Autologous Bone Marrow Mononuclear Stem Research Articles

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker

BackgroundType 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. MethodsA pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). ResultsThe primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60′ (p = 0.07) and 90′ (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. ConclusionIntraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

Коррекция гепатоцеллюлярной недостаточности путем внутрипортального введения мононуклеарных клеток аутологичного костного мозга при циррозе печени: опыт ГБУЗ ГКБ им. С.П. Боткина ДЗМ

Hepatic failure is one of the most common manifestation of liver cirrhosis. Currently, there are no medication or invasive procedure, which can reliably improve liver function. Research on the use of autologous bone marrow mononuclear stem cells to correct the morphofunctional manifestations of acute and chronic liver failure is encouraging. This clinical case demonstrates the safety and clinical effectiveness of intraportal administration of autologous bone marrow mononuclear cells obtained by apheresis after stimulation with granulocyte-macrophage colony-stimulating factor.

Autologous bone-marrow mononuclear stem cell therapy in patients with stroke: a meta-analysis of comparative studies

BackgroundThere is a need to promote recovery after stroke with novel therapeutic interventions. Of them, bone-marrow mononuclear cell (BM-MNC) therapy offers promising outcomes in preclinical and clinical models.AimsTo investigate the efficacy and safety of BM-MNCs versus traditional medical care of stroke patients.Summary of reviewA meta-analysis was conducted involving controlled prospective studies and randomized clinical trials (RCTs) which investigated the changes in the scores of neurological functions (the National Institutes of Health Stroke Scale [NIHSS]), the indices of functional recovery (the Barthel Index [BI] and the modified Rankin scale [mRS]) at 3 and 6 month post-transplantation. A total of nine studies (five RCTs) recruited 469 stroke patients (65.5% males, 49.25% received the intervention). There were no significant differences in NIHSS, BI, or mRS scores after 3 months of follow-up. However, the BI indices of BM-MNCs-receiving patients improved significantly after 6 months (standardized mean difference = 1.17, 95% confidence interval, 0.23 to 2.10, P = 0.01) as compared to traditional treatment. The risk of mortality and adverse events and the proportion of patients with favorable outcomes (mRS ≤ 3) were similar in both groups.ConclusionBoth the BM-MNCs and medical stroke treatment have similar outcomes in terms of safety and short-term efficacy, while the effect of therapy is significant only after 6 months. More well-designed, large sized RCTs are needed to confirm the efficacy of stem cell therapy over long periods of follow-up.

The Effectiveness of Selective Stem Cell Placement on Gait Performance in Patients with Multiple Sclerosis: a Phase I Clinical Trial

This report describes a Phase I clinical trial of a novel selective stem cell placement (SSCP) protocol using autologous bone marrow mononuclear stem cells (BM-MNSCs) to treat patients with multiple sclerosis (MS) with post-operative functional changes measured by gait performance. Previous studies have demonstrated that clinically significant gait deviations occur at all stages of MS that involve walking. Consequently, to determine the functional benefit of SSCP, the timed 25-foot walk (T25FW) was administered to 31 MS patients before and after treatment. The time and number of steps taken to complete the test significantly decreased post-intervention. This suggests that recovery of function in MS patients is possible and that SSCP using BM-MNSCs should be considered for future clinical trials as a possible treatment for MS. Study limitations and directions for future research are also discussed.

A Study of Intracoronary Injection of Hematopoietic Stem Cells in Pediatric Dilated Cardiomyopathy: Is It an Applicable Solution for Critically Ill Patients?

Background: Benefits of stem cell therapy on remodelling and cardiac function have been described in adults with dilated cardiomyopathy and acute myocardial infarction. Objectives: We investigated the effect of this treatment modality amongst children with severe dilated cardiomyopathy. Methods: Intracoronary injection of autologous bone marrow mononuclear stem cells was performed in our centers for 8 severely ill children during 2015 - 2016. The mean age of the patients was 10.1 years (5 girls, 3 boys). They were followed by longitudinal speckle tracking echocardiography (STE) and conventional echocardiography for 6 months. Results: Heart functional class improved in 62% of patients. M-mode echocardiography showed significant improvement in ejection fraction (mean 24.8 ± 8.3 vs. 37.4 ± 10.5) and in STE, the mean global longitudinal strain improved (GLS: -2.8 ± 1.9 vs. -5.2 ± 3.9). None of the patients had serious complications. Conclusions: Intracoronary injection of autologous mononuclear stem cells might improve the ventricular function and cardiac remodelling in pediatric patients with dilated cardiomyopathy and could be considered in critically ill patients.

181 Therapeutic Application of Autologous Bone Marrow Mononuclear Stem Cell in Complete Spinal Cord Injury in Human

181 Therapeutic Application of Autologous Bone Marrow Mononuclear Stem Cell in Complete Spinal Cord Injury in Human

Effect of direct intramyocardial autologous stem cell grafting in the sub-acute phase after myocardial infarction.

To assess the efficacy and safety of intramyocardial autologous bone marrow mononuclear stem cells (BMMNC) grafting combined with coronary artery bypass grafting (CABG) on ventricular remodeling and global and regional wall motion after acute transmural myocardial infarction (AMI). Randomized controlled trial including 20 patients with non-revascularized transmural AMI, left ventricular ejection fraction (LVEF) lower than 50% and surgical indication for CABG. The stem cell group was treated with BMMNC grafting by direct intramyocardial injection between the 10th and 15th days after AMI (subacute phase) combined with CABG under cardiopulmonary bypass; the control group was only treated with CABG. Magnetic resonance imaging with gadolinium and stress echocardiography were performed presurgery and 9 months postsurgery. Seventeen patients completed the follow-up. The baseline characteristics of both groups were homogeneous. No significant differences were found in the increase in LVEF (control: 6.99±4.60, cells: 7.47±6.61, P=0.876) or in the decrease in global (control: 0.28±0.39, cells: 0.22±0.28, P=0.759) or regional (control: 0.52±0.38, cells: 0.74±0.60, P=0.415) wall motion indices between the control and stem cell groups of AMI patients. No differences were found in the recovered non-viable segments (control: 1.29±1.11, cells: 2.50±1.41, P=0.091) or in the decrease in end-diastolic (control: 14.05±19.72, cells: 18.40±29.89, P=0.725) or end-systolic (control: 15.42±13.93, cells: 23.06±25.03, P=0.442) volumes. No complications from stem cell grafting were observed. The results from our study reported herein suggest that intramyocardial BMMNC administration during CABG in patients with AMI causes no medium- to long-term improvement in ventricular remodeling.

Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial

BackgroundStem cell therapy has emerged as a promising method for improving motor function of patients with cerebral palsy. The aim of this study is to assess the safety and effectiveness of autologous bone marrow mononuclear stem cell transplantation in patients with cerebral palsy related to oxygen deprivation.MethodsAn open label uncontrolled clinical trial was carried out at Vinmec International Hospital. The intervention consisted of two administrations of stem cells, the first at baseline and the second 3 months later. Improvement was monitored at 3 months and 6 months after the first administration of stem cells, using the Gross Motor Function Measure (GMFM) and Modified Ashworth Score which measures muscle tone.ResultsNo severe complications were recorded during the study. After transplantation, 12 patients encountered fever without infections and 9 patients experienced vomiting which was easily managed with medications. Gross motor function was markedly improved 3 months or 6 months after stem cell transplantation than at baseline. The post-transplantation GMFM-88 total score, each of its domains and the GMFM-66 percentile were all significantly higher (p-value < 0.001). Muscle spasticity also reduced significantly after transplantation (p-value < 0.001). The therapy was equally effective regardless of sex, age and GMFCS level (p-value > 0.05).ConclusionAutologous bone marrow mononuclear cell transplantation appears to be a safe and effective therapy for patients with cerebral palsy.Trial registrationClinicalTrials.gov Identifier: NCT02569775. Retrospectively registered on October 15, 2015.

FUNCTIONAL AND SYMPTOMATIC IMPROVEMENT AFTER CELLULAR THERAPY IN A PEDIATRIC CASE OF CHRONIC TRAUMATIC INCOMPLETE SPINAL CORD INJURY

Spinal cord injury (SCI) in the pediatric population is a rare incidence and has devastating consequences. Cellular transplantation is one of the emerging strategies in the treatment of SCI. Here, we present a case report of an 8-year-old female who sustained traumatic incomplete SCI at the level of D10-D11 four years ago. Two years after the accident, she underwent 2 doses of cell transplantation with autologous bone marrow mononuclear stem cells (BMMNCs) administered intrathecally (injection into the sub-arachnoid space), followed by intensive neuro- rehabilitation. Over the span of 18 months’ post -cellular therapy, there was improvement in the functional status with FIM (Functional Independence Measure) score improving from 108 to 113. She improved in transfer mobility, static and dynamic balance in sitting and standing positions, ambulation and activities of daily living (ADLs). The bowel and bladder control improvement was significant. There was a shift from A to B on the American Spinal Injury Association (ASIA) scale. Spinal Cord Independence Measure (SCIM) score increased from 73 to 96 after the two cellular therapies. No adverse events related to the transplantation procedure were observed. This case is a “proof of concept study” based on the fact that transplantation of autologous bone marrow mononuclear cells along with rehabilitation may augment the recovery processes in patients with chronic traumatic spinal cord injuries. Further, randomized controlled clinical studies are warranted to prove it’s the therapeutic efficiency.

Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis

Stem cell therapy, an evolving, progressive field of therapeutics has shown several successes in areas where classic treatments failed to prevent or stop disability. Starting in 2009, twenty two sequential patients with progressive Multiple Sclerosis (MS) courses were treated with Autologous Bone Marrow Mononuclear stem cells (BM-MNSCs). The cells were given both intravenously and intrathecally. Using the Expanded Disability Status Scale (EDSS) score for evaluation, our data indicates that the majority of the patients benefited on the average one point on the scale. This paper adds to the body of evidence suggesting the safety and efficacy of autologous BM-MNSCs in the treatment of MS and awaits validation through larger, randomized studies.

Attenuation of Hindlimb Ischemia after Associated Autologous Transplantation of Bone Marrow Mononuclear Cells and Platelet Rich Plasma

Objective: The purpose of this study was to determine whether autologous bone marrow mononuclear stem cell (BMCs) associated with platelet rich plasma (PRP) transplantation improves peripheral collateralization in a rabbit ischemic limb model. Methods: Unilateral hindlimb ischemia was surgically induced in New Zealand White rabbits (n=30). A total of 106 BMCs+PRP were intramuscularly implanted into each ischemic limb. Blood flow was monitored by Doppler in the ischemic and control animals. Histological analysis of capillary density in the ischemic limbs was performed 30 days after the ischemia induction. Results: Histological sections of ischemic gastrocnemius muscle showed that capillary index (capillary/muscle fiber) was greater in the BMCs+PRP implantation group 30 days after the ischemia induction than in the saline group. Conclusion: This study demonstrated that implantation of BMCs+PRP into ischemic limbs effectively induces collateral vessel formation, suggesting that this cell therapy is useful as a novel strategy for therapeutic peripheral arterial disease.

Effect of intramyocardial delivery of autologous bone marrow mononuclear stem cells on the regional myocardial perfusion

The aim of the sub-study of the MYSTAR randomised trial was to analyse the changes in myocardial perfusion in NOGA-defined regions of interest (ROI) with intramyocardial injections of autologous bone marrow mononuclear cells (BM-MNC) using an elaborated transformation algorithm. Patients with recent first acute myocardial infarction (AMI) and left ventricular (LV) ejection fraction (EF) between 30-45% received BM-MNC by intramyocardial followed by intracoronary injection 68 +/- 34 days post-AMI (pooled data of MYSTAR). NOGA-guided endocardial mapping and 99m-Sestamibi-SPECT (single photon emission computer tomography) were performed at baseline and at three months follow-up (FUP). ROI was delineated as a best polygon by connecting of injection points of NOGA polar maps. ROIs were projected onto baseline and FUP polar maps of SPECT calculating the perfusion severity of ROI. Infarct size was decreased (from 27.2 +/- 10.7% to 24.1 +/- 11.5%, p<0.001), and global EF increased (from 38 +/- 6.1% to 41.5 +/- 8.4%, p<0.001) three months after BM-MNC delivery. Analysis of ROI resulted in a significant increase in unipolar voltage (index of myocardial viability) (from 7.9 +/- 3.0 mV to 9.9 +/- 2.7 mV at FUP, p<0.001) and local linear shortening (index of local wall motion disturbances) (from 11.0 +/- 3.9% to 12.7 +/- 3.4%, p=0.01). NOGA-guided analysis of the intramyocardially treated area revealed a significantly increased tracer uptake both at rest (from 56.7 +/- 16.1% to 62.9 +/- 14.2%, p=0.003) and at stress (from 59.3 +/- 14.2% to 62.3 +/- 14.9%, p=0.01). Patients exhibiting >or=5% improvement in perfusion defect severity received a significantly higher number of intramyocardial BM-MNC. In conclusion, combined cardiac BM-MNC delivery induces significant improvement in myocardial viability and perfusion in the intramyocardially injected area.

Efficiency of Intramyocardial Injections of Autologous Bone Marrow Mononuclear Stem Cells in Patients with Ischemic Heart Failure: Long-Term Results

Introduction: Intramyocardial injection of autologous bone marrow mononuclear cells (BMMC) is believed to be a promising method for the treatment of patients with chronic ischemic heart disease. Hypothesis: To evaluate long-term results of intramyocardial bone marrow cell injection in patients with severe ischemic heart failure. Methods: Ninety nine ischemic heart failure patients (age 58 ± 5) with left ventricle ejection fraction (LVEF) ≤35% and III-IV NYHA and CCS functional classes without possibility for conventional revascularization were randomized into two groups: 1 group (n=49) - received intramyocardial BMMC injection and patients of the second group (n=50) were treated with standard medical therapy for HF. The NOGA system was used to administer 4.9 x107 BMMC into the infarction border zone. We analyzed all clinical data at 6 and 12 month of the follow-up period. Results: None of the patients developed periprocedural complications following BMMC injections. In the first group, the injections led to improvement of CCS class (3.5 ± 0.5 vs 2.1 ± 0.6 after 6 months and 1.9 ± 0.6 after 12 months (p<0.05 vs. baseline) and NYHA functional class (3.4 ± 0.1 vs 2.3 ± 0.2 after 6 months and 2.0 ± 0.2 after 12 months; p<0.05). The same characteristics in patients of the 2 group therapy remained unaltered (p = NS). LVEF increased in group 1 (34 ± 2% vs 42 ± 3%; p<0.05) while it tended to decrease in the control group (34 ± 2% vs 31 ± 3%; p = NS). Summed rest score improved in the first group after 6 months (14.7 ± 5.4 vs 10.7 ± 4.9; p<0.05). The improvement of stress score was more noticeable (18.2 ± 5.4 vs 9.4 ± 4.2; p<0.05). Neither stress nor rest score changed in patients of the second group. At the moment after 12 month follow up period 5 patients (10.2%) from group 1 died compared with 14 patients (28%) from group 2 (log rank test, p=0.008). Conclusions: Intramyocardial injection of autologous bone marrow mononuclear cells in ischemic heart failure patients is a safe procedure that improves clinical symptoms and has beneficial effecton LV function.

Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction

Stem cell therapy can facilitate cardiac repair in infarcted myocardium, but the optimal cell type remains uncertain. We conducted a randomized, blind, and placebo-controlled comparison of autologous bone marrow mononuclear cell and mesenchymal stem cell therapy in a large-animal model of chronic myocardial infarction. Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of mononuclear cells (227.106 +/- 32.106 cells), mesenchymal stem cells (232.106 +/- 40.106 cells), or placebo (n = 8 per group). Cardiac performance and remodeling were assessed up to 16 weeks' follow-up. At echocardiographic analysis, the wall motion score index showed a sustained improvement after mononuclear cell transfer (from 1.8 +/- 0.1 to 1.5 +/- 0.07) and a moderate late improvement after mesenchymal stem cell transfer (from 1.9 +/- 0.08 to 1.7 +/- 0.1). After mononuclear cell transfer, end-systolic elastance increased (from 2.23 +/- 0.25 to 4.42 +/- 0.55 mm Hg/mL), infarct size decreased (from 13% +/- 0.67% to 10% +/- 1.17%), N-terminal B-type natriuretic propeptide level decreased (from 608 +/- 146 to 353 +/- 118 pmol/L), and relative wall area and arterial density increased. Vascular endothelial growth factor receptor 2 expression was upregulated in the border zone. No change in cardiac contractility or histologic parameters was noted in the mesenchymal stem cell group. In a canine model of chronic myocardial infarction, bone marrow mononuclear cell transfer is superior to mesenchymal stem cell transfer in improvement of cardiac contractility and regional systolic function and reduction in infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favorable angiogenic environment and neovascularization.