scholarly journals Intrasplenic Transplantation of Bioencapsulated Mesenchymal Stem Cells Improves the Recovery Rates of 90% Partial Hepatectomized Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zun Chang Liu ◽  
Thomas Ming Swi Chang

Mesenchymal stem cells (MSCs) derived from bone marrow can secrete cytokines and growth factors and can transdifferentiate into liver cells. We transplanted polymeric membrane bioencapsulated MSCs into the spleens of 90% partial hepatectomized rats. This resulted in 91.6% recovery rates. This is compared to a recovery rate of 21.4% in the 90% hepatectomized rats and 25% in the 90% hepatectomized rats receiving intrasplenic transplantation of free MSCs. After 14 days, the remnant livers in the bioencapsulated MSCs group are not significantly different in weight when compared to the sham control group. From day 1 to day 3 after surgery, in the bioencapsulated MSCs group, the plasma HGF and IL-6 were significantly higher than those in the free MSCs group and control group (P<0.01); plasma TNF-αwas significantly lower (P<0.001). We concluded that the intrasplenic transplantation of bioencapsulated MSCs significantly increases the recovery rates of 90% hepatectomized rats. It is likely that the initial effect is from proliver regeneration factors followed later by the transdifferentiated hepatocyte-like cells. However, histopathological analysis and hepatocyte proliferation study will be needed to better understand the regenerative mechanisms of this result. This study has implications in improving the survival and recovery of patients with very severe liver failure due to hepatitis, trauma, or extensive surgical resection.

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 (7) ◽  
pp. 1327-1332
Author(s):  
Long Zhou ◽  
Kui Wang ◽  
Meixia Liu ◽  
Wen Wei ◽  
Liu Liu ◽  
...  

NF-κB activation and its abnormal expression are involved in the progression of glioma. miRNA plays a crucial role in bone diseases. The role of NF-κB is becoming more and more important. The purpose of this study is to explore the mechanism by how miR-1 regulates NF-κB signaling. C57 glioma mouse models were divided into osteoporosis (OP) group and control group. qPCR was used to measure miR-1 levels in OP and control mice. Bone marrow mesenchymal stem cells (BMSCs) were cultured and transfected with miR-1 specific siRNA to establish miR-1 knockout cell model followed by analysis of cell apoptosis, expression of NF-κB signaling molecules by western blot. qPCR results showed that miR-1 levels in OP mice were significantly reduced compared to control mice. A large number of siRNA particles were observed in transfected BMSCs under a fluorescence microscope. qPCR results showed that siRNA transfection significantly suppressed miR-1, indicating successful transfection. Flow cytometry revealed significant differences in cell apoptosis between miR-1 siRNA group and the NC group. Western blot indicated miR-1 promoted BMSCs differentiation via NF-κB mediated up-regulation of ALP activity. The expression of miR-1 is low in BMSCs of mice with glioma. In addition, BMSCs differentiation is enhanced by NF-κB activation via up-regulating miR-1.


2021 ◽  
Author(s):  
Vitoria Pimentel da Silva ◽  
Laura Provenzi ◽  
Nicole Becker ◽  
Giovani Zocche ◽  
Gabriel Leal ◽  
...  

Introduction: Temporal Lobe Epilepsy (TLE) is a disorder caused by neuronal electrical imbalance, clinically manifested by spontaneous and recurrent seizures1,2. Its pathogenesis involves channelopathies of calcium channels, which contributes to hyperexcitability and hypersynchrony in TLE3 . About 30% of patients do not respond to drug treatment4 , making it necessary to develop new therapeutic alternatives, such as cell therapy. This work aimed to evaluate the modulation of mesenchymal stem cells (MSCs) in the calcium channel CACNA1G (Cav3.1) gene expression. Methods: MSCs were extracted from Wistar rats bone marrow and then cultured and transplanted intravenously and intranasally in the control and epileptic groups. The brain was collected 1 and 7 days after transplantation to analyze gene expression. Results: The analysis showed that treated animals had greater gene expression, compared to animals not treated in the epileptic and control group, in both days and administration routes. Furthermore, epileptic animals that were not treated had a low or negative expression of the gene. The epileptic rats that were treated, on the other hand, had a marked increase in gene expression e in the prefrontal cortex. Conclusion: This up-regulation noted on the treated groups raises the hypothesis that MSCs would be using these channels to modify the microenvironment5 , intensifying Cav.3.1 transcription and contributing to tissue regeneration by neurodifferentiation6,7. This is supported by the increase in the calcium influx present in the early stages of neuronal maturation8,9. Thus, MSCs can modulate gene expression in the pilocarpine-induced animal’s brain, making Cav3.1 a target to be explored in epilepsy.


2020 ◽  
Author(s):  
Shujun Lin ◽  
Wenshan Lin ◽  
Chunling Liao ◽  
Tianbiao Zhou

Abstract Background: Renal damage caused by drug toxicity is becoming more and more common in clinic. How to avoid and treat kidney damage caused by drug toxicity is essential to maintain patient health and reduce social economic burden. In this study, we performed a meta-analysis to assess the nephroprotective effect of mesenchymal stem cells (MSCs) in therapy of kidney disease induced by toxicant. Methods: Cochrane Library, Embase, ISI Web of Science and PubMed databases were searched up to Dec 31, 2019 to identify the studies and extract the data to assess the efficacy of MSCs for kidney disease induced by toxicant using Cochrane Review Manager Version 5.3. 27 studies were eligible and recruited for this meta-analysis. Results: The results showed that the difference of Scr between MSCs treatment group and control group was notable for 2 days, 4 days, 5 days, 6-8 days, 10-15 days, ≥42 days (2 days: WMD =-0.88, 95%CI: -1.34, -0.42, P=0.0002; 4 days: WMD=-0.69, 95%CI: -0.99, -0.39, P<0.00001; 5 days: WMD=-0.46, 95%CI: -0.67, -0.25, P<0.0001; 6-8 days: WMD=-0.51, 95%CI: -0.79, -0.22, P=0.0005; 10-15 days: WMD =-0.38, 95%CI: -0.56, -0.20, P<0.0001; ≥42 days: WMD =-0.22, 95%CI: -0.39, -0.06, P=0.007). Furthermore, the difference of BUN between MSCs treatment group and control group was notable for 2-3 days, 4-5 days, 6-8 days, ≥28 days. The results also indicated that MSCs treatment can alleviate the inflammatory cells, necrotic tubule, regenerative tubules, renal interstitial fibrosis in kidney disease induced by toxicant. Conclusion: MSCs might be a promising therapeutic agent for kidney disease induced by toxicant.


2020 ◽  
Vol 32 (2) ◽  
pp. 238
Author(s):  
R. Singh ◽  
S. Saini ◽  
S. Ansari ◽  
S. Jamwal ◽  
D. Malakar

The present study was carried out to isolate mesenchymal stem cells (MSCs) from adipose tissue of cattle (Bos indicus), characterise them, and apply them for the treatment of mastitis and metritis in the cow. Cattle MSCs were isolated from adipose tissue near the loin region of cow. Isolated adipose tissue was subjected to enzymatic digestion using 2% collagenase with agitation at regular intervals. The cells obtained after digestion were resuspended in cell culture flasks containing growth enriched medium and cultured under standard culture conditions. Alkaline phosphatase staining was used as one of the parameters to confirm cultured putative MSCs. Bovine Ad-MSCs were further characterised using real time-PCR by amplification of MSC-specific markers: CD73, CD90, and CD105 as positive markers and CD34, CD45, and CD79a as negative markers. Immunocytochemistry showed the presence of CD73, CD90, and CD105 on the cell surface. Three groups-control (C), local (L), and intravenous (IV)-with 6 cows suffering from mastitis were taken in each group and subjected to MSC transplantation through local and intravenous routes. Control group animals were subjected to antibiotic treatment only. Similarly, another three groups were taken with 6 cows in each group suffering from metritis. Post-transplantation wound healing, tissue repair, and reduction in inflammation were monitored for 26 days, at different time intervals; that is, after Days 1, 3, 7, and 15. Blood samples were also collected from animals at the same time intervals for real time-PCR. A similar examination was also done in metritis groups along with the analysis of the reduction in turbidity of cervical fluid at the abovementioned time intervals. Real time-PCR was performed to determine relative expression of genes for proliferative factors, anti-inflammatory cytokines, and antimicrobial peptides on cells isolated from blood collected at different time intervals. Gene expression in the local group of mastitis subjected to MSC injection was significantly higher than that of the IV and control group. The somatic cell count declined in both local and IV groups compared with the control group. Whereas the expression of the same genes in the IV group of metritis was significantly higher than that of the local and control groups of cows. The turbidity of cervical fluid and mucus was reduced in the IV group compared with the local group. In conclusion, we demonstrated the healing potential of MSCs in a cow model via MSC injection. Promising results were obtained in curing mastitis in both local and IV groups, whereas healing in the case of metritis was significantly higher in the IV group compared with both the control and local groups of cows. The study indicates the potential use of MSc for treatment of mastitis and metritis in cattle through wound healing and decreasing microbial infection.


2020 ◽  
Author(s):  
Tianbiao Zhou ◽  
Shujun Lin ◽  
Chunling Liao ◽  
Wenshan Lin ◽  
Hongzhen Zhong

Abstract Background Renal damage caused by drug toxicity is becoming more and more common in clinic. How to avoid and treat kidney damage caused by drug toxicity is essential to maintain patient health and reduce social economic burden. In this study, we performed a meta-analysis to assess the nephroprotective effect of mesenchymal stem cells (MSCs) in therapy of kidney disease induced by toxicant. Methods Cochrane Library, Embase, ISI Web of Science and PubMed databases were searched up to Dec 31, 2019 to identify the studies and extract the data to assess the efficacy of MSCs for kidney disease induced by toxicant using Cochrane Review Manager Version 5.3. Results 27 studies were eligible and recruited for this meta-analysis. The results showed that the difference of Scr between MSCs treatment group and control group was notable for 2 days, 4 days, 5 days, 6-8 days, 10-15 days, ≥42 days (2 days: WMD =-0.88, 95%CI: -1.34, -0.42, P=0.0002; 4 days: WMD=-0.69, 95%CI: -0.99, -0.39, P<0.00001; 5 days: WMD=-0.46, 95%CI: -0.67, -0.25, P<0.0001; 6-8 days: WMD=-0.51, 95%CI: -0.79, -0.22, P=0.0005; 10-15 days: WMD =-0.38, 95%CI: -0.56, -0.20, P<0.0001; ≥42 days: WMD =-0.22, 95%CI: -0.39, -0.06, P=0.007). Furthermore, the difference of BUN between MSCs treatment group and control group was notable for 2-3 days, 4-5 days, 6-8 days, ≥28 days. The results also indicated that MSCs treatment can alleviate the inflammatory cells, necrotic tubule, regenerative tubules, renal interstitial fibrosis in kidney disease induced by toxicant. Conclusion: MSCs might be a promising therapeutic agent for kidney disease induced by toxicant.


2020 ◽  
Author(s):  
Tianbiao Zhou ◽  
Shujun Lin ◽  
Chunling Liao ◽  
Wenshan Lin ◽  
Hongzhen Zhong

Abstract Background Renal damage caused by drug toxicity is becoming more and more common in clinic. How to avoid and treat kidney damage caused by drug toxicity is essential to maintain patient health and reduce social economic burden. In this study, we performed a meta-analysis to assess the nephroprotective effect of mesenchymal stem cells (MSCs) in therapy of kidney disease induced by toxicant. Methods Cochrane Library, Embase, ISI Web of Science and PubMed databases were searched up to Dec 31, 2019 to identify the studies and extract the data to assess the efficacy of MSCs for kidney disease induced by toxicant using Cochrane Review Manager Version 5.3. Results 27 studies were eligible and recruited for this meta-analysis. The results showed that the difference of Scr between MSCs treatment group and control group was notable for 2 days, 4 days, 5 days, 6–8 days, 10–15 days, ≥ 42 days (2 days: WMD =-0.88, 95%CI: -1.34, -0.42, P = 0.0002; 4 days: WMD=-0.69, 95%CI: -0.99, -0.39, P < 0.00001; 5 days: WMD=-0.46, 95%CI: -0.67, -0.25, P < 0.0001; 6–8 days: WMD=-0.51, 95%CI: -0.79, -0.22, P = 0.0005; 10–15 days: WMD =-0.38, 95%CI: -0.56, -0.20, P < 0.0001; ≥42 days: WMD =-0.22, 95%CI: -0.39, -0.06, P = 0.007). Furthermore, the difference of BUN between MSCs treatment group and control group was notable for 2–3 days, 4–5 days, 6–8 days, ≥ 28 days. The results also indicated that MSCs treatment can alleviate the inflammatory cells, necrotic tubule, regenerative tubules, renal interstitial fibrosis in kidney disease induced by toxicant. Conclusion MSCs might be a promising therapeutic agent for kidney disease induced by toxicant.


2007 ◽  
Vol 334-335 ◽  
pp. 1201-1204 ◽  
Author(s):  
Chan Wai Chan ◽  
Ling Qin ◽  
K.M. Lee ◽  
H.Y. Yeung ◽  
Yun Yu Hu ◽  
...  

Grafting of autologous iliac crest and decortication approach in posterior spinal fusion surgery has been the “gold standard”. However, the limited source of autograft has prompted extensive research into bone substitute and biological enhancement of the fusion mass. In this study, the application of stem cell therapy by tissue engineering method was investigated to enhance posterior spinal fusion with -tricalcium phosphate ceramics in rabbit model. Rabbit bone marrow derived mesenchymal stem cells were aspirated from trochanter region of proximal femur. The mesenchymal stem cells were grown and directed to differentiate into osteogenic cells by osteogenic supplement (ascorbic acid, -glycerophosphate and dexamethasone) in basal medium (10% FBS in DMEM). The osteogenic cells were seeded on tricalcium phosphate ceramics for one day (MSC group, n=6). The cell-ceramics composite was implanted onto autologous L5 and L6 transverse processes with decortication approach in posterior spinal fusion. The cell free ceramics acts as control (Control group, n=6) and iliac crest autograft as positive control (Autograft group). The spinal segments were harvested at week 7 post-operation. Manual palpation was performed with spinal segments to assess any movement of L5-L6 vertebral joint. The stiffness of the joint was considered as solid fusion. The specimens then were fixed by formalin and transferred to 70% ethanol. The BMC and volume of fusion transverse processes of L5 and L6 was measured by peripheral quantitative computed tomography. In manual palpation, 50% solid fusion was found in MSC group, 60% in autograft group but none in control group. Moreover, the BMC of L5 and L6 transverse processes in MSC group was greater than autograft and control group (45%, 40% respectively, p<0.01). The volume of transverse processes in MSC group was greater than autograft by 45% (p<0.01) and control group by 26% (p<0.05). In conclusion, the mesenchymal stem cells derived osteogenic cells augmented spinal fusion and bone mineralization.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jiahua Shao ◽  
Jun Zhu ◽  
Yi Chen ◽  
Qiwei Fu ◽  
Lexiang Li ◽  
...  

Objective. To evaluate the effect of Kartogenin-pretreated exosomes derived from infrapatellar fat pad mesenchymal stem cells on chondrocyte in vitro and articular cartilage regeneration in vivo. Methods. Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were isolated from rabbits to harvest exosomes. After identification of mesenchymal stem cells and exosomes, rabbit chondrocytes were divided into three groups for further treatment: the EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells), KGN-EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN), and control group. After processing and proliferation, phenotypic changes of chondrocytes were measured. In the in vivo study, 4 groups of rabbits with articular cartilage injury were treated with KGN-EXO, EXO, IPFP-MSCs, and control. Macroscopic evaluation and histological evaluation were made to figure out the different effects of the 4 groups on cartilage regeneration in vivo. Results. The proliferation rate of chondrocytes in the EXO or KGN-EXO group was significantly higher than that in the control group ( P < 0.05 ). The qRT-PCR results showed that the expression of Sox-9, Aggrecan, and Col II was the highest in the KGN-EXO group compared with the EXO group and the control group ( P < 0.05 ). The results of Western blot were consistent with the results of qRT-PCR. In vivo, the cartilage defects in the KGN-EXO group showed better gross appearance and improved histological score than those in IPFP-MSC groups, EXO groups, and control groups ( P < 0.05 ). At 12 weeks, the defect site in the KGN-EXO group was almost completely repaired with a flat and smooth surface, while a large amount of hyaline cartilage-like structures and no obvious cracks were observed. Conclusion. Our study demonstrates that the exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN have potent ability to induce chondrogenic differentiation of stem cells, effectively promoting the proliferation and the expression of chondrogenic proteins and genes of chondrocytes. The KGN-EXO can also promote the repair of articular cartilage defects more effectively, which can be used as a potential therapeutic method in the future.


2018 ◽  
Vol 10 (2) ◽  
pp. 171-8 ◽  
Author(s):  
Ahmad Mozafar ◽  
Davood Mehrabani ◽  
Akbar Vahdati ◽  
Ebrahim Hosseini ◽  
Mohsen Forouzanfar

BACKGROUND: Stem cell-based therapy is one of the newest and evolving techniques in reproductive medicine. The aim of this study was to investigate the effect of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) transplantation on the testis of busulfan induced azoospermia in Balb/C mice.METHODS: Eighteen adult Balb/C mice were divided into three equal groups including control, busulfan and busulfan+cell therapy (busul+CT). For induction of azoospermia, busulfan and busul+CT groups received two injections of 10 mg/Kg of busulfan intraperitoneally with 21 days interval. In the cell therapy group 35 days after the last injection of busulfan, cluster of differentiation (CD)90+/CD34-/CD45- BM-MSCs were injected into the efferent duct of testis. Eight weeks after the BM-MSCs therapy, mice were sacrificed and tissues were taken for histological and histomorphometric evaluations.RESULTS: In busul+CT group, cellular and total diameters and cellular and cross-sectional areas significantly increased in comparison to busulfan group (p˂0.001), but there were no significant differences between busul+CT and control group (p˃0.05). Numerical density and tubular count per area unit in busul+CT and control groups were significantly less than busulfan group (p˂0.001), but there were no significant difference between busul+CT and control group (p˃0.05). The luminal diameter and area showed no significant change in all groups (p˃0.05). In busul+CT group, spermatogenesis index significantly increased when compared to busulfan and control groups (p˂0.001 and p˂0.05, respectively).CONCLOSION: Histomorphometric findings showed CD90+/CD34-/CD45- BM-MSCs transplantation on the testis of busulfan-induced azoospermic in Balb/C mice recovered spermatogenesis.KEYWORDS: mesenchymal stem cell, cell therapy, azoospermia, busulfan, mouse


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