scholarly journals Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects

Cartilage ◽  
2017 ◽  
Vol 10 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Elhussein Elbadry Mahmoud ◽  
Naosuke Kamei ◽  
Goki Kamei ◽  
Tomoyuki Nakasa ◽  
Ryo Shimizu ◽  
...  

Objective The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. Design At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups ( n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. Results At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. Conclusion An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.

Cartilage ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 410-416 ◽  
Author(s):  
Timea Spakova ◽  
Judita Amrichova ◽  
Jana Plsikova ◽  
Denisa Harvanova ◽  
Slavomir Hornak ◽  
...  

Objective This study aimed to compare microfracture and application of adipose-derived stem cells (ADSCs) by local adherent technique enhanced by platelet-rich plasma (PRP) to provide a new approach for the repair of cartilage defect. Design Full-thickness cylindrical defects were created in the medial femoral condyle in 9 New Zealand White rabbits (5 months old, 4.65 ± 0.20 kg). Two groups of rabbits ( n = 3) were either treated with ADSCs (Group 1) or the microfracture technique (Group 2) following intraarticular injection of PRP 3 times in weekly intervals. Rabbits in control group ( n = 3) remained untreated. The outcome was assessed macroscopically, histologically, and immunohistochemically. Results At the end of week 12, Group 1 showed better defect filling compared with Group 2. Specimens treated with the combination of ADSCs and PRP exhibited significant differences from the other groups in all criteria of International Cartilage Repair Society macroscopic scoring system. Conclusions Intraarticular injection of autologous PRP in combination with transplantation of autologous ADSCs by local adherent technique enhances the quality of cartilage defect repair with better results in comparison with microfracture surgery in a rabbit model.


Author(s):  
Sergei P. Rubnikovich ◽  
Igor D. Volotovsky ◽  
Yulia L. Denisova ◽  
Тatiana E. Vladimirskaya ◽  
Vasilina A. Andreeva ◽  
...  

A promising scope of modern scientific research is the use of autologous and allogeneic mesenchymal stem cells for regeneration of periodontal tissues. The aim of the study was to evaluate the nature of morphological changes in the pathologically altered periodontal tissues after injection of a biotransplant containing mesenchymal stem cells of the adipose tissue immobilized on a collagen carrier in an animal experiment. In the experiment, 60 randobbred females of white rats were used as a model, whose adipose tissue was taken to obtain allogenic mesenchymal stem cells. All animals were divided into 5 groups, depending on the planned method of treatment – 10 rats each. The control group consisted of 10 laboratory animals with healthy gingiva. The experimental gingival recession model was created by the V-shaped excision of periodontal tissues. The bioplastic collagen material “Collost” gel 7 % in isolated form determines the fibrosis intensification and serves as a “matrix” for the formation of a fibrous tissue, ensures the adhesion of stem cells and their transformation into pro- and fibroblasts. Injection of a cell transplant suspension into physiological saline activates the processes of cell proliferation and transformation of fibroblast differentiating cells. Suspension of the cell transplant on a sterile bioplastic collagen material “Collost” gel 7 % enhances the effects of gel and stem cells, promotes the leveling of atrophic and dystrophic changes in the gum, strengthening a mechanical component, reducing the recession of the gum and the depth of the gingival pocket.


Cartilage ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Takahiro Enomoto ◽  
Ryuichiro Akagi ◽  
Yuya Ogawa ◽  
Satoshi Yamaguchi ◽  
Hiroko Hoshi ◽  
...  

Objective We investigated the effect of administration of intra-articular mesenchymal stem cells (MSCs) on cartilage repair at different timings, and the distribution of MSCs in the knee. Design A partial thickness cartilage defect (PTCD) was created on the medial femoral condyle in 14-week-old Sprague-Dawley rats. Intra-articular injection of 1 × 106 MSCs was performed at 3 time points, namely at the time of surgery (0w group), at 1 week after surgery (1w group), and at 2 weeks after surgery (2w group). For the control, 50 μL phosphate-buffered saline was injected at the time of surgery. The femoral condyles were collected at 6 weeks after creation of PTCD and assessed histologically. To investigate the distribution of MSCs, fluorescent-labeled MSCs were injected into the knee joint. Results In the control group, the cartilage lesion was distinguishable from surrounding cartilage. In the 0w group, hypocellularity and a slight decrease in safranin O stainability were observed around the injured area, but cartilage was restored to a nearly normal condition. In contrast, in the 1w and 2w groups, the cartilage surface was irregular and safranin O stainability in the injured and surrounding areas was poor. Histological score in the 0w group was significantly better than in the control, 1w, and 2w groups. At 1 day postinjection, fluorescent-labeled MSCs were mostly distributed in synovium. However, no migration into the PTCD was observed. Conclusions Early intra-articular injection of MSCs was effective in enhancing cartilage healing in a rat PTCD model. Injected MSCs were distributed in synovium, not in cartilage surrounding the PTCD.


2020 ◽  
Author(s):  
Fatemeh Dehghani Nazhvani ◽  
Iman Haghani ◽  
Seifollah Dehghani Nazhvani ◽  
Fatemeh Namazi ◽  
Abbas Ghaderi

Abstract Background: Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model.Methods: Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma.Results: After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies.Conclusion: Liver cirrhosis was induced successfully. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status, as cirrhotic livers were regenerated back into normal parenchyma. Rats’ clinical behavior also reached healthy status.


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).


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.


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