Assessment of Therapeutic Efficacy of Mesenchymal Stem Cells in Doxorubicin- Induced Skeletal Myopathy: A histological and Immunological Experimental Study

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 35-44
Author(s):  
Ahmed H. Bayoumi ◽  
Ahmed El Zainy ◽  
Amul M. Badr ◽  
Dina Fawzy ◽  
Amal A. Elshimy

Background: Doxorubicin is an effective chemotherapeutic drug that commonly induce pathological alteration in skeletal muscles. Bone- marrow mesenchymal stem cells (BMMSCs) offer a therapeutic potential for tissue repair and regeneration. Tumour necrosis factor-alpha (TNF-α) and Interleukin-1 beta (IL-1β) display worthy biomarkers for tissue damage and repair. Objectives: The aim of the current study was to evaluate the therapeutic effect of BMMSCs on doxorubicin - induced skeletal myopathy in experimental animals, through histological studies, antioxidant activity and investigation of TNF-α, IL-1β as diagnostic parameters for muscle damage and regeneration. Methodology: 40 adult albino-rats were divided into 4 equal groups; Group-I (control group) injected with phosphate-buffered saline (PBS), Group-II: doxorubicin- induced myopathy model group; received no treatment, Group-III: doxorubicin- induced myopathy model left for spontaneous muscle recovery, and Group-IV: doxorubicin- induced myopathy treated with systemic BMMSCs. The skeletal muscle regeneration evaluated through histological and antioxidant activity studies and investigation of TNF-α, IL-1β and vascular endothelial growth factor (VEGF) levels. Results: Photomicrographic studies of the muscle fibers showed a more evident regeneration in MSCs treated groups (IV) when compared with the other groups received no treatment. A significant reduced levels of TNF-α, IL-1β, and increased both VEGF and antioxidant activity were demonstrated in group IV when compared with the other groups received no treatment. Conclusion: MSCs is a promising therapy for doxorubicin-induced skeletal myopathy. TNF-α, and IL-1β are helpful biomarkers for evaluation of SCs therapeutic efficacy.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Dalia Abdelhafez ◽  
Elshimaa Aboelkomsan ◽  
Abir El Sadik ◽  
Noha Lasheen ◽  
Sara Ashur ◽  
...  

Severe acute pancreatitis (SAP) is a necrotic pancreatic inflammation associated with high mortality rate (up to 70%). Bone marrow (BM) mesenchymal stem cells (MSCs) have been investigated in pancreatic cellular regeneration, but still their effects are controversial. Therefore, the present study is aimed at examining the enrichment of the stem cells with ascorbic acid (AA) and N-acetylcysteine (NAC) and explore their combined action on the expression of the inflammatory cytokines: interleukin 1β (IL 1β), tumor necrosis factor-α (TNF-α), and nuclear factor-κβ (NF-κβ). A total of twenty adult male Sprague-Dawley albino rats were divided into four groups: the control group, cerulein group (to induce acute pancreatitis), BM-MSCs group, and combined BM-MSCs with AA and NAC group. Homing and proliferation of stem cells were revealed by the appearance of PKH26-labelled BM-MSCs in the islets of Langerhans. AA and NAC combination with BM-MSCs (group IV) was demonstrated to affect the expression of the inflammatory cytokines: IL 1β, TNF-α, and NF-κβ. In addition, improvement of the biochemical and histological parameters is represented in increasing body weight, normal blood glucose, and insulin levels and regeneration of the islet cells. Immunohistochemical studies showed an increase in proliferating cell nuclear antigen (PCNA) and decrease in caspase-3 reactions, detected markedly in group IV, after the marked distortion of the classic pancreatic lobular architecture was induced by cerulein. It could be concluded that treatment with BM-MSCs combined with antioxidants could provide a promising therapy for acute pancreatitis and improve the degeneration, apoptosis, necrosis, and inflammatory processes of the islets of Langerhans. TNF-α, IL 1β, and NF-κβ are essential biomarkers for the evaluation of MSC regenerative effectiveness.


2021 ◽  
Vol 11 (Suppl. 1) ◽  
pp. 47-55
Author(s):  
Zozan Erdoğmuş ◽  
Belgin Gülsün

Aim: Deformities of the jaw and face are often caused by infection, inflammation, and cystic and neoplastic pathological conditions. Defects with various aetiologies should be repaired promptly using the most appropriate approach to reconstruct the anatomical form. To treat defects, bone grafts with various combinations have been used. In particular, combinations including cellular products to enhance osteogenic properties have been implemented. In this study, we aimed to investigate the effects of different materials and cells on bone defects by using mesenchymal stem cells (MSCs), which are thought to have a positive effect on healing, demineralized bone graft (DMB) and platelet-rich plasma (PRP). Methodology: We used 55 female rats weighing between 200-250 g, four of which were used to obtain platelet-rich plasma. The remaining animals were divided into five groups. Group I (n = 6) was the operative control group, Group II (n = 24) was given DMB, Group III (n = 24) was given DMB+PRP, Group IV (n = 24) was given MSC+DBG and Group V (n = 24) was given DMB+PRP+MSC applied to rat tibial defects (10 mm x 3 mm x 2 mm). Results: Statistically significant differences were observed in bone osteoblastic activity in tibia defects among the groups (p<0.05). Conclusion: Bone regeneration was significantly improved in groups where MSCs were used in combination with DMB and PRP.   How to cite this article: Erdoğmuş Z, Gülsün B. The effect of mesenchymal stem cells, demıneralızed bone graft and platelet-rıch plasma on osteogenesıs ın rat tıbıa defects. Int Dent Res 2021;11(Suppl.1):47-55. https://doi.org/10.5577/intdentres.2021.vol11.suppl1.8   Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.


2012 ◽  
Vol 27 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Conceição Aparecida Dornelas ◽  
Francisco Vagnaldo Fechine-Jamacaru ◽  
Irineu Lima Albuquerque ◽  
Hemerson Iury Ferreira Magalhães ◽  
Adjair Jairo Silva de Souza ◽  
...  

PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.


2020 ◽  
Author(s):  
kun zhu ◽  
Rui Zhao ◽  
Yuchen Ye ◽  
Gang Xu ◽  
Changchun Zhang

Abstract Background: Disc degenerative disease is a common senile degenerative disease, which seriously affects the quality of life of patients.The purpose of this study is to observe the biological and cytological characteristics of rabbit nucleus pulposus mesenchymal stem cells (NPMSCs), and to determine the effect of growth differentiation factor 5(GDF5) on the differentiation of rabbit NPMSCs by lentivirus transfection.Methods: In vitro culture model of rabbit NPMSCs was established and NPMSCs cells were identified by flow cytometry (FCM)and quantitative real-time PCR(qRT-PCR). Then NPMSCs were divided into three groups: lentiviral vector carrying GDF5 was used to transfect NPMSCs, to determine the transfection rate, which was recorded as transfection group, and the NPMSCs transfected with ordinary lentiviral vector was recorded as control group, NPMSCs without processing was recorded as normal group. FCM, qRT-PCR and Western Blot(WB) were used to detected the change of NPMSCs.Results: The transfected NPMSCs by GDF5 became longer and narrower, and the cell density decreased,and the positive rate of GDF5 in the transfected group was significantly higher than that in the other two groups (P<0.05). The mRNA expression of KRT8, KRT18, KRT19 in the transfected group was significantly higher than the other two groups(P<0.05),the result of WB were the same to qRT-PCR. Conclusions: GDF5 can induce the differentiation of NPMSCs and repair degenerative intervertebral discs. Lentiviral vector carrying GDF5 can be integrated into the chromosome genome of NPMSCs and promote differentiation of NPMSCs into nucleus pulposus cells(NPCs).


2021 ◽  
Author(s):  
Yang Xiaofeng ◽  
Qianqian Wang

Abstract Objective: To investigate the survival ability of bone marrow Mesenchymal stem cells (MSCs) transfected with survinvin gene in the microenvironment of renal ischemia,and to study the ability and mechanism of repairing renal ischemia-reperfusion injury in rats.Method: Mesenchymal stem cells (MSCs) from bone marrow of male Sprague–Dawley rat were infected with the self‐inactive lentiviral vector and transfected with the Survinvin gene recombinant vector and then EGFP-tagged. After amplification and culture, they were detected by green fluorescence and then retained.48 specific pathogen-free C57BL/6J mice were randomly divided into 4 groups of 12 each. Rats in the control group were only surgically exposed. The other 3 groups were surgically exposed and the bilateral renal arteries were clamped for 45 minutes to restore blood supply, and models of renal ischemia-reperfusion were established. There were control group,ischemia reperfusion group(Marked as IR group), empty virus transfection transplantation group(Marked as MSCs group) or survinvin gene transfection transplantation group(Marked as SVV/MSCs group), and sequentially injected with normal saline,normal saline,1×106 MSCs infected with the self‐inactive lentiviral vector or 1×106 survivin gene-expressing MSCs. At different time points of 1d, 3d, 7d, 14d, collect serum to test blood urea nitrogen detection, to cut the rat kidney section for quantitative analysis, HE staining to observe renal issues changes and the degree of renal tubular damage and IL-10 by using ELISA detection. Result: The MSCs with resuscitation and expansion culture had strong proliferation and good fluorescence. The creatinine urea nitrogen level in the MSCs group and SVV/MSCs group was significantly lower than that in the IR group and control group (p<0.01 or p<0.05). The pathological damage score of HE staining in the kidney was lighter in the stem cell transplantation group, and the SVV/MSCs group was significantly lower than the other two groups (p<0.01 or p<0.05). On the 3rd and 14th day, the number of transplanted cells in the kidney tissue was much higher in the SVV/MSCs group than in the MSCs group. The MSCs expressing EGFP were mainly distributed around the glomerulus, the small vessel inner wall, and the interstitial between the renal tubule and the renal tubule. However, MSCs expressing EGFP were hardly seen on the inner wall of the renal tubule. The levels of protective factors IL-10 increased after renal ischemic injury. SVV/MSCs group was also significantly more than IR group or MSCs group (P<0.01 or p<0.05). And there was no statistical difference from the normal control group on the 14th day.Conclusion: Transfection of Survinifin gene can increase the survival ability of MSCs in ischemic kidney. After transplantation, MSCs are not directly differentiated into injured tubular endothelial cells, which further promote the repair of kidney damage through its strong paracrine effect.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7023 ◽  
Author(s):  
Qing Zhang ◽  
Qihong Li ◽  
Jun Zhu ◽  
Hao Guo ◽  
Qiming Zhai ◽  
...  

Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.


2021 ◽  
Vol 11 (4) ◽  
pp. 89-92
Author(s):  
Vyacheslav Mykhaylichenko ◽  
Andrey Pilipchuk ◽  
Dmitry Parshin ◽  
Yuri Kostyamin

Experimental modeling of myocardial infarction in rats was carried out by ligation of the anterior intergastric artery after the first division. There were 3 groups of 20 animals each: control group I — to verify normal parameters, group II — a model of myocardial infarction, and group III — animals which, after modeling myocardial infarction, underwent transplantation of mesenchymal stem cells. The level of lipid peroxidation products — diene conjugates and malondialdehyde — was studied by spectrophotometry. Comparison of the content and their ratio in the cytoplasm and mitochondria of myocardiocytes was carried out. It turned out that transplantation of mesenchymal stem cells significantly levels the activation of lipid peroxidation processes in subcellular fractions of cardiomyocytes, which is accompanied by a decrease in the primary and secondary products of oxidative stress. The ratio of malondialdehyde to diene conjugates both in the cytoplasm and in the mitochondria of cardiomyocytes after transplantation returned to control values. This indicates the normalization of physiological processes with underlying ischemic heart damage. The results indicate the cytoprotective effect of mesenchymal stem cell transplantation and the preservation of a larger number of cell pools, compared with the control group of animals that did not receive any treatment.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
L M Elhosseiny ◽  
A F Badawy ◽  
A M Elashkar ◽  
F A Abuzahra ◽  
N M Abdelsamee ◽  
...  

Abstract Bone marrow-derived mesenchymal stem cells (BM-MSCs) are self-renewing, clonal precursors of non-haematopoietic tissues, with anti-inflammatory and anti-apoptotic effect. This study aimed to evaluate the effect of BM-MSCs on chronic toxoplasmosis. BM-MSCs were isolated from 6-wk-old BALB/c donor male mice, then grown and propagated in culture until cell count was 5–8x106/ml. Female Swiss albino mice were divided into five groups: Group I (infected mice injected with BM-MSCs); Group II (infected mice treated with both BM-MSCs and conventional treatment); Group III (infected mice conventionally treated with Spiramycin-Metronidazole combination); Group IV (infection control group in which mice were infected with Me49 strain of Toxoplasma gondii) and Group V (non-infected mice injected with BM-MSCs). Histopathological examination of brain tissue and survival rate were assessed in each group. Compared to the infection control group and conventionally treated group, the infected mice injected with BM-MSCs showed less tissue damage, mild inflammatory changes in brain sections and low mortality rate. The group treated with both MSCs and conventional treatment showed unexpected sever inflammation and the highest mortality rate.


Author(s):  
Inu Mulyantoro ◽  
Noor Pramono Noerpramana ◽  
Yuda Heru Febrianto ◽  
Widjiati Widjiati ◽  
Purwati Purwati ◽  
...  

Objective: Endometriosis is a gynecological syndrome that affects many women around the world. The effective management for this illness has not been determined. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) and metformin on Bax/Bcl-2, Ki67, VEGF, TNF-α, and endometrial implants in endometriosis mice. Materials and Methods: Thirty mice with endometriosis were equally divided into 5 experimental groups (S1: 0.1 ml MSCs + 4 mg metformin; S2: 0.1 ml MSCs; S3: 4 mg metformin; S4: 0.1 ml NaCl 9%; and S5: 4 mg metformin + subsequent 0.1 ml MSCs) for 14 days. On the 15th day, peritoneal tissues of mice and endometrial implants were removed to examine the expressions of Bax/Bcl-2, Ki67, VEGF, and TNF-α using immunohistochemical staining, and Allred index and endometrial implants using image tracing method with a computer. The obtained data were analyzed using the Kruskal-Wallis and ANOVA tests, followed by the Least Significant Difference (LSD) and Mann-Whitney Post-hoc tests. Results: There were significant differences in the expressions of Bax/Bcl-2 (p=0.002), Ki67 (p=0.004), TNF-α (p=0.017), and endometrial implants (p=0.001) in all groups, except for VEGF (p=0.079). The values of S2 didn’t differ much compared to the control group (S4) in the Bax/Bcl-2 (p=0.487), TNF-α (p=0.191), and endometrial implants (p=0.2). S1 was found to have the highest Bax/Bcl-2 (1.67±0.845) and lowest TNF-α (4.67±2.15) and endometrial implant (0.86±2.11). Conclusion: MSCs alone had not any beneficial effect on the treatment of endometriosis, whereas metformin by itself exhibited favorable results. The combination of MSCs and metformin at the same time shows superior outcomes.


2021 ◽  
Vol 9 (A) ◽  
pp. 1195-1202
Author(s):  
Ezra Endria Gunadi ◽  
Yan Wisnu Prajoko ◽  
Agung Putra

BACKGROUND: Mesenchymal stem cells (MSCs) and bovine colostrum are potential therapies for the treatment of various degenerative and immune diseases. AIM: This study aimed to analyze the effect of MSCs on levels of tumor necrosis factor-Α (TNF-α) and macrophages M2 in the liver fibrosis of Wistar rats after 50% resection. METHODS: This study is a quasi-experimental post-test-only control group design to analyze the effect of giving bovine colostrum and MSCs to test animals on the process of regeneration of the remaining 50% liver with fibrosis. The study was conducted at the Stem Cell and Cancer Research Universitas Sultan Agung. The number of samples used was 40 male Wistar rats. The independent variables included MSC 1.000.0000 cells and bovine colostrum at a dose of 15 μL/g. Dependent variables used were macrophages M2 and levels of TNF-α ELISA. RESULTS: TNF-α levels on day 3 were (p = 0.001), day 7 were (p = 0.01), and day 10 were (p = 0.01) in liver tissue in various study groups analyzed using ELISA on day three*. The results showed differences which were significant between the control and treatment groups (p < 0.05). The expression of CD163 marked brown in liver tissue had more expression than the control group. CONCLUSION: The combination of MSCs and bovine colostrum can reduce TNF-α levels and significantly increase macrophages expression in the liver fibrosis of Wistar rats after 50% resection on the 3th, 7th, and 10th days.


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