Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats.
This study aimed to evaluate the immunomodulatory and neuroprotective effects of allogeneic and cryopreserved mesenchymal stem cells (MSCs) on spinal cord injury. A total of 120 rats were distributed into the following groups: negative control (NC) - without injury, positive control (PC) - with injury without treatment, and group treated with MSC (GMSC) - with injury and treated. Motor function was evaluated by the BBB test at 24, 48, and 72 h and at 8 and 21 postoperative days. Spinal cords were evaluated by histopathology and immunohistochemistry to determine the expression of CD68, NeuN, and GFAP. IL-10, TNF-α, IL-1β, TGF-β, BDNF, GDNF, and VEGF expression was quantified by RT-PCR. The GMSC presented higher scores for motor function at 72 h and 8 and 21 days after injury, lower expression of CD68 at 8 days, and lower expression of GFAP at 21 days compared to the PC. In addition, higher expression of NeuN and lower degeneration of the white matter occurred at 21 days. The GMSC also showed higher expression of IL-10 24 h after injury, GDNF at 48 h and 8 days, and VEGF at 21 days. Moreover, lower expression of TNF-α was observed at 8 and 21 days and TGF-β at 24 h and 21 days. There were no differences in the expression of IL-1β and BDNF between the GMSC and PC. Thus, cryopreserved MSCs promote immunomodulatory and neuroprotective effects in rats with spinal cord injury by increasing IL-10, GDNF, and VEGF expression and reducing TNF-α and TGF-β expression.
Departmento de Medicina Veterinária, Universidade de Uberaba, Uberaba, MG, Brasil isabelrrosado@yahoo.com.br.
I R
IR
Rosado
Escola de Medicina Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
P H
PH
Carvalho
Departmento de Medicina Veterinária, Universidade de Uberaba, Uberaba, MG, Brasil.
E G L
EG
Alves
Escola de Medicina Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
T M
TM
Tagushi
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
J L
JL
Carvalho
Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.
J F
JF
Silva
Departamento de Ciências Agrárias e Ambientais, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.
M S L
MS
Lavor
Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
K M
KM
Oliveira
Escola de Medicina Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
R
R
Serakides
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
A M
AM
Goes
Escola de Medicina Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
E G
EG
Melo
D000818:Animals; D015925:Cryopreservation / Q000379:methods; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D018696:Neuroprotective Agents / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D044968:Regenerative Medicine / Q000379:methods*; D013119:Spinal Cord Injuries / Q000276:immunology / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10