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Open AccessArticle

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

1
Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Кazan Federal University, Kazan 420008, Russia
2
Department of Histology, Cytology, and Embryology, Kazan State Medical University, Kazan 420012, Russia
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Republic Clinical Hospital, Kazan 420138, Russia
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Department of Neurology, Kazan State Medical Academy–Branch Campus of the Federal State Budgetary Edicational Institution of Father Professional Education «Russian Medical Academy of Continuous Professional Education», Kazan 420012, Russia
5
Division of Biomedical Science, School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham Biodiscovery Institute, University Park, NG7 2RD Nottingham, UK
6
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA
7
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 811; https://doi.org/10.3390/biom9120811
Received: 30 September 2019 / Revised: 5 November 2019 / Accepted: 26 November 2019 / Published: 1 December 2019
(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)
Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.
Keywords: Keywords spinal cord injury; mesenchymal stem cells; adipose tissue; bone marrow; dental pulp; fibrin matrix; rat; pig Keywords spinal cord injury; mesenchymal stem cells; adipose tissue; bone marrow; dental pulp; fibrin matrix; rat; pig
MDPI and ACS Style

Mukhamedshina, Y.; Shulman, I.; Ogurcov, S.; Kostennikov, A.; Zakirova, E.; Akhmetzyanova, E.; Rogozhin, A.; Masgutova, G.; James, V.; Masgutov, R.; Lavrov, I.; Rizvanov, A. Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models. Biomolecules 2019, 9, 811.

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