Human Olfactory Mesenchymal Stem Cells Are a Novel Candidate for Neurological Autoimmune Disease

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.

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Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽

10.1371/journal.pone.0247662 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247662

Author(s):

Jingjing He ◽

Desheng Kong ◽

Zhifen Yang ◽

Ruiyun Guo ◽

Asiamah Ernest Amponsah ◽

...

Keyword(s):

Diabetes Mellitus ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Random Effects ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Significant Difference

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.

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Nephroprotective Effect of Mesenchymal Stem Cells in Therapy of Kidney Disease Induced by Toxicant

10.21203/rs.3.rs-60475/v1 ◽

2020 ◽

Author(s):

Shujun Lin ◽

Wenshan Lin ◽

Chunling Liao ◽

Tianbiao Zhou

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Kidney Disease ◽

Drug Toxicity ◽

Meta Analysis ◽

Control Group ◽

The Difference ◽

And Control ◽

Nephroprotective Effect

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.

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IDO and CD40 May Be Key Molecules for Immunomodulatory Capacity of the Primed Tonsil-Derived Mesenchymal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22115772 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5772

Author(s):

Hyun-Joo Lee ◽

Harry Jung ◽

Dong-Kyu Kim

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Cd4 T Cells ◽

Immune Cell ◽

Suppressive Effect ◽

Tnf Α ◽

Immunomodulatory Capacity ◽

Ifn Γ

Background: Tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have suppressive effect on T cells, yet much remains unknown about the underlying mechanisms supporting this effect. We investigated the underlying mechanism of the immunomodulatory effect of T-MSCs on immune cell proliferation and cytokine production. Methods: We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. Additionally, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. Results: T-MSCs significantly inhibited the immune cell proliferation and cytokine expression (TNF-α and IFN-γ) in the direct co-culture, but there was no suppressive effect in indirect co-culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co-expression CD40. Moreover, immune cells or CD4+ T cells showed lower TNF-α, IFN-γ, and IL-4 expression when the primed T-MSC were added; whereas those findings were reversed when the inhibitor for IDO (not IL-4) or CD40 were added. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4+ T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. Conclusions: Primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via Th1-mediated and Th2-mediated immune response.

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Histomorphology of Pancreatic Islet in Physiological Aging Female Rats Post Intravenous Human Wharton’s Jelly Mesenchymal Stem Cell Injection

Journal of Stem Cell Research and Tissue Engineering ◽

10.20473/jscrte.v3i1.16324 ◽

2019 ◽

Vol 3 (1) ◽

Author(s):

Wining Astini

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Pancreatic Islet ◽

Aging Treatment ◽

Wharton’S Jelly ◽

Female Rats ◽

Control Group ◽

Female Rat ◽

Wharton's Jelly

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.

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Nephroprotective effect of mesenchymal stem cells in therapy of kidney disease induced by toxicant

10.21203/rs.3.rs-21880/v1 ◽

2020 ◽

Author(s):

Tianbiao Zhou ◽

Shujun Lin ◽

Chunling Liao ◽

Wenshan Lin ◽

Hongzhen Zhong

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Kidney Disease ◽

Drug Toxicity ◽

Meta Analysis ◽

Control Group ◽

The Difference ◽

And Control ◽

Nephroprotective Effect

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.

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Nephroprotective effect of mesenchymal stem cells in therapy of kidney disease induced by toxicant

10.21203/rs.3.rs-25964/v1 ◽

2020 ◽

Author(s):

Tianbiao Zhou ◽

Shujun Lin ◽

Chunling Liao ◽

Wenshan Lin ◽

Hongzhen Zhong

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Kidney Disease ◽

Drug Toxicity ◽

Meta Analysis ◽

Control Group ◽

The Difference ◽

And Control ◽

Nephroprotective Effect

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.

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The Effect of Bone Marrow Mesenchymal Stem Cells (BMSCs) on Brain Injury Repair and Synapse Regeneration in Mice Under Different Conditions of Intrauterine Ischemia and Hypoxia Through Wnt Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2922 ◽

2022 ◽

Vol 12 (3) ◽

pp. 634-640

Author(s):

Changtao Fu ◽

Youdong Zhou ◽

Lei Wang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Brain Damage ◽

Control Group ◽

Hypoxic Injury ◽

Injury Group ◽

Group 6 ◽

Marrow Mesenchymal Stem Cells

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.

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Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells

Blood ◽

10.1182/blood-2004-09-3696 ◽

2005 ◽

Vol 105 (7) ◽

pp. 2821-2827 ◽

Cited By ~ 736

Author(s):

Sarah Glennie ◽

Inês Soeiro ◽

Peter J. Dyson ◽

Eric W.-F. Lam ◽

Francesco Dazzi

Keyword(s):

Stem Cells ◽

T Cells ◽

Mesenchymal Stem Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Interleukin 2 ◽

Cell Subset ◽

Activation Markers ◽

Ifn Γ

AbstractIt has been shown that mesenchymal stem cells (MSCs) induce T cells to become unresponsive. We characterized the phenotype of these T cells by dissecting the effect of MSCs on T-cell activation, proliferation, and effector function. For this purpose, an in vitro murine model was used in which T-cell responses were generated against the male HY minor histocompatibility antigen. In the presence of MSCs, the expression of early activation markers CD25 and CD69 was unaffected but interferon-γ (IFN-γ) production was reduced. The inhibitory effect of MSCs was directed mainly at the level of cell proliferation. Analysis of the cell cycle showed that T cells, stimulated in the presence of MSCs, were arrested at the G1 phase. At the molecular level, cyclin D2 expression was profoundly inhibited, whereas p27kip1 was up-regulated. When MSCs were removed from the cultures and restimulated with the cognate peptide, T cells produced IFN-γ but failed to proliferate. The addition of exogenous interleukin-2 (IL-2) did not restore proliferation. MSCs did not preferentially target any T-cell subset, and the inhibition was also extended to B cells. MSC-mediated inhibition induces an unresponsive T-cell profile that is fully consistent with that observed in division arrest anergy.

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Mesenchymal Stem Cells (MSC) Are Not Intrinsically Immune Privileged: Direct Demonstration in TCR Transgenic Mice and by Imaging of Allogeneic Luciferase+ MSC in Immune Competent Vs Immune Deficient Mice

Blood ◽

10.1182/blood.v112.11.549.549 ◽

2008 ◽

Vol 112 (11) ◽

pp. 549-549 ◽

Cited By ~ 1

Author(s):

Lior Zangi ◽

Andreas Beilhack ◽

Robert Negrin ◽

Raanan Margalit ◽

Yair Reisner

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Transgenic Mice ◽

Cd8 T Cells ◽

Immune Memory ◽

Control Group ◽

Allogeneic Bone ◽

Donor Type

Abstract Mesenchymal stem cells (MSC) can induce a broad array of immunomodulating mechanisms. Furthermore, several studies have advocated that MSC can be transplanted across allogeneic barriers without eliciting an immune response. This notion was based on clinical case reports or animal studies using highly sensitive techniques such as polymerase chain reaction, fluorescent in-situ hybridization or enhanced green fluorescent protein, enabling detection of rare cells in different tissues. However, a recent study comparing syngeneic and allogeneic MSC demonstrated that while the former cells induced tolerance to allogeneic bone marrow (BM) the use of donor type allogeneic MSC was counteractive leading to enhanced rejection of the BM cells. Thus it was indicated for the first time that allogeneic MSC might induce immune memory rather than tolerance to donor type cells. In the present study we directly addressed this possibility by infusing intravenously MSC isolated from H2db (C57BLxBalb) F1 donors, into TCR transgenic mice (the 2C model, C57BL/6 background), in which CD8+ T cells express a TCR transgene against H2d. Mice in the control group were infused with phosphate buffered saline (PBS). Thirty days after the first immunization, the mice were re-challenged with MSC and 5 days later peripheral blood CD8+ T cells were examined by FACS for the acquisition of a memory phenotype (CD122+, CD44+ and CD62Llow). This assay revealed a significantly elevated level of memory CD8 T cells (6.7±0.45 %) in the re-challenged mice compared to that found in the control group of naïve mice (0.4 ± 0.5 %, P<0.01). Further evidence for induction of immune memory by MSC was directly demonstrated by non-invasive imaging of bone marrow derived MSC isolated from Luciferase+ (Luc+) transgenic FVB-L2G85 mice (MSC-Luc+). Thus, while MSC (0.9–1.8 *108 MSC/Kg) infused intravenously or intraperitonealy into immune competent Balb/c mice survived longer (27% survival at 35 days) compared to adult fibroblast (Fib-Luc+ ) (9% survival at 15 days, p<0.01), this prolonged survival of MSC is significantly shorter compared to that exhibited in immune deficient Balb-Nude and NOD-SCID recipients (100% survival at 120 days, p<0.01), indicating that the MSC cannot evade immune rejection although capable of delaying it. The enhanced survival of MSC in Balb-Nude mice strongly indicates that rejection of these cells in normal Balb/c mice is mediated by T cells. Remarkably, rejection was found upon infusion of about 100- fold more MSC, compared to the cell number, which can currently be generated ex-vivo for transplantation in humans (around 1*106/Kg). Infusion of a lower number of MSC (4 *107 MSC/Kg) was found to be even less effective (9% survival at 15 days, p<0.01). To define whether the allogeneic rejection of MSC-Luc+ or Fib-Luc+ is associated with induction of immune memory, we re-challenged mice previously rejecting 2*106 Fib-Luc+ or MSC-Luc+ cells, with Fib-Luc+ cells. Thus, 30 days after rejection of the first inoculums the recipients were implanted with a second transplant of 2*106 Fib-Luc+ cells. Our data reveals that graft rejection was significantly more rapid in re-transplanted Balb/c mice. While a significant density of Fib-Luc+ cells can be detected in all transplanted recipients at day two, survival at day 5 was reduced to 27% or 18% in mice primed with Fib or MSC, respectively, compared to 81% in naive recipients (p<0.01). Survival of Fib-Luc+ cells in re-challenged mice was further reduced at day 9 (9% or 0% in mice previously receiving Fib or MSC, respectively) compared to 72% survival in naive recipients, p<0.01). Collectively, these results demonstrate that MSC are not intrinsically immune privileged and under allogeneic settings these cells induce rejection, which is followed by an immune memory. Considering that the use of allogeneic or even a third party (‘off the shelf’) MSC is commonly advocated for a variety of clinical applications, our results strongly suggest that long term survival of allogeneic MSC likely represents a major challenge. Further studies attempting to overcome rejection of donor MSC in the context of hematopoietic stem cell transplantation or in conjunction with co-stimulatory blockade are warranted.

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P0520EFFECT OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS ON SECONDARY ACUTE KIDNEY INJURY IN RATS WITH LIVER CIRRHOSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0520 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yan Mi

Keyword(s):

Stem Cells ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Olive Oil ◽

Umbilical Cord ◽

Kidney Injury ◽

Control Group ◽

Human Umbilical Cord ◽

Model Group

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 <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.

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