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. 2024 Mar 18;20(1):110.
doi: 10.1186/s12917-024-03912-4.

Evaluation of canine adipose-derived mesenchymal stem cells for neurological functional recovery in a rat model of traumatic brain injury

Wenkang Jiang #  1   2 , Huina Luo #  2 , Mingming Zhao  2 , Quanbao Fan  2 , Cailing Ye  3 , Xingying Li  2 , Jing He  2 , Jianyi Lai  2 , Shi He  2 , Wojun Chen  2 , Weihang Xian  2 , Shengfeng Chen  2 , Zhisheng Chen  2 , Dongsheng Li  4 , Ruiai Chen  5 , Bingyun Wang  6
Affiliations

Evaluation of canine adipose-derived mesenchymal stem cells for neurological functional recovery in a rat model of traumatic brain injury

Wenkang Jiang et al. BMC Vet Res. .

Abstract

Background: Traumatic brain injury (TBI) is a common condition in veterinary medicine that is difficult to manage.Veterinary regenerative therapy based on adipose mesenchymal stem cells seem to be an effective strategy for the treatment of traumatic brain injury. In this study, we evaluated therapeutic efficacy of canine Adipose-derived mesenchymal stem cells (AD-MSCs)in a rat TBI model, in terms of improved nerve function and anti-neuroinflammation.

Results: Canine AD-MSCs promoted neural functional recovery, reduced neuronal apoptosis, and inhibited the activation of microglia and astrocytes in TBI rats. According to the results in vivo, we further investigated the regulatory mechanism of AD-MSCs on activated microglia by co-culture in vitro. Finally, we found that canine AD-MSCs promoted their polarization to the M2 phenotype, and inhibited their polarization to the M1 phenotype. What's more, AD-MSCs could reduce the migration, proliferation and Inflammatory cytokines of activated microglia, which is able to inhibit inflammation in the central system.

Conclusions: Collectively, the present study demonstrates that transplantation of canine AD-MSCs can promote functional recovery in TBI rats via inhibition of neuronal apoptosis, glial cell activation and central system inflammation, thus providing a theoretical basis for canine AD-MSCs therapy for TBI in veterinary clinic.

Keywords: Adipose-derived mesenchymal stem cells; Attenuating inflammation; Microglia; Therapy; Traumatic brain injury.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Modified neurological severity score. **indicates p < 0.01; *indicates p < 0.05
Fig. 2
Fig. 2
Serum inflammatory factors of rats on the 3rd day were detected by ELISA. **indicates p < 0.01; *indicates p < 0.05
Fig. 3
Fig. 3
AD-MSCs inhibits the expression of IBA1. A The mRNA expression of microglia marker IBA1 in brain tissue was detected by qPCR; B The localized expression of microglia marker IBA1 protein was detected by immunofluorescence; C Relative intensity of IBA1. **indicates p < 0.01; *indicates p < 0.05. Scale bar is 200 μm
Fig. 4
Fig. 4
AD-MSCs inhibits the expression of GFAP. A The mRNA expression of astrocytemarker GFAP in brain tissue was detected by qPCR; B The localized expression ofastrocyte marker GFAP protein was detected by immunofluorescence; C Relative intensity of GFAP. **indicates p < 0.01; *indicates p < 0.05. Scale bar is 200 μm
Fig. 5
Fig. 5
AD-MSCs limited the apoptosis of neural cells. A The localized expression of neural cells marker NeuN protein was detected by immunohistochemistry; B Relative intensity of NeuN. C The mRNA expression of neural cells marker NeuN in brain tissue was detected by qPCR. D The expression of Bcl2/Bax apoptosis-related genes was detected by qPCR. **indicates p < 0.01; *indicates p < 0.05.Scale bar is 100 μm
Fig. 6
Fig. 6
HE staining of rat brain tissue. Scale bar is 100 μm
Fig. 7
Fig. 7
AD-MSCs reduced the proliferation of LPS-activated BV2 cells. A-B The effects of canine AD-MSCs on the proliferation of activated BV2 cells after 24 and 48 h were detected by microplate reader. C The mRNA expression of CCND1 genes of BV2 cells was detected by qPCR. **indicates p < 0.01; *indicates p < 0.05
Fig. 8
Fig. 8
AD-MSCs inhibited the migration of LPS-activated BV2 cells. A and C The migration photo of BV2 cells at 6 and 12 h were analyzed using Image J software v1.8. B The migration photo of BV2 cells. **indicates p < 0.01; *indicates p < 0.05
Fig. 9
Fig. 9
The effect of AD-MSCs on polarization of BV2 cells. A and B The mRNA expression of Arg-1 and CD86 genes of BV2 cells was detected by qPCR. **indicates p < 0.01; *indicates p < 0.05
Fig. 10
Fig. 10
The effect of AD-MSCs on the expression of inflammatory cytokines of BV2 cells. A and C The mRNA expression of IL-6 and TNF-α genes of BV2 cells were detected by qPCR. B and D The mRNA expression of IL-6 and TNF-α protein were detected by ELISA. **indicates p < 0.01; *indicates p < 0.05
Fig. 11
Fig. 11
AD-MSCs reduced LPS-induced production of NO by microglial cells. A The mRNA expression of iNOS genes of BV2 cells were detected by qPCR. B NO secretion level of BV2 cells were detected by Total Nitric Oxide Assay Kit. **indicates p < 0.01; *indicates p < 0.05
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