRDT- 2017/04/20 06:00
PHST- 2016/09/19 [received]
PHST- 2017/01/24 [accepted]
AID - 10.1155/2017/9857918 [doi]
PST - ppublish
SO  - Neural Plast. 2017;2017:9857918. doi: 10.1155/2017/9857918. Epub 2017 Mar 21.

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