Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood

Mesenchymal stem cells (MSCs) represent a promising means to promote tissue regeneration. However, the heterogeneity of MSCs impedes their use for regenerative medicine. Further investigation of this phenotype is required to develop cell therapies with improved clinical efficacy. Here, a small-sized population of human umbilical cord blood-derived MSCs (UCB-MSCs) was isolated using a filter and centrifuge system to analyze its stem cell characteristics. Consequently, this population showed higher cell growth and lower senescence. Additionally, it exhibited diverse stem cell properties including differentiation, stemness, and adhesion, as compared to those of the population before isolation. Using cell surface protein array or sorting analysis, both EGFR and CD49f were identified as markers associated with the small-sized population. Accordingly, suppression of these surface proteins abolished the superior characteristics of this population. Moreover, compared to that with large or nonisolated populations, the small-sized population showed greater therapeutic efficacy by promoting the engraftment potential of infused cells and reducing lung damage in an emphysema mouse model. Therefore, the isolation of this small-sized population of UCB-MSCs could be a simple and effective way to enhance the efficacy of cell therapy.

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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

Neural Plasticity ◽

10.1155/2017/9857918 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Y. O. Mukhamedshina ◽

Z. E. Gilazieva ◽

S. S. Arkhipova ◽

L. R. Galieva ◽

E. E. Garanina ◽

...

Keyword(s):

Spinal Cord ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Mononuclear Cells ◽

Genetically Modified ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Blood Mononuclear Cells ◽

Cord Blood Mononuclear Cells

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 inH(latency period, LP) andM(Amax)waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement inAmaxofMwave and LP of both theMandHwaves. The ratio betweenAmaxof theHandMwaves (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.

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