Enhancing therapeutic effects and in vivo tracking of adipose tissue derived mesenchymal stem cells for liver injury using bioorthogonal click chemistry

Nanoscale ◽  
2020 ◽  
Author(s):  
Naishun Liao ◽  
Da Zhang ◽  
Ming Wu ◽  
Huang-Hao Yang ◽  
Xiaolong Liu ◽  
...  

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...

2021 ◽  
pp. 327-343
Author(s):  
L LIU ◽  
F YANG

Acute and chronic hepatitis, cirrhosis, and other liver diseases pose a serious threat to human health; however, liver transplantation is the only reliable treatment for the terminal stage of liver diseases. Previous researchers have shown that mesenchymal stem cells (MSCs) are characterized by differentiation and paracrine effects, as well as anti-oxidative stress and immune regulation functions. When MSCs are transplanted into animals, they migrate to the injured liver tissue along with the circulation, to protect the liver and alleviate the injury through the paracrine, immune regulation and other characteristics, making mesenchymal stem cell transplantation a promising alternative therapy for liver diseases. Although the efficacy of MSCs transplantation has been confirmed in various animal models of liver injury, many researchers have also proposed various pretreatment methods to improve the efficacy of mesenchymal stem cell transplantation, but there is still lack a set of scientific methods system aimed at improving the efficacy of transplantation therapy in scientific research and clinical practice. In this review, we summarize the possible mechanisms of MSCs therapy and compare the existing methods of MSCs modification corresponding to the treatment mechanism, hoping to provide as a reference to help future researchers explore a safe and simple transplantation strategy.


2019 ◽  
Vol 7 (8) ◽  
pp. 1252-1258 ◽  
Author(s):  
Vivi Sofia ◽  
Moch Saiful Bachri ◽  
Rizki Rahmadian

BACKGROUND: Pharmacological therapy in the management of OA causes many new health problems due to side effects caused by long-term use of drugs, such as long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) will cause gastric ulcers and impaired kidney function. In OA pathogenesis, PGE2 gene is involved in the inflammation process. AIM: This study aims to identify the influence of Wharton Jelly Mesenchymal Stem Cell (MSC-WJ) on PGE2 expression gene in synoviocyte by in vitro. MATERIAL AND METHODS: The method used in this study is the co-culture method of primary cells and stem cells in the appropriate media. This research is pure experimental research. The sample used came from synovial tissue of osteoarthritis patients who underwent Total Knee Replacement (TKR) surgery. This study was divided into 6 groups treated with 4 replications. The expression analysis of the Prostaglandin E2 gene was done using qPCR (Real-Time Polymerase Chain Reaction). The expression analysis of the Prostaglandin E2 gene was carried out before and after the co-culture with Wharton's Jelly and continued with the analysis of statistical data processing using the SPSS.15 program. PGE2 gene expression data were processed using the Kruskal-Wallis test and continued with the Mann-Whitney test with a 95% confidence level. RESULTS: The results showed that Mesenchymal Stem Cells Wharton Jelly could reduce the expression of Prostaglandin E2 gene after co-culture for 24 hours and 48 hours in synoviocyte cells osteoarthritis significantly compared with the control group. The administration of Mesenchymal Stem Cells for 24 hours reduced the expression level of PGE2 gene by 0.61 times compared to the control group (p < 0.05) and the administration of Mesenchymal Stem Cells for 48 hours decreased the expression level of PGE2 gene by 0, 47 times compared to the control group (p < 0.05). CONCLUSION: This study concluded that MSC-WJ in OA synoviocyte significantly reduced the expression of the PGE2 gene (p < 0.05).


2017 ◽  
Vol 4 (S) ◽  
pp. 141
Author(s):  
Umul Hanim Yusoff ◽  
Shamsi Ebrahimi

Background: A nifty propagating of mesenchymal stem cell (MSCs) diligence has germinated all over the world by innovative investigators. However, the clinical and basic research applications of MSC requires novel finding biomaterials interfacial interaction especially in sustainable the morphology, physiology, multipotent and phenotypically in long-term cultivation. A prominent of biomaterials benefit to MSCs culture has triggered the multitudinous field especially in regenerative medicine. In order to hinder the deprivation of MSCs in purity and potency, the alternative cell-substrate materials of MSCs culture is essentially to be discovered. This has instigated the idea to encountered the method of screening libraries organic and inorganics biomaterials in bio-adhesively, free ethically, and sustainability to support the morphologically, physiologically, multi-potent and phenotypically of substrates coating cover slip.  Methods: Libraries of inorganic biomaterials substrates have been collected from co-researcher to conduct the initial screening phase of 100 myriad fabrications of substrates whereas enumerated as a Graphene Oxide (GO), Hydroxyapatite (HAp), and Bioactive Glass (BAG) coated cover slip and discs also several organic biomaterials. Wharton’s Jelly derived Mesenchymal Stem Cells (WJMSCs) and Denuded Amnion Mesenchymal Stem Cells (AMMSCs) have been seeded on each substrate in the 48-well plate. Top four leading substrates have been selected for further cultivation until up to 5 passage (>P5) for long term screening known as scaling up phase. Several parameters such as cell attachment, cell viability, kinetic growth, cell-materials osteogenic and adipogenic differentiation and cell phenotype have been analyzed. Top one cell-material culture will go forward to further long-term cultivation up to Passage 10(>P10).  Results: Morphologically and phenotypically demonstrated that GOy1WJMSC showed the significance result among others.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Lukun Zhou ◽  
Shuang Liu ◽  
Zhao Wang ◽  
Jianfeng Yao ◽  
Wenbin Cao ◽  
...  

Abstract Background Liver injury associated with acute graft-versus-host disease (aGVHD) is a frequent and severe complication of hematopoietic stem cell transplantation and remains a major cause of transplant-related mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) has been proposed as a potential therapeutic approach for aGVHD. However, the therapeutic effects are not always achieved. In this study, we genetically engineered C57BL/6 mouse BM-MSCs with AKT1 gene and tested whether AKT1-MSCs was superior to control MSCs (Null-MSCs) for cell therapy of liver aGVHD. Results In vitro apoptosis analyses showed that, under both routine culture condition and high concentration interferon-γ (IFN-γ) (100ng/mL) stimulation condition, AKT1-MSCs had a survival (anti-apoptotic) advantage compared to Null-MSCs. In vivo imaging showed that AKT1-MSCs had better homing capacity and longer persistence in injured liver compared to Null-MSCs. Most importantly, AKT1-MSCs demonstrated an enhanced immunomodulatory function by releasing more immunosuppressive cytokines, such as IL-10. Adoptive transfer of AKT1-MSCs mitigated the histopathological abnormalities of concanavalin A(ConA)-induced liver injury along with significantly lowered serum levels of ALT and AST. The attenuation of liver injury correlated with the decrease of TNF-α and IFN-γ both in liver tissue and in the serum. Conclusions In summary, BM-MSCs genetically modified with AKT1 has a survival advantage and an enhanced immunomodulatory function both in vitro and in vivo and thus demonstrates the therapeutic potential for prevention and amelioration of liver GVHD and other immunity-associated liver injuries.


Stem Cells ◽  
2008 ◽  
Vol 26 (10) ◽  
pp. 2705-2712 ◽  
Author(s):  
Agnieszka Banas ◽  
Takumi Teratani ◽  
Yusuke Yamamoto ◽  
Makoto Tokuhara ◽  
Fumitaka Takeshita ◽  
...  

2020 ◽  
Author(s):  
Daniela Franco Bueno ◽  
Gerson Shigueru Kabayashi ◽  
Carla Cristina Gomes Pinheiro ◽  
Daniela Y S Tanikawa ◽  
Cassio Eduardo Raposo-Amaral ◽  
...  

Abstract Background. Bone reconstruction in congenital craniofacial differences, which affect about 2-3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stem cells in regenerative medicine protocols has opened a new field of investigation aimed at finding optimal sources of multipotent stem cells that can be isolated via non-invasive procedures. Here we analysed whether levator veli palatini muscle fragments, which can be readily obtained in non-invasive manner during surgical rehabilitation of cleft p­­atients during palatoplasty, represent a novel source of MSCs with osteogenic potential. Methods. We obtained levator veli palatini muscle fragments, in non-invasive procedure during surgical rehabilitation of 5 unrelated cleft palate patients (palatoplasty surgery). The levator veli palatini muscle fragments was used to obtain the mesenchymal cells using pre-plating technique in a clean rooms infrastructure and all procedures were performed at good practices of manipulation conditions. To prove that levator veli palatini muscle are mesenchymal stem cells they were induced to flow cytometry analysis and to differentiation into bone, cartilage, fat and muscle. To demonstrate the osteogenic potential of these cells in vivo a bilateral full thickness calvarial defect model was made in immunocompentent rats.Results. Flow cytometry analysis showed that the cells were positive for mesenchymal stem cell antigens (CD29, CD73, CD90), while negative for hematopoietic (CD45) or endothelial cell markers (CD31). Moreover, these cells were capable of undergoing chondrogenic, adipogenic, osteogenic and skeletal muscle cell differentiation under appropriate cell culture conditions characterizing them as mesenchymal stem cell. Defects treated with CellCeramTM scaffolds seeded with levator veli palatini muscle cells showed significantly greater bone healing compared to defects treated with acellular scaffolds. Conclusion. We have demonstrated that cells derived from levator veli palatini muscle have phenotypic characteristics similar to other mesenchymal stem cells, both in vitro and in vivo. Our findings suggest that these cells may have clinical relevance in the rehabilitation of patients with cleft palate and other craniofacial anomalies characterized by significant bone deficit.


2014 ◽  
Vol 26 (1) ◽  
pp. 216 ◽  
Author(s):  
H. N. Malik ◽  
A. Dubey ◽  
D. K. Singhal ◽  
S. Saugandhika ◽  
S. Boeteng ◽  
...  

Adult stem cells derived from all possible sources of livestock serve as the best possible alternative to embryonic stem cells. The discovery of mesenchymal stem cells has provided the new horizon to stem cell therapy. Adipose tissue derived mesenchymal stem cell (ADSCs), an easy source of adult stem cell has created a lot of interest among researchers as patient specific treatment and autologous transplantation in animals is becoming a viable option. The proposed study was carried out for 1) isolation of ADSCs from dogs, suffering from hip dysplasia or from paraplegia, 2) ADSC characterisation and in vitro differentiation ability into osteocytes, chondrocytes, adipocytes and neurocytes specific cells. Adipose tissues were collected from belly/umbilical cord region. ADSCs were isolated by enzymatic digestion method followed by enriching through a 41 μm filter. Filtered cells were then resuspended in cell culture flasks containing growth enriching medium and cultured in 5% CO2 in air at 37°C for 5 days. ADSCs were characterised by amplification of mesenchymal stem cell specific markers i.e. CD29, CD44, CD90, and CD166 and by immunocytochemistry of mesenchymal stem cell specific protein i.e. CD44 and CD90. ADSCs were further in vitro differentiated. ADSCs derived osteocytes, chondrocytes, and adipocytes were validated through the amplification of specific markers of osteocytes (Osteopontin, Collagen I); chondrocytes (Aggrecan and Collagen II) and adipocytes (LPL, PPARα, PPARγ). Dog ADSCs were further autogenic transplanted into hip dysplasia and paraplegic patients. These patients recovered well one month from transplantation and were able to move freely. It may be concluded that these findings may have implications for defining the physiological roles of ADSCs in arthritis; orthopaedic ailments, joint regeneration, neuronal disorders, and several other applications leading to novel therapeutic opportunities.


2013 ◽  
Vol 16 (4) ◽  
pp. 753-754 ◽  
Author(s):  
J. Nicpoń ◽  
K. Marycz ◽  
J. Grzesiak

Abstract In this article we demonstrate the efficiency of autologous transplantations of adipose-derived mesenchymal stem cells for equine bone spavin treatment. Horses qualified to the study were divided into three groups: (i) research - treated with intra-articular injections of autologous stem cells, (ii) comparison treated with steroid drugs and (iii) control - untreated. All animals underwent comprehensive clinical examination before and after treatment. Our research confirms the long-term beneficial influence resulting from stem cell therapy in horse bone spavin treatment, in contrast to routine steroid usage.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Takahiro Teshima ◽  
Hirotaka Matsumoto ◽  
Masaki Michishita ◽  
Akito Matsuoka ◽  
Maika Shiba ◽  
...  

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are an attractive source for cell-based therapy of some diseases, including acute and chronic liver failure, in not only human medicine but also veterinary medicine. However, in veterinary medicine, no studies have reported the effects of AT-MSCs on liver injury in dogs. The purpose of this study was to investigate the effects of allogenic AT-MSCs on acute liver injury by carbon tetrachloride in dogs and to compare the therapeutic effects of AT-MSCs transplanted via the peripheral vein (PV) or splenic vein (SV). After transplantation of AT-MSCs through the PV or SV, serum liver enzymes were decreased significantly, and SV injection was more effective compared with PV injection. By comparing the number of engrafted AT-MSCs in the liver, SV injection was significantly more effective than PV injection. mRNA expression levels of proinflammatory cytokines, such as IL-1, IL-6, IL-8, and IFNγ, in the liver were decreased significantly, but those of anti-inflammatory cytokines, such as IL-4 and IL-10, HGF, and VEGFA, were significantly increased after the first AT-MSC injection. These findings suggest that allogenic AT-MSCs injected via the PV or SV ameliorate acute hepatic injury in dogs, and AT-MSCs injected via the SV provide more effective improvement.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Feridoun Parnia ◽  
Javad Yazdani ◽  
Solmaz Maleki Dizaj

The potential application of stem cell biology in human dentistry is a new and emerging field of research. The objective of the current review was to study the efficiency of mesenchymal stem cells (MSCs) in sinus lift augmentation (SLA). A literature review was performed in PubMed Central using MeSH keywords such as sinus lift, MSCs, dental implants, and augmentation. The searches involved full-text papers written in English, published in the past 10 years (2007–2017). The review included in vitro and in vivo studies on the use of MSCs in SLA. Electronic searching provided 45 titles, and among them, 8 papers were chosen as suitable based on the inclusion requirements of this review. The reviewed studies have revealed the potential of MSCs in SLA. According to these papers, stem cell therapy combined with different biomaterials may considerably improve bone regeneration in previous steps of dental implantation and may veritably lead to efficient clinical usages in the recent future. However, the identification of an ideal source of stem cells as well as long-term studies is vital to assess the success rate of this technology. Further clinical trials are also needed to approve the potential of MSCs in SLA.


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