Autologous Bone Marrow-derived Cell Transplantation Research Articles

The relationship between myeloid-derived supressor cells and clinico-laboratory parameters in patients with liver cyrrosis

In the present study, we used multicolor flow cytometry assay to measure the numbers of various myeloid suppressor cell subpopulations (Lin-HLA-DR-CD33+, Lin-HLA-DR-CD33+CD66b+, and CD14+HLA-DRlow/-) in peripheral blood of 51 participants, including 33 patients with viral- and 1 8 patients with «nonviral» (alcoholic or biliary/autoimmune) liver cirrhosis. Patients in both groups had increased proportions of Lin-HLA-DR-CD33+, Lin-HLA-DR-CD33+CD66b+, and CD 14+HLA-DRlow/-cells which levels did not depend on the type and replication of the virus in viral liver cirrhosis. In viral liver cirrhosis, the relative numbers of Lin-HLA-DR-CD33+cells directly correlated with the albumin levels (Rs=0.45; p=0.029). In «nonviral» group an inverse relationship was found between these indicators (Rs = -0.56; p=0.02), in addition the proportion of Lin-HLA-DR-CD33+and CD14+HLA-DRlow/-cells directly correlated with disease severity scores (Child-Pugh and MELD) direct correlation of the proportion of Lin-HLA-DR-CD33+and CD14+HLA-DRlow/-cells with the disease severity scores (Child-Pugh and MELD). Comparison of the initial content of myeloid suppressors with the response to complex therapy (that included autologous bone marrow-derived cell transplantation), showed that in viral liver cirrhosis, the proportion of Lin-HLA-DR-CD33+cells was characterized by a prognostic significance and, at values

Effects of timing on intracoronary autologous bone marrow-derived cell transplantation in acute myocardial infarction: a meta-analysis of randomized controlled trials

BackgroundSeveral cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI).MethodsA systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy.ResultsThirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3–7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3–7 days after PCI reduced LV end-diastolic indexes (–4.48; 95% CI, −7.98 to –0.98; P = 0.01) and LV end-systolic indexes (–6.73; 95% CI, –11.27 to –2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = –3.29, 95% CI, –4.49 to –2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = –5.25, 95% CI, –9.30 to –1.20; P = 0.01), as well as in patients who received a dose of 10^7–10^8 cells (WMD = –12.99, 95% CI, –19.07 to –6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control.ConclusionsIn this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.

Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns?

BackgroundLiver stem cell therapy (SCT) has been suggested as a promising means to improve liver regeneration in advanced liver disease. However, data from trials are heterogeneous, with no systematic histological evaluation. The aim of this study is to specifically analyze the effect of autologous SCT on liver regeneration and on gene expression changes.MethodsIndividuals in the randomized controlled trial of SCT in alcoholic hepatitis with paired liver biopsies were included (n = 58). Immunohistochemistry (Ki67, K7, and CD68), in situ hybridization (SPINK1), and global gene expression analysis were performed on liver biopsies (30 control patients and 28 patients with transarterial administration of bone marrow-derived stem cells) both at baseline and after 4 weeks of follow-up.ResultsNo difference between the two groups could be observed regarding the proliferative hepatocyte number, proliferative K7-positive cells, or total K7-positive cells at the 4-week follow-up liver biopsy. However, patients who received SCT showed a more important liver macrophagic expansion as compared to standard treatment. Transcriptome data revealed changes in genes linked with inflammation (CD68 and SAA), regeneration (SPINK1 and HGF), fibrosis (COL1A1), and stem cells (CD45). No changes in gene pathways involved in liver growth and cell cycle proteins were evident. SPINK1 mRNA was present by in situ hybridization at week 4 in SCT patients in the liver parenchyma areas adjacent to macrophage recruitment and liver cell proliferation.ConclusionsThe analysis of liver tissue after SCT demonstrated an expansion of macrophages concurrent with an upregulated expression of genes involved in inflammatory and regenerative pathways. With the negative results from the clinical trial, the impact of the SCT has to be interpreted as weak, and it is not able to modify the clinical course of this severe liver disease.

Efficacy and safety of intracoronary autologous bone marrow-derived cell transplantation in patients with acute myocardial infarction: insights from randomized controlled trials with 12 or more months follow-up.

Until now there was no systematic review concerning the chronic effects of intracoronary bone marrow-derived cell (BMC) transplantation in patients with acute myocardial infarction (MI). Improvement of cardiac function in patients with acute MI post BMC transplantation might last longer than 12 months. We searched MEDLINE, EMBASE, and the Cochrane database through June 2009. Eligible studies were randomized controlled trials of intracoronary BMC transfer in acute MI patients with follow-up duration equal to or longer than 12 months. A total of 8 trials involving 725 participants were identified. Compared with controls, BMC transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.37% (95% confidence interval [CI]: 2.66%-6.08%; P < 0.00001), reduced left ventricular end-diastolic volume (LVEDV) by 5.71 mL (95% CI: 2.03-9.40 mL; P = 0.002), left ventricular end-systolic volume (LVESV) by 8.94 mL (95% CI: 4.22-13.66 mL; P = 0.0002), and infarct size by 2.42% (95% CI: 1.33%-3.51%, P < 0.00001). Bone marrow-derived cell treatment also significantly reduced the risk of death (relative risk [RR]: 0.33, 95% CI: 0.13-0.89; P = 0.03), while the risk of reinfarction was similar between the 2 groups (RR: 0.62, 95% CI: 0.09-4.12; P = 0.62). Subgroup analysis showed that the BMC transplantation-induced LVEF increase was more significant in patients age < 55 and with cells transferred 6 or 7 days after MI. Beneficial effects of intracoronary BMC transplantation could last more than 12 months in acute MI patients.

Autologous bone marrow-derived cell transplantation in the treatment of cerebral stroke

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Transplantation of Autologous Bone Marrow-Derived Cells into the Myocardium of Patients Undergoing Coronary Bypass

Animal studies suggest that cell transplantation, including bone marrow-derived cells, can ameliorate left ventricular remodeling following myocardial ischemia. Clinical evaluation of the potential benefits of this approach is limited by the lack of safety and feasibility studies. We have assessed the safety and feasibility of intramyocardial transplantation of autologous bone marrow-derived cells in patients undergoing coronary artery bypass graft (CABG) surgery. Between December 2001 and May 2002 7 patients, scheduled for CABG, consented to the trial. All had CABG using hypothermic cardiopulmonary bypass (CPB) and cold cardioplegic arrest. An average of 21 10(6) (8.6 10(6) to 35.1 10(6)) nucleated cells, and 4.2 10(4) (2.5 10(4) to 8.1 10(4)) CD34+ cells were injected into the anterior-lateral wall of the left ventricle, after discontinuation of cardiopulmonary bypass. The end points to assess safety included death, massive bleeding, electrocardiographic or biochemical evidence of myocardial infarction, ventricular dysrhythmia, myocardial perfusion, ventricular function, and the patients' functional status. All patients recovered well without ventricular arrhythmia, bleeding, or other major peri-operative complications. The average intensive care unit (ICU) and hospital stay was 1 and 7 days, respectively. Repeat Technetium-99m myocardial perfusion stress imaging and echocardiography 6 weeks after surgery showed improvement in tissue perfusion, and an average improvement of left ventricular function of 13.5% +/- 11.54% (the mean pre- and post-operative left ventricular EF were 32.5% +/- 15.46% and 46% +/- 18.55%, respectively). Twenty-four hours Holter monitoring showed no significant arrhythmia, 3 months post-operatively. All patients with narrow QRS complex showed no evidence of late potential, on signal-averaged electrocardiogram. At 4 to 9 months after surgery patients were in NYHA functional class "I". This early clinical experience shows that autologous bone marrow-derived cell transplantation into myocardium is feasible and relatively safe. Further clinical trials to assess the role of cell transplantation for myocardial repair are required.