scholarly journals Encapsulated Allogeneic Synovial Membrane Mesenchymal Stem Cells Provide Better Outcomes of Chondral Lesions in Horses

Author(s):  
Vitor Hugo Santos ◽  
João Pedro Hübbe Pfeifer ◽  
Gustavo dos Santos Rosa ◽  
Fernanda de Castro Stievani ◽  
Emanuel Vitor Pereira Apolonio ◽  
...  

Abstract Osteoarthritis is the main cause of equine lameness, and its treatment remains ineffective. Synovial membrane mesenchymal stem cells (SMMSCs) provide satisfactory outcomes in joint injuries, mainly due to their immunomodulatory and reparative properties. This study aimed to evaluate the effect of SMMSCs, either encapsulated in alginate hydrogel or free, in chondral lesions of horses.Methods: Chondral lesions were surgically induced in the medial trochlea of the talus of fifteen horses. Animals were treated with PBS free SMMSCs or encapsulated SMMSCs. Physical evaluations, assignment of lameness scores and synovial fluid analysis were performed (cytological analysis and dosage of IL-1, IL-10, IL-6, INF-Ɣ, TNF 𝛼, P substance, serum amyloid A, TGF-β, IGF and PGE2) for two weeks. Cartilage biopsies were performed 150 days after induction for histological analysis and immunohistochemistry staining.Results: All groups initially presented inflammation. Although free SMMSCs showed moderate tissue repair, encapsulated SMMSCs had a lower grade of inflammation with superior tissue macro- and microscopic aspects at the end, while the control group showed fibrosis and poor cartilage aspect. This study suggests better effectiveness of stem cells in chondral defects when encapsulated MSCs are used.Conclusion: While the absence of treatment perpetuates cartilage degradation, encapsulated SMMSCs respond better to initial inflammation, interacting and modulating the environment through the release of anti-inflammatory cytokines. Better outcomes observed in encapsulated MSCs were related to the immuno- and physical barriers provided by the alginate hydrogel, allowing a longer period of permanence and interaction between MSCs and the environment.

2021 ◽  
Author(s):  
Vitor Hugo Santos ◽  
João Pedro Hübbe Pfeifer ◽  
Fernanda de Castro Stievani ◽  
Gustavo Santos Rosa ◽  
Emanuel Vitor Pereira Apolonio ◽  
...  

Abstract BackgroundOsteoarthritis is the main cause of equine lameness and its treatment remains ineffective. Synovial membrane mesenchymal stem cells (SMMSC) provide satisfactory outcomes in joint injuries, mainly due to their immunomodulatory and reparative properties. This study aimed to evaluate the effect of MSMSC, either encapsulated in alginate hydrogel or free, in chondral lesions of horses.MethodsChondral lesions were surgically induced in medial trochlea of talus of fifteen horses. Animals were treated with PBS, 1x107 free SMMSC or 1x107 encapsulated SMMSC. Physical evaluations, lameness scores and synovial fluid analysis were determined (cytological analysis and dosage of IL-1, IL-10, IL-6, INF-Ɣ, TNF 𝛼, P Substance, Serum Amyloid A, TGF-β, IGF and PGE2) initially and followed for up to two weeks. Cartilage biopsies were performed 150 days after the induction for histological analysis and immunohistochemistry staining.ResultsAll groups presented inflammation initially. Although free SMMSC showed moderate tissue repair, encapsulated SMMSC modulated inflammation and had the lower grade of inflammation with superior tissue macro and microscopic aspects at the end, while the control group showed fibrosis and poor cartilage appearance. This study suggests better stem cell effectiveness in chondral defects when encapsulated MSCs are used.ConclusionsWhile the absence of treatment perpetuates cartilage degradation, encapsulated SMMSC responded better to the initial inflammation, interacting and modulating the environment through the release of anti-inflammatory cytokines. Better outcomes observed in encapsulated MSCs were related to the immuno and physical barrier provided by the alginate hydrogel, allowing a longer period of permanence and interaction between MSCs and the environment.


2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Vitor Hugo Santos ◽  
João Pedro Hübbe Pfeifer ◽  
Jaqueline Brandão de Souza ◽  
Betsabéia Heloisa Gentilha Milani ◽  
Rogério Antonio de Oliveira ◽  
...  

2018 ◽  
Vol 14 (1) ◽  
Author(s):  
Vitor Hugo Santos ◽  
João Pedro Hübbe Pfeifer ◽  
Jaqueline Brandão de Souza ◽  
Betsabéia Heloisa Gentilha Milani ◽  
Rogério Antonio de Oliveira ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Lan ◽  
Fang Liu ◽  
Lixian Chang ◽  
Lipeng Liu ◽  
Yingchi Zhang ◽  
...  

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).


Author(s):  
Ana A. Aldana ◽  
Marina Uhart ◽  
Gustavo A. Abraham ◽  
Diego M. Bustos ◽  
Aldo R. Boccaccini

Abstract3D printing has emerged as vanguard technique of biofabrication to assemble cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissues. In this work, gelatin methacrylate (GelMA)/alginate hydrogel scaffolds were obtained by 3D printing and 14-3-3ε protein was encapsulated in the hydrogel to induce osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASC). GelMA/alginate-based grid-like structures were printed and remained stable upon photo-crosslinking. The viscosity of alginate allowed to control the pore size and strand width. A higher viscosity of hydrogel ink enhanced the printing accuracy. Protein-loaded GelMA/alginate-based hydrogel showed a clear induction of the osteogenic differentiation of hASC cells. The results are relevant for future developments of GelMA/alginate for bone tissue engineering given the positive effect of 14-3-3ε protein on both cell adhesion and proliferation.


Heart Rhythm ◽  
2010 ◽  
Vol 7 (11) ◽  
pp. 1714
Author(s):  
Nikhil C. Panda ◽  
Sean Zuckerman ◽  
KeKe Fan ◽  
Devi Gopinath ◽  
David S. Rosenbaum ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Man Amanat ◽  
Anahita Majmaa ◽  
Morteza Zarrabi ◽  
Masoumeh Nouri ◽  
Masood Ghahvechi Akbari ◽  
...  

Abstract Background This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. Methods Participants (4–14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). Results There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen’s d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen’s d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (−1.0; 95%CI −1.31, −0.69) and control (β −0.72; 95%CI −1.18, −0.26; Cohen’s d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST −0.035 × 10-3; 95%CI −0.04 × 10-3, −0.02 × 10-3. PTR −0.045 × 10-3; 95%CI −0.05 × 10-3, −0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. Conclusions The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. Trial registration The study was registered with ClinicalTrials.gov (NCT03795974).


2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.


2021 ◽  
Vol 11 (8) ◽  
pp. 1576-1581
Author(s):  
Yiwei Shen ◽  
Xue Li ◽  
Xiaoke Wu ◽  
Yi Li ◽  
Yiwei Shen ◽  
...  

SIRT1 is known to be closely associated with cellular senescence, while the relationship between miR-487a-3p and SIRT1 and their role in mesenchymal stem cells (MSCs) remains unclear. MiRDB analysis showed SIRT1 is a target of miR-487a-3p. Here we investigated whether miR-487a-3p modulates senescence of mesenchymal stem cells by targeting SIRT1. The human MSCs (hMSCs) were divided into control group (NC group), miR-487a-3p Mimics group, pCMV-SIRT+miR-487a-3p Mimics group followed by analysis of miR-487a-3p expression by qPCR and protein level of SIRT1, P21 and P53 by western blot. Dual luciferin report assay verified the binding of miR-487a-3p to SIRT1 mRNA and β-galactosidase activity staining detected hMSCs senescence. miR-487a-3p level was significantly elevated after miR-487a-3p Mimics treatment (P <0.01) without difference between miR-487a-3p Mimics group and pCMV-SIRT1 group+miR-487a-3pMimics (P >0.05). miR-487a-3p mimics significantly decreased SIRT1 level (P < 0.01), which was reversed by pCMVSIRT1 plasmid transfection (P <0.05). Moreover, miR-487a-3p could bind SIRT1 mRNA 3′-UTR region. Further more, miR-487a-3p Mimics induced cellular senescence as displayed by increased β-galactosidase activity (P <0.01) and increased level of senescence-related proteins P21 and P53 (P < 0.01), which were all reversed by overexpression of SIRT1 (P < 0.05). In conclusion, miR-487a-3p reduced SIRT1 expression, thus promoting hMSCs senescence, while overexpression of SIRT1 could counteract the senescence of hMSCs induced by miR-487a-3p.


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