Clinical Evidence of Bone Marrow Therapy for Liver Failure

Autologous bone marrow stem cell therapy is currently used for many conditions. This is a great video, I wonder why not that many studies are done using this approach in kidney disease? I mean the results seem pretty clear and the worse think that happens is you have pain from the bone marrow aspiration process.

I think autologous MSCs from different sources (B.M , Adipose tissue ) or even umblical is the most promissing issue in cell theraby in general . I recommend other to increase number of clinical trials in different diseases

No i think that embryonic stem cells are the way to go. By embryonic stem cells we can:

1) kill innocent human life.

2) induce cancers in patients

3) spend a lot of money chasing the goal.

See adult stem cells are already used clinically, but this is not good since we dont know how they work. It is better to go backwards and use embryonic stem cells since they are more exciting and more patents can be filed.

Jonny there is no reason to be sarcastic. The only way to explain to people the power of adult stem cells is to talk about the positive successes that are published. Take a look on pubmed and find some clinical trials successes and then come back to this group and talk about them instead of writing meaningless sarcasm.

We know a lot about how stem cells work, but I do agree that we still are unsure exactly how fetal and embryonic cells will behave in the long term when administered to humans. There has been only one documented case of fetal cells causing benign tumor growth and that was in a child who received intrathecal fetal stem cells in 2001. His condition appeared only now.

Using new technology an embryo can survive after cells from the inner cell mass are aspirated. As a scientist I have a hard time believing a human life is taken with the destruction of an embryo that will end up in the bin anyway.

 Cord blood stem cells are available in abundance and I must admit that I do not understand why the debate on embryonics continues when cord cells could be used in clinical trials.

I think the issue is that it is very difficult for the field to deal with the concept of non-hematopoietic uses of cord blood. 

We published a paper describing some of the implications, both immunological and therapeutic of using cord blood in a non-hematopoietic manner.  The paper is available here https://www.translational-medicine.com/content/pdf/1479-5876-5-8.pdf

See cord blood can induces graft versus host disease post myeloablative therapy...thats why there is some hesitation to use it...alternatively the arguement has been made by some that in the context of an active recipient immune system, the allogeneic cord blood is rejected.

Studies such as the one demonstrating transfer of fetal cells into the mother and healing post stroke suggest that in certain situations the allogeneic cord blood cells may have beneficial effects.  Alternatively it may even be that the whole interaction between the cord blood and the allogeneic immune cells actually generates therapeutic cytokines.

The paper above is talking about autologous bone marrow, so this should not be an issue.  In fact there are many many trials ongoing with bone marrow.  Below is a list for cardiac alone...i just picked the first 10:

BACKGROUND: Serial cardiac magnetic resonance imaging (CMR) is the reference standard for evaluating left ventricular function, wall motion, and infarct size in patients with acute myocardial infarction, as well as remodeling during follow-up. The cardiac CMR substudy of the randomized multicenter REPAIR-AMI trial (Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study) aimed at gaining insight into postinfarction left ventricular remodeling processes. METHODS: Consecutive patients with ST-segment elevation myocardial infarction and primary percutaneous coronary intervention were enrolled (n = 204) and randomly assigned to either stem cell therapy (bone marrow-derived progenitor cells [BMC]) or placebo after bone marrow aspiration. In the magnetic resonance imaging substudy, 54 patients completed serial CMR (baseline, 4 and 12 months, respectively) after enrollment (27 BMC, 27 placebo). Image analysis was performed at a central core laboratory. RESULTS: There were no significant differences between the 2 groups with respect to global ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) at baseline. At 12 months, the treatment effect of BMC infusion on EF amounted to 2.8 absolute percentage points (P = .26), the progression of EDV at 12 months was less in the BMC group (treatment effect 14 mL, P = .12), and unlike placebo, ESV did not increase (absolute treatment effect 13 mL, P = .08), respectively. In patients with a baseline EF < median (EF < or = 48.9%), BMC administration was associated with a significantly improved EF (+6.6%, P = .01), reduced EDV increase (treatment effect 29.1 mL, P = .02), and abrogation of ESV increase (treatment effect 29.4 mL, P = .01) after 12 months, respectively. CONCLUSION: Intracoronary administration of BMC additionally improved left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction despite optimal "state-of-the-art" reperfusion and pharmacologic treatment on 1-year follow-up and beneficially interfered with adverse postinfarction left ventricular remodeling.

Myocardial regeneration therapy shows great promise as a treatment for heart failure. We recently introduced combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells as a treatment for human ischemic cardiomyopathy. We report the results of our first clinical trial of this technique, used to treat a patient with severe heart failure caused by ischemic cardiomyopathy who was being managed with a left ventricular assist system (LVAS). After combined cell transplantation, the patient showed signs of improved cardiac performance and angiogenesis, and reduced fibrosis.

BACKGROUND: Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches. METHODS: Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3-6 weeks or 3-4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy. RESULTS: A total of 60 patients were treated. The mean changes in infarct size at 3 months were -3.5 +/- 5.1% (95% CI -5.5% to -1.5%, P = 0.001) in the early group and -3.9 +/- 5.6% (95% CI -6.1% to -1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 +/- 5.6% (95% CI 1.3-5.6%, P = 0.003) and 3.4 +/- 7.0% (95% CI 0.7-6.1%, P = 0.017), respectively. At 9-12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 +/- 68.7 x 10(6) and 194.8 +/- 60.4 x 10(6) stem cells, respectively, were delivered to the myocardium, and 1.30 +/- 0.68 x 10(9) and 1.29 +/- 0.41 x 10(9) cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points. CONCLUSIONS: Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.

We carried out a pilot study on intracoronary transplantation of prenatal allogenic skeletal myoblasts and multipotent bone marrow stromal cells to patients with dilated cardiomyopathy. Intracoronary transplantation of allogenic cells is a feasible and safe procedure: there were no life-threatening rhythm and conduction disturbances, symptoms of hemodynamic instability, and thromboembolic complications. Positive clinical effect of cell transplantation persisted for 6 months and consisted in decreased content of brain natriuretic peptide and improved tolerance to physical exercises. We observed no reliable dynamics of the major echocardiographic parameters and their correlations with patient's status.

BACKGROUND: Experimental and clinical studies have suggested that intracoronary infusion of bone marrow-derived stem/progenitor cells (BMC) may improve left ventricular function after acute myocardial infarction (AMI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of BMC therapy on global left ventricular function in AMI. METHODS: A systematic literature search of MEDLINE, Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PUBMED from their inception to March 2007 was conducted using specific search terms. Reference lists of papers and reviews on the topic were further searched. Finally, six randomized controlled trials that comprised 517 patients were eligible for further meta-analysis. We used a standardized protocol to extract information on the included studies. RESULTS: Compared with the control groups, BMC therapy produced a slight improvement of the follow-up left ventricular ejection fraction (LVEF) [2.53%, 95% confidence interval (CI): 0.67-4.39, P=0.008] between 3 and 6 months. Similarly, BMC therapy also significantly improved the LVEF change from baseline to follow-up [2.88%, 95%CI: 1.69-4.08, P=0.000] compared to control groups, and the heterogeneity across the studies with regards to the follow-up LVEF (P=0.696) and the LVEF change (P=0.179). Major adverse cardiovascular events, including ventricular arrhythmia, rehospitalization for heart failure, and the composite of other cardiovascular events (cardiac death, recurrent myocardial infarction, infarct-vessel revascularization procedure, and stroke), were not significantly different between BMC therapy and control groups [relative risk (RR): 1.19, 95%CI: 0.68-2.06; RR: 1.79, 95%CI: 0.62-5.17; and RR: 1.05, 95%CI: 0.81-1.35, respectively]. CONCLUSION: On the basis of present evidence, intracoronary BMC infusion in patients with AMI seems to be safe and associated with slight improvement of the left ventricular ejection fraction at 3-6 months' follow-up.

AIMS: To provide systematic assessment of the safety and efficacy of autologous bone marrow-derived stem cell (BMSC) transplantation in acute myocardial infarction (AMI) based on clinical evidence. METHODS AND RESULTS: The search strategy included MEDLINE, EMBASE, the Cochrane Library, and Current Controlled Trials Register through to August 2007 for randomized controlled trials of BMSC treatment for AMI. Thirteen trials (14 comparisons) with a total of 811 participants were included. Data were analysed using a random effects model. Overall, stem cell therapy improved left ventricular ejection fraction (LVEF) by 2.99% [95% confidence interval (CI), 1.26-4.72%, P = 0.0007], significantly reduced left ventricular end-systolic volume (LVESV) by 4.74 mL (95% CI, -7.84 to -1.64 mL, P = 0.003), and myocardial lesion area by 3.51% (95% CI, -5.91 to -1.11%, P = 0.004) compared with controls. Subgroup analysis revealed that there was statistical significant difference in LEVF in favour of BMSCs when cells were infused within 7 days following AMI and when the BMSC dose administered was higher than 10(8) BMSCs. In addition, there were trends in favour of benefit for most clinical outcomes examined, although it should be acknowledged that the 95%CI included no significant difference. CONCLUSION: Stem cell treatment for AMI still holds promise. Clinically, these data suggest that improvement over conventional therapy can be achieved. Further, adequately powered trials using optimal dosing, longer term outcome assessments, more reliable, and more patient-centred outcomes are required.

OBJECTIVE: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. METHODS: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. RESULTS: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. CONCLUSIONS: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

Stem cell therapy for heart failure is a rapidly progressing field. The objective of this study was to assess the safety, and short-term results of thoracoscopic direct injection of angiogenic cell precursors into patients with endstage cardiomyopathy. Cells were obtained from the patient's own blood, avoiding immunological concerns. The number of cells prior to injection was 29.1 +/- 18.9 x10(6). Forty-one patients with cardiomyopathy (mean age, 58.5 +/- 14.3 years) underwent stem cell injection; 21 had dilated cardiomyopathy and 20 had ischemic cardiomyopathy. Overall ejection fraction improved significantly by 4.8% +/- 7.5% at 149 +/- 98 days postoperatively. It increased from 25.9% +/- 8.6% to 28.7% +/- 9.8% in dilated cardiomyopathy, and from 26.6% +/- 5.8% to 33.6% +/- 7.8% in ischemic cardiomyopathy. New York Heart Association functional class was significantly better at 2 months in both groups. It was concluded that thoracoscopic intramyocardial angiogenic cell precursor injection is feasible and safe in patients with cardiomyopathy. The early results are good, and phase II trials are in progress.

Stem cell treatment for acute or chronic ischemic myocardium has gained major attention in the last decade. Experimental and clinical studies have shown evidence for functional improvement after cell-based treatments in acute or chronically ischemic jeopardized myocardium. Since 2001 we have performed bone marrow-derived CD133+ stem cell transplantations with concomitant coronary artery bypass surgery. Although our focus is mainly on the functional results of the stem cell treatment, possible long-term side effects of the new therapeutic strategy should also be addressed. Here we present for the first time the long-term follow-up safety results of the Rostock trial after direct intramyocardial stem cell treatment in 32 patients.

Bone marrow (BM) cells may interact with coronary endothelium and modulate coronary atherosclerosis. We investigated the time course of coronary luminal loss and changes in conductance after intracoronary injection of enriched hematopoietic BM stem cells in patients with previous myocardial infarction (MI). Among 24 patients with acute MI, 13 were randomized to early (<7 days) and 11 to late (4 months) intracoronary injection of CD133+ cells after the infarction. Segmental quantitative coronary angiography and fractional flow reserve (FFR) measurements of the infarct-related (IR) artery (A) and contralateral artery (control) were performed. In the early group, at 4 months, cumulative luminal loss (LL) of the minimal luminal diameter (MLD) of the IRA distal to the stented segment was -0.39 (-0.51-0.10) mm (p < 0.05 vs. control). There was no further change in LL between 4 and 8 months [-0.09 (-0.26-0.15) mm]. In parallel, FFR decreased at 4 months [-0.16 (-0.26-0.001), p < 0.05 vs. control] but slightly increased from 4 to 8 months follow-up [+0.05 (-0.10-0.09)]. In the late group, LL of the MLD of the IRA distal to the stented segments was -0.12 (-0.47-0.07) mm (NS vs. control) at 4 months and further -0.07 (-0.25-0.05) mm (NS) between 4 and 8 months. At 8 months, the total LL of the MLD in the early and late group was only slightly higher compared to control [-0.34 (-0.48--0.16), -0.36 (-0.69--0.09), and -0.12 (-0.39-0.05) mm, respectively, NS]. Early intracoronary administration of hematopoietic BM stem cells in patients with previous MI is associated with accelerated luminal loss and reduced conductance of the infarct-related artery.