scholarly journals Cord Lining Mesenchymal Stem Cells Have a Modest Positive Effect on Angiogenesis in Hindlimb Ischemia

Author(s):  
Kenon Chua ◽  
Fui Ping Lim ◽  
Victor Kwan Min Lee ◽  
Toan Thang Phan ◽  
Bee Choo Tai ◽  
...  

Purpose: We investigated the use of human Cord Lining Mesenchymal Stem Cells (CL-MSCs) (US Patent number 9,737,568), in a rabbit hindlimb ischemia model, and evaluated their potential in stimulating neovascularization. Allogenic human CL- MSCs could potentially be used to treat patients with lower limb ischemia and non-healing wounds.Methods: Twenty rabbits were divided into two separate groups. We created a hindlimb ischemia model surgically. At 21 and 49 days post-operatively, animals in the treatment group were injected with CL-MSCs (500,000 cells per 0.2 ml on each site) at 10 different sites (Quadriceps- 4 sites, Hamstrings- 4 sites and Calf-−2 sites) in the hindlimb muscles. The control group received only saline injection to the corresponding sites at the same time point as the treatment group. We then evaluated the effects of treatment on neovascularization by angiography, laser doppler perfusion imaging, as well as by histology. We evaluated the tissue samples for any signs of local immune reaction to the cell implantation. We also observed the rabbit clinically for any adverse effects after treatment.Results: We found a higher number of CD31 positive cells in the treatment group, with a greater number of capillaries found in the treated muscles. The Rectus Femoris demonstrated a median vessel count/muscle fiber of 0.121 for the treatment group, compared to 0.076 in the control group (median difference 0.04; 95% CI 0.001–0.11; p = 0.041). The Gastrocnemius demonstrated a median vessel count/muscle fiber of 0.175 for the treatment group, compared to 0.089 in the control group (median difference 0.087; 95% CI −0.006 to 0.234; p = 0.07). Blood perfusion quantification through Laser Doppler Perfusion Imaging (LDPI) also demonstrated a non-statistically significant increase in perfusion in favor of the treatment group. CL-MSCs demonstrated no toxicity associated morbidity and minimal local immune reaction to implantation.Conclusion: CL-MSCs have a positive effect on angiogenesis in a rabbit hindlimb ischemia model. This preliminary data is encouraging and paves the way for future large animal studies or for clinical trials.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.



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 ◽  
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.



Author(s):  
Wining Astini

The increasing population of aged people will have the important role in the life, but the function of their bodies will decrease because of aging. Aging will increase the risk of degenerative disease, one of example is diabetes. The disease is related to the aging in the pancreatic organ which progressively declines by age. The aimed of the experiment was to determine the effect of human wharton’s jelly mesenchymal stem cells by injecting intravenously in aging female rats. This study used 3 young female rats (3 months) and 6 aging female rats (24 months). The experiment consisted of three groups. The young control group (A), the aging control group (B) that received NaCl (0.9%) 0,4 mL, the aging treatment group (C) received 1 x 106 cells/kg of human wharton’s jelly mesenchymal stem cells 0,4 mL. The aging control and the aging treatment group were injected 4 times with the interval in 3 months. The end of the experiment (12 months), the rats were anesthetized and sacrificed. The pancreatic tissues were collected to examine the pancreatic islets by histology studies. Changes of the pancreatic islet in control and treated groups were examined using hematoxylin and eosin staining. These findings conclude that injecting human wharton’s jelly mesenchymal stem cell increase the diameter and total pancreatic islet in the treatment group. In other side, the cell population of pancreatic islet also have significant differences (P<0.05) in treated physiological aging female rat groups than control aging female rat group.



2022 ◽  
Vol 12 (3) ◽  
pp. 634-640
Author(s):  
Changtao Fu ◽  
Youdong Zhou ◽  
Lei Wang

Bone marrow mesenchymal stem cells (BMSCs) can be differentiated into a variety of cells and repair damaged cells. We explore whether BMSCs can repair brain damage and synapses regeneration in mice under intrauterine ischemia and hypoxia. Twenty-five pregnant mice were assigned into control group, 6% hypoxic injury group, 8% hypoxic injury group, 6% treatment group, 8% treatment group followed by analysis of the expression of MBP, MAG, CSPGs, IGF-1, NCAN, COLIV, SynD1G1, GFAP, GSK-3β, and β-actin by RT-PCR and Western blot. Our results showed that the expression of MBP, MAG, COL IV, SynD1G1, IGF-1 in the treatment group were significantly higher than those in hypoxic injury group with significant differences between the 8% treatment group and 6% treatment group (P < 0.05). In conclusion, BMSCs can repair brain damage and synapse regeneration in mice under different intrauterine ischemia and hypoxia conditions which might be through Wnt signaling pathway.



2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yan Mi

Abstract Background and Aims Acute kidney injury( AKI) is one of the most common complications of decompensated cirrhosis, and it primarily presents as a sharp decrease in glomerular filtration rate, rapid increase in serum creatinine( SCr) and urea nitrogen. And the search for specific and safe treatment has been a research hot spot in recent years. In this article, the effect of human umbilical cord mesenchymal stem cells on carbon tetrachloride (CCl4)-induced liver fibrosis (HF) in rats with acute kidney injury and the possible mechanism are investigated. Method Human umbilical cord blood mesenchymal stem cells were sub-cultured by adherent method, and the cells were identified by morphological observation, cell phenotypic analysis and multi-directional differentiation potential analysis methods. WASTA rats were randomly divided into control group, cirrhosis model group and treatment group, with 10 rats in each group. Model group and treatment group were injected with CCl4-olive oil (1:1) solution 3 mL·kg -1, and the control group was given the same amount of olive oil for intervention, twice a week for 8 weeks. Rats in treatment group were administrated wth Human umbilical cord mesenchymal stem cells (2 × 109 /L) via the tail vein at the 5th week after injection of CCl4-olive oil solution, but the other rats were injected with 0.9% normal saline, once a week for 6 weeks. After the intervention, Serum, kidneys and 24 hours urine of rats in each group were collected, which were applied for a detection of serum creatinine and urea nitrogen, malondialdehyde (MDA), NO content and superoxide dismutase (SOD), as well as renal pathological examination. Results 1.In vitro, umbilical cord blood mesenchymal stem cells was passaged to the third generation, and the morphology was uniform and spiraled. Phenotypic analysis showed that the positive rates of stem cell markers CD29, CD44 and CD105 were all greater than 95%, the positive rate of HLA-DR (graft-versus-host disease-associated factor) less than 10%, and the positive rate of CD34 and CD45 lower than 20% (Figure 1). 2. Compared with the cirrhotic model group, MDA content of serum and kidney in model group significantly decreased under the effect of mesenchymal stem cell (p &lt;0.01) (Table 1). 3. The normal group had normal liver tissue structure, ordered liver cells, no hepatic edema, and no lesions. In the model group, large-area lesions, including edema of liver cells, rupture of cell membranes, and infiltration of inflammatory cells, had appeared. Compared with the model group, Hepatocellular necrosis, edema, and inflammatory cell infiltration were significantly improved after transplanting Human umbilical cord mesenchymal stem cells (Figure 2). 4.In the model group, the rat renal tubules disappeared and the lumen was disordered. After injection of Human umbilical cord mesenchymal stem cells, renal tubular and renal interstitial damage is improved and the thickening of glomerular basement membrane is reduced (Figure 3). Conclusion In CCl4-induced liver cirrhosis model rats, human umbilical cord mesenchymal stem cells can protect the kidney by reducing free radicals and cellular lipid peroxidation in vivo.



2021 ◽  
Vol 12 ◽  
Author(s):  
Chongjun Xiao ◽  
Di Lu ◽  
Jinshuo Chen ◽  
Xiaoyan Chen ◽  
Huizhu Lin ◽  
...  

Background: Human olfactory mesenchymal stem cells (OMSC) have become a novel therapeutic option for immune disorder or demyelinating disease due to their immunomodulatory and regenerative potentials. However, the immunomodulatory effects of OMSC still need to be elucidated, and comparisons of the effects of different MSCs are also required in order to select an optimal cell source for further applications.Results: In animal experiments, we found neural functional recovery and delayed EAE attack in the OMSC treatment group. Compared with umbilical cord–derived mesenchymal stem cells (UMSC) treatment group and the control group, the OMSC treatment group had a better neurological improvement, lower serum levels of IFN-γ, and a lower proportion of CD4+IFN-γ+ T splenic lymphocyte. We also observed OMSC effectively suppressed CD4+IFN-γ+ T cell proportion in vitro when co-cultured with human peripheral blood–derived lymphocytes. The OMSC-mediated immunosuppressive effect on human CD4+IFN-γ+ T cells was attenuated by blocking cyclooxygenase activity.Conclusion: Our results suggest that OMSC treatment delayed the onset and promoted the neural functional recovery in the EAE mouse model possibly by suppressing CD4+IFN-γ+ T cells. OMSC transplantation might become an alternative therapeutic option for neurological autoimmune disease.



Author(s):  
I Gde Rurus Suryawan ◽  
Anudya Kartika Ratri ◽  
Andrianto Andrianto ◽  
Meity Ardiana ◽  
Ricardo Adrian Nugraha

Background. Polytetrafluoroethylene (PTFE) patch is commonly used during surgical closure for atrial septal defect (ASD) and/or ventricular septal defect (VSD). It has several limitations such as inability to grow, repair, and remodel. Aneurysm formation, thrombosis, and the inability of patches to grow or remodel are usual, especially in children and young adults. To tackle these limitations, we try to use fibronectin and human adipose-derived mesenchymal stem cells (hAMSCs) in PTFE patch. Objective. To understanding positive impact of fibronectin to enhance hAMSCs cell-to-cell adherence and cell-to-patch surface attachment into PTFE patch for future ASD or VSD closure. Methods. Cultured of hAMSCs cells were fixated with 15 mL methanol and CD90+, CD105+, CD45- antibodies were labeled FITC, rinsed with PBS and analyzed under fluorescence microscope for 15 minutes. Fibronectin solution 0.1% were used to soak patch scaffolds for approximately 2 hours duration, and then dried for 20 minutes for treatment group. As for control group, Fibronectin solution was not added on the culture. The samples were examined with scanning electron microscope (SEM). Results. SEM examination showed incomplete attachment of the cells even after 10 days on control group at 1.14 &plusmn;1.13 (Figure 2). In contrast, treatment group showed more cells attached to the patch surface at 31.25 &plusmn;13.28 (p 0.000) (Figure 3). Observation at 5 days was 17.67 &plusmn; 20.21, at 7 days was 12.11 &plusmn; 10.94, at 10 days was 18.83 &plusmn; 23.25. No significant statistical difference of mean cell per view among each treatment group (p 0.802). Conclusion. Fibronectin has a positive impact on hAMSCs attachment seeded onto PTFE patch. These properties, in combination with their developmental plasticity, have generated tremendous interest because of the potential use of hAMSCs in regenerative medicine to replace damaged tissues.



2020 ◽  
Author(s):  
Lei Shu ◽  
Changming Niu ◽  
Ruyou Li ◽  
Tingrong Huang ◽  
Yan Wang ◽  
...  

Abstract Background COVID-19 is a highly infectious respiratory disease. No effective therapeutics have yet been proved for treating of severe COVID-19. Objectives To determine whether human Umbilical Cord Mesenchymal Stem Cells infusion may be effectiveness and safety in the treatment of severe COVID-19. Methods The severe COVID-19 randomly divided into 2 groups, standard treatment group and standard treatment plus hUC-MSCs infusion group. The incidence of severe patients aggravated to critically illness, 28-day mortality, clinical symptoms improvement, time to clinical symptoms improvement, hematologic indicators including C-reaction protein, lymphocyte number, interleukin 6 and imaging changes were observed and compared between two groups. Measurements and Main Results The incidence of severe patients aggravated to critically illness and 28-day mortality were 0 in hUC-MSCs treatment group, while 4 patients in control group were deteriorated to critical illness and been used invasive ventilation, 3 of them died, and 28-day mortality was 10.34%. In hUC-MSCs treatment group, the time to clinical improvement was shorter, clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation had improved obviously began the third day of stem cells infusion, and reached the significant difference on the day 7, CRP and IL-6 were significantly decreased from day 3 of infusion, the time for lymphocyte count returned to normal range was significant faster, and lung inflammation absorption was significantly shorter from CT imaging. Conclusions Intravenous transplantation of hUC-MSCs is a safe and effective way that can be considered as salvage and priority choice in the treatment of severe COVID-19.



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