Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration

被引:33
作者
Cunha, Carla [1 ,2 ]
Almeida, Catarina R. [1 ,2 ,3 ]
Almeida, Maria Ines [1 ,2 ]
Silva, Andreia M. [1 ,2 ,4 ]
Molinos, Maria [1 ,2 ,4 ]
Lamas, Sofia [1 ,5 ]
Pereira, Catarina L. [1 ,2 ,4 ]
Teixeira, Graciosa Q. [1 ,2 ,4 ]
Monteiro, Antonio T. [6 ]
Santos, Susana G. [1 ,2 ]
Goncalves, Raquel M. [1 ,2 ]
Barbosa, Mario A. [1 ,2 ,4 ]
机构
[1] Univ Porto, I3S Inst Invest & Inovacao Saude, P-4100 Oporto, Portugal
[2] Univ Porto, INEB Inst Engn Biomed, P-4100 Oporto, Portugal
[3] Univ Aveiro, Inst Biomed, Dept Med Sci, P-3800 Aveiro, Portugal
[4] Univ Porto, ICBAS Inst Ciiencias Biomed Abel Salazar, P-4100 Oporto, Portugal
[5] Univ Porto, IBMC Inst Biol Mol Celular, P-4100 Oporto, Portugal
[6] Res Ctr Biodivers & Genet Resources, CIBIO InBIO Associate Lab, Vairao, Portugal
关键词
Intravenous transplantation; Cell therapy; Herniation; Immunomodulation; Paracrine; NUCLEUS PULPOSUS; DEGENERATION MODEL; STROMAL CELLS; INFLAMMATORY CELLS; ENDOGENOUS REPAIR; DENDRITIC CELLS; ORGAN-CULTURE; DIFFERENTIATION; THERAPY; IDENTIFICATION;
D O I
10.5966/sctm.2016-0033
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bonemarrowmesenchymal stemcells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed. Disc height index and histological grading score indicated less degeneration for theMSC-transplanted group, with no significant changes in extracellular matrix composition. Remarkably, MSC transplantation resulted in local downregulation of the hypoxia responsive GLUT-1 and in significantly less herniation, with higher amounts of Pax5+ B lymphocytes and no alterations in CD68+ macrophages within the hernia. The systemic immune responsewas analyzed in the blood, draining lymph nodes, and spleen by flow cytometry and in the plasma by cytokine array. Results suggest an immunoregulatory effect in the MSC-transplanted animals compared with control groups, with an increase in MHC class II+ and CD4+ cells, and also upregulation of the cytokines IL-2, IL-4, IL-6, and IL-10, and downregulation of the cytokines IL-13 and TNF-alpha. Overall, our results indicate a beneficial effect of systemically transplanted MSCs on in situ IVD regeneration and highlight the complex interplay between stromal cells and cells of the immune system in achieving successful tissue regeneration.
引用
收藏
页码:1029 / 1039
页数:11
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