Bone Marrow Mononuclear Stem Cells Research Articles

Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally. This review offers a detailed analysis of stem cell applications in stroke (ischemic and hemorrhagic) recovery. It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), and Granulocyte-Colony Stimulating Factor (G-CSF) based stem cells, focusing on cell types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear Stem Cells (BMMSCs), and Neural Stem/Progenitor Cells (NSCs). The paper compiles clinical trial data to evaluate their effectiveness and safety and addresses the ethical concerns of these innovative treatments. By explaining the mechanisms of stem cell-induced neurological repair, this review underscores stem cells' potential in revolutionizing stroke rehabilitation and suggests avenues for future research.

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.

This issue of ACTA

This issue of ACTA

Theory and Applications of the (Cardio) Genomic Fabric Approach to Post-Ischemic and Hypoxia-Induced Heart Failure.

The genomic fabric paradigm (GFP) characterizes the transcriptome topology by the transcripts’ abundances, the variability of the expression profile, and the inter-coordination of gene expressions in each pathophysiological condition. The expression variability analysis provides an indirect estimate of the cell capability to limit the stochastic fluctuations of the expression levels of key genes, while the expression coordination analysis determines the gene networks in functional pathways. This report illustrates the theoretical bases and the mathematical framework of the GFP with applications to our microarray data from mouse models of post ischemic, and constant and intermittent hypoxia-induced heart failures. GFP analyses revealed the myocardium priorities in keeping the expression of key genes within narrow intervals, determined the statistically significant gene interlinkages, and identified the gene master regulators in the mouse heart left ventricle under normal and ischemic conditions. We quantified the expression regulation, alteration of the expression control, and remodeling of the gene networks caused by the oxygen deprivation and determined the efficacy of the bone marrow mono-nuclear stem cell injections to restore the normal transcriptome. Through the comprehensive assessment of the transcriptome, GFP would pave the way towards the development of personalized gene therapy of cardiac diseases.

TREATMENT OF A CHRONIC OBSTRUCTIVE PULMONARY DISEASE CASE WITH REGENTIME® PROCEDURE

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with high morbidity and mortality rates. It is characterized by airway and parenchymal inflammation leading to airway narrowing, decreased lung recoil, and eventual airflow limitation. Despite the advance in therapeutic approaches, no curative clinical treatment for COPD exists. We present the case of a 74-year-old gentleman diagnosed with COPD who underwent stem cell therapy with the Regentime® Procedure. This technique uses Autologous Bone Marrow -Mononuclear Stem Cells (BM-MSCs) which are partially differentiated and specifically redirected to the desired organ. Clinical follow-up 5 years after transplantation showed a decrease in major symptoms, including dyspnea, cough, fatigue, and decreased oxygen requirement. However, regression was registered during the past 2 years during which the patient’s oxygen requirement increased for optimal oxygen saturation. The results obtained support stem cell-based therapy as a promising therapeutic option for patients suffering from COPD. KEYWORDS: Regentime® Procedure, Bone Marrow-Mesenchymal Stem Cells, Chronic Obstructive Pulmonary Disease.

Intravitreal and subretinal syngeneic bone marrow mononuclear stem cell transplantation improves photoreceptor survival but does not ameliorate retinal function in two rat models of retinal degeneration.

To study and compare effects of syngeneic bone marrow mononuclear stem cells (BM-MNCs) transplants on inherited retinal degeneration in two animal models with different etiologies: the RCS and the P23H-1 rats. To compare the safety and efficacy of two methods of intraocular delivery: subretinal and/or intravitreal. A suspension of BM-MNCs was injected subretinally or intravitreally in the left eyes of P23H-1 and RCS rats at post-natal day (P) 21. At different survival intervals after the injection: 7, 15, 30 or 60 days, the retinas were cross-sectioned, and photoreceptor survival and glial cell responses were investigated using immunodetection of cones (anti-cone arrestin), synaptic connections (anti-bassoon), microglia (anti-Iba-1), astrocytes and Müller cells (anti-GFAP). Electroretinographic function was also assessed longitudinally. Intravitreal injections (IVIs) or subretinal injections (SRIs) of BM-MNCs did not produce adverse effects. The transplanted cells survived for up to 15 days but did not penetrate the retina. Both IVIs and SRIs increased photoreceptor survival, decreased synaptic degeneration and glial fibrillary acidic protein (GFAP) expression in Müller cells but did not modify microglial cell activation and migration or the electroretinographic responses. Intravitreal and subretinal syngeneic BM-MNCs transplantation decreases photoreceptor degeneration and shows anti-gliotic effects on Müller cells but does not ameliorate retinal function. Moreover, syngeneic BM-MNCs transplants are more effective than the xenotransplants of these cells. BM-MNC transplantation has potential therapeutic effects that merit further investigation.

Therapeutic Effects of Stem Cells for the Treatment of Diabetes Mellitus

Stem cell therapy may be the key to diabetes mellitus. In this study, we systematically retrieved the related studies and conducted this meta-analysis to evaluate the efficacy and safety of stem cell therapy for patients with diabetes mellitus. A systematic articles search was performed for eligible studies published up to April 28, 2021 through the PubMed, Cochrane library, ClinicalTrials.gov and Chinese National Knowledge Infrastructure database. The included articles were screened by using rigorous inclusion and exclusion criteria. All analyses were conducted using Review Manager 5.4. The quality of studies and risk of bias were evaluated. A total of 9 randomized controlled trials were included with a sample size of 326 subjects diagnosed with diabetes mellitus. Stem cells therapy was superior to placebo group in all of outcomes including hemoglobin A1c (mean deviation -0.51, 95 % confidence interval 0.70 to −0.32, p<0.00001), fasting plasma glucose (mean deviation -6.64, 95 % confidence interval -11.58 to -1.71, p=0.008), C-peptide (mean deviation 0.03, 95 % confidence interval 0.02 to 0.04, p<0.00001) and the requirement for insulin (mean deviation -10.34, 95 % confidence interval -16 to -4.67, p<0.00003). There was no significant difference in reported adverse events between stem cell therapy groups and placebo groups (Relative risk 1.77, 95 % confidence interval 0.89 to 3.51, p=0.10). Our results support stem cell therapy is a safe and effective therapeutic modality for diabetes mellitus. The best therapeutic outcome was achieved with bone marrow-mononuclear stem cells and hyperbaric oxygen therapy for type 2 diabetes mellitus, while the poorest outcome was observed with autologous bone marrowmesenchymal stromal cells for type 2 diabetes mellitus.

The efficacy of bone marrow mononuclear stem cell transplantation in patients with non-ischemic dilated cardiomyopathy-a meta analysis.

Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow mononuclear stem cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane’s risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18–23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected cells, and the type of injected cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow mononuclear stem cell therapy leads to significantly increased LVEF (MD = 4.54%, 95% CI [3.52, 5.56], P < 0.0001). Patients in the transplant group experienced less left ventricular end-diastolic diameter (millimeter) than the control arm (MD = −1.86 mm, 95% CI [−4.01, 0.29], P = 0.09). Additionally, Patients in the transplant group could walk 28.53 m more than the controls (MD = 28.53 m, 95% CI [2.51, 54.55], P = 0.03). Transplantation of bone marrow stem cells yields acceptable results regarding left ventricular ejection fraction and lowers the left ventricular end-diastolic diameter. Additionally, the six minutes walking test is improved in the transplant group.

Potential of Combination of Bone Marrow Nucleated and Mesenchymal Stem Cells in Complete Spinal Cord Injury.

Cell-based therapies represent one of the definitive treatment approaches to SCI which, to become a routine clinical application, is marred by several known unknowns. The Bone Marrow Mononuclear Cells (BMMNCs) and Mesenchymal Stem Cells (MSCs) represent the most clinically applied cell types for SCI in humans, with safety established, and to an extent, efficacy reported. In this review, we have analysed the clinical studies performed using BMMNC and MSC for complete SCI separately, and the potential for applying those cells in combination. We have also analysed those factors whose outcome in animal studies of SCI could be evaluated in depth but the clinical outcome cannot be evaluated intrinsically owing to practical difficulties. A combination of these two cell types, BMMNC and MSC, has been proven to be advantageous than applying them separately. Therefore, a thorough evaluation including the rationale and potential implications of applying these two therapies has been presented here, and we hypothesize that such a combination is likely to improvise the outcome of a wholesome approach to spinal cord regeneration after SCI.

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.

Breakthroughs in Preclinical Development of Ataluren (PTC124) As Therapeutic Option for Patients Affected By Shwachman-Diamond Syndrome: Towards the First Clinical Trial

Shwachman-Diamond syndrome (SDS) is one of the more common inherited bone marrow failure syndromes (IBMFS). Almost 90% of patients with SDS present mutations in the Shwachman-Bodian-Diamond syndrome gene (SBDS) which encodes for the homonymous small protein involved in ribogenesis. SDS is a multiple-organ disease mostly characterized by exocrine pancreas insufficiency, bone malformations, and more importantly bone marrow failure. Most patients with SDS present severe neutropenia, whereas thrombocytopenia and anemia are less frequent. Furthermore, 15-20% of patients develop myelodysplastic syndrome with high risk of acute myeloid leukemia (AML). STAT3 pathway is upregulated both in primary SDS leukocytes and immortalized B cells. Being STAT3 a key regulator of interleukin-6 (IL-6), we postulated that STAT3 hyper-activation could lead to a dysregulation of the IL-6 signaling cascade. Increased levels of IL-6 have been found in pediatric patients with AML and it has been associated with poorer outcomes in these patients, highlighting IL-6 as a cytokine potentially involved in the development of AML. Thus, our hypothesis is that STAT3-IL6 axis may contribute to leukemogenesis in SDS. Almost 55% of patients with SDS carry a specific nonsense mutations, namely the c.183-184TA&amp;gt;CT, which cause a premature termination codon (PTC). Ataluren (PTC124, PTC Therapeutics Inc, NJ) is a small PTC suppressor molecule already approved by the European Medicines Agency as a therapeutic option for Duchenne muscular dystrophy. Interestingly, we recently reported that ataluren can restore SBDS expression in bone marrow progenitors and in peripheral blood mononuclear cells isolated from patients with SDS. Moreover, we have shown that ataluren can reduce mTOR hyper-phosphorylation and excessive apoptotic rate observed in SDS leukocytes. More importantly, we reported that ataluren can improve myeloid differentiation in a small cohort of patients (Bezzerri et al, Am J Hematol 2018). In this further analysis considering an enlarged cohort of 20 SDS patients carrying nonsense mutations we found the following: Ataluren can significantly improve both myeloid colony-forming unit-granulocyte/macrophage (CFU-GM) and colony-forming unit granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM) generation from bone marrow mononuclear stem cells obtained from an enlarged cohort of 20 patients with SDS carrying nonsense mutations. Ataluren indeed almost doubled the number of CFU-GM and CFU-GEMM after 7 and 14 days of treatment.Colony-forming unit erythroid (CFU-E) generation was not affected by the treatment.Ataluren induces neutrophil maturation in SDS bone marrow mononuclear stem cells (mean increase of 61% CD16+ CD11b+ cells over untreated controls) after 24-48 hours of treatment.Consistently with STAT3 hyper-activation observed in SDS cells, here we show that patients with SDS present a significantly increased level of IL-6 in plasma (4.3-fold higher expression than the healthy control group). Also lymphoblastoid cell lines (LCL) and primary bone marrow mesenchymal stromal cells (MSC) obtained from patients with SDS show increased IL-6 release in culture supernatants compared to healthy controls (2.5-fold and 6.8-fold higher levels, respectively).Of note, ataluren can reduce IL-6 expression in SDS cells restoring normal levels both in LCL and MSC. In conclusion, these new data support the enrollment of patients for the first clinical trial for this drug in SDS. Furthermore, this study could pave the way for the use of ataluren for other nonsense mutation-mediated IBMFS where STAT3-IL6 axis and similar pro-leukemic pathways are involved. Disclosures Bezzerri: Marco Cipolli, Valentino Bezzerri, Baroukh Maurice Assael: Patents &amp; Royalties: WO2018/050706 A1 "Method of treatment of Shwachman-Diamond syndrome". Cipolli:Marco Cipolli, Valentino Bezzerri, Baroukh Maurice Assael: Patents &amp; Royalties: WO2018/050706 A1 "Method of treatment of Shwachman-Diamond syndrome".

Gene therapy for refractory angina and cell therapy for heart failure: experience of a Brazilian research group.

Cell therapy has shown impressive effects in experimental cardiomyopathy models. To a lesser extent, gene therapy has also been studied. In both cases, translation to clinical therapy has been disappointing. This paper is intended to describe the experience and achievements of a multicenter working group located in Porto Alegre, southern Brazil, in experimental and translational research projects for cell-based and gene therapy methods in the treatment of dilated and ischemic cardiomyopathies. The results of preclinical and clinical studies showed that bone marrow mononuclear stem cells indeed have an effect in improving myocardial perfusion and contractile function, but the overall results are poorly translated to the clinical level. Gene therapy studies with direct myocardial injections of naked VEGF 165 plasmid showed improvement in myocardial perfusion and function in animal models. A randomized clinical trial found that this method is safe and improved myocardial perfusion, but the benefits disappeared after 1 year. An animal experiment associating VEGF 165 with angiopoietin was undertaken in mini pigs to extend the durability of that therapy. In conclusion, our efforts to better understand the mechanisms and functions of gene and cell-based therapies in cardiology resulted in significant findings and propose a future look at cell-free therapeutic approaches.

Bone marrow mononuclear cells versus mesenchymal stem cells from adipose tissue on bone healing in an Old World primate: can this be extrapolated to humans?

ABSTRACT In veterinary medicine, the cell therapy is still unexplored and there are many unanswered questions that researchers tend to extrapolate to humans in an attempt to treat certain injuries. Investigating this subject in nonhuman primates turns out to be an unparalleled opportunity to better understand the dynamics of stem cells against some diseases. Thus, we aimed to compare the efficiency of bone marrow mononuclear cells (BMMCs) and mesenchymal stem cells (MSCs) from adipose tissue of Chlorocebus aethiops in induced bone injury. Ten animals were used, male adults subjected, to bone injury the iliac crests. The MSCs were isolated by and cultured. In an autologous manner, the BMMCs were infused in the right iliac crest, and MSCs from adipose tissue in the left iliac crest. After 4.8 months, the right iliac crests fully reconstructed, while left iliac crest continued to have obvious bone defects for up to 5.8 months after cell infusion. The best option for treatment of injuries with bone tissue loss in old world primates is to use autologous MSCs from adipose tissue, suggesting we can extrapolate the results to humans, since there is phylogenetic proximity between species.

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.

Stem cell registry programme for patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting: what benefits does it derive?

AimsStandardization of stem cell therapy requires application of appropriate methods to evaluate safety and efficacy, including long‐term pharmacovigilance. To accomplish this objective, a long‐term registry programme was installed.Methods and resultsWe analysed 150 patients with ischemic cardiomyopathy, who received intramyocardial CD133+ bone marrow mononuclear stem cell treatment combined with coronary artery bypass grafting (CABG) or CABG alone. The mortality rate, major adverse cerebral and cardiac events, and functional outcome parameters were evaluated for the time period up to 14 years follow‐up. As a result, we have stratified the patient population (96 patients) into responders and non‐responders. Furthermore, the analysis of relevant predictors of good response to CD133+ bone marrow mononuclear stem cell treatment was performed. Several positive tendencies related to stem cells transplantation were demonstrated. First, no significant difference in major adverse cardiovascular and cerebral events was observed between stem cell and control group up to 14 years follow‐up. Second, an improvement of left ventricle ejection fraction (LVEF) in stem cell group retained for 5 years in contrast with CABG‐only group, where no significant changes in LVEF after 2 years were observed. In addition, LVEF under 30% and left ventricle end diastolic diameter above 60 mm were independent predictors of functional response to CD133+ cell therapy.ConclusionsParticipants with overt heart failure benefit most from CABG combined with intramyocardial injection of CD133+ bone marrow mononuclear cell within the group. An improvement LVEF in stem cell group remained for 5 years in contrast with the CABG‐only group. The patients, in whom the improvement of both LVEF and LVED was observed, have benefited by increased life expectancy.