Effect of mesenchymal stem cells on movement and urination of rats with spinal cord injury

Abstract

Cell therapy has frequently been reported as a possible treatment for spinal trauma in humans and animals; however, without pharmacologically curative action on damage from the primary lesion. In this study, we evaluated the effect of administering human adipose-derived stem cells (hADSC) in rats after spinal cord injury. The hADSC were used between the third and fifth passages and a proportion of cells were transduced for screening in vivo after transplantation. Spinal cord injury was induced with a Fogarty catheter no. 3 inserted into the epidural space with a cuff located at T8 and filled with 80-μL saline for 5 min. The control group A (n = 12) received culture medium (50 μL) and group B (n = 12) received hADSC (1.2 × 10 6 ) at 7 and 14 days post-injury, in the tail vein. Emptying of the bladder by massage was performed daily for 3 months. Evaluation of functional motor activity was performed daily until 3 months post-injury using the Basso-Beattie-Bresnahan scale. Subsequently, the animals were euthanized and histological analysis of the urinary bladder and spinal cord was performed. Bioluminescence analysis revealed hADSC at the application site and lungs. There was improvement of urinary bladder function in 83.3% animals in group B and 16.66% animals in group A. The analysis of functional motor activity and histology of the spinal cord and urinary bladder demonstrated no significant difference between groups A and B. The results indicate that transplanted hADSC improved urinary function via a telecrine mechanism, namely action at a distance. Key words: Spinal cord injury, paraplegia, urinary incontinence, cell therapy, bioluminescence ResumoA terapia celular tem sido reportada como possibilidade de tratamento para os traumas medulares, frequentes em pessoas e em animais, e que não apresentam cura farmacológica para danos advindos da lesão primária. Foram avaliados os efeitos da aplicação de células-tronco derivadas do tecido adiposo humano (hADSC) em ratos Wistar após lesão medular. As hADSC foram cultivadas, utilizadas entre a terceira e quinta passagens e parte delas foi transduzida para o rastreamento in vivo após o transplante. A lesão medular foi realizada com cateter de Fogarty nº. 3, introduzido no espaço epidural, com cuff localizado em T8 e preenchido com 80 μL de solução salina, por 5 minutos. Os animais do grupo controle (A, n=12) receberam aplicações de meio de cultura (50 μL) e o grupo B (n=12) recebeu duas aplicações de hADSC (1,2 x 10 6 ), sete e 14 dias pós-lesão, ambas na veia da cauda. O esvaziamento vesical, por massagem, foi efetuado diariamente, durante três meses. As avaliações motoras foram repetidas, diariamente, até três meses pós-lesão, utilizando a escala Basso-Beattie-Bresneham. Após este período os animais foram submetidos à eutanásia e foram realizadas análises histológicas de bexiga urinária e medula espinhal. As análises de bioluminescência revelaram hADSC no local da aplicação e nos pulmões. Houve melhora da função da bexiga urinária em 83,3% dos animais do grupo B...

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial

“…Motor vehicle accidents (motorcycle, all-terrain vehicle, or automobile) comprised 50% of the SCI etiology (n = 5), followed by fall-related injuries (n = 3), pedestrian-car accidents (n = 1), and surfing accidents (n = 1). The average duration between injury and AD-MSC injection was 11 months (range of [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. At the time of injection, five patients were classified as AIS grade A, two as AIS B, and three as AIS C. Patient 9 was injected at 22 months post-injury due to failure of adipose tissue expansion.…”

“…The use of AD-MSC has been thoroughly investigated in traumatic and degenerative diseases [7][8][9][10][11] . Preclinical trials in SCI animal models have found evidence that AD-MSCs can regulate the inflammatory response and promote a regenerative environment, correlating with promising clinical outcomes [12][13][14][15] .…”

Efficacy of adipose tissue-derived stem cells in locomotion recovery after spinal cord injury: a systematic review and meta-analysis on animal studies

“…The search came up with 588 non-duplicate results. After initial screening and studying full texts of the articles, 18 articles were included in the current meta-analysis [ 13 – 16 , 22 – 35 ] (Fig. 1 ).…”

“…One of the articles presented two different sets of data [ 14 ], so the results from 19 unique experiments were analyzed. Two studies were in Chinese [ 33 , 34 ], and 16 articles were in English [ 13 – 16 , 22 – 32 , 35 ]. Experiments were performed on 567 rats (275 rats in the SCI group and 292 rats in ADSCs-treated groups).…”

Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury

“…A great number of studies have been performed with stem cells from different sources using animal models of spinal cord injury, and even therapeutic attempts on humans, presenting promising results [5][6][7] . However, there are some difficulties to perform a direct comparison of such results, due to the large variability of characterization grade of the transplanted cells, different animal models, and the time fluctuation between injury event and its treatment Commonly, dogs present clinical injuries of the thoracic and lumbar spinal medulla mainly due to herniation or protrusion of the intervertebral discs 9 .…”