The objective of this study was to compare the impact of umbilical cord-derived mesenchymal stromal cell (UCMSC) transplantation on the motor functions of identical twins with cerebral palsy (CP) and to analyze the correlation between the efficacy and hereditary factors.

The role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial.

To study the clinical efficacy of traditional Chinese medicine (TCM) intervention "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") for treating liver failure due to chronic hepatitis B.

Optimal prevention of late cytomegalovirus (CMV) disease is poorly defined.

We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after myeloablative allogeneic hematopoietic cell transplantation (HCT). Patients received increasing doses of MAPC (1, 5, or 10 million cells per kilogram recipient weight) as a single i.v. dose on day +2 after HCT (n = 18), or once weekly for up to 5 doses (1 or 5 million cells per kilogram; n = 18). Infusional and regimen-related toxicities were assessed for 30 days after the last MAPC dose. Of 36 allogeneic HCT donors (17 related and 19 unrelated), 35 were 6/6 HLA matched. MAPC infusions were well tolerated without associated infusional toxicity, graft failure, or increased incidence of infection. Median times to neutrophil (n = 36) and platelet (n = 31) engraftment were 15 (range, 11 to 25) and 16 (range, 11 to 41) days, respectively. The overall cumulative incidences of grades II to IV and III and IV acute graft-versus-host disease (GVHD) at day 100 were 37% and 14%, respectively (n = 36). In the group that received the highest single MAPC dose (10 million cells/kg), day 100 incidence of grade II to IV GVHD was 11.1% (1 of 9) with no observed cases of grade III and IV GVHD. We found no evidence for MHC class II allogeneic antibody induction, although some patients showed an increase in serum anticlass I titers compared with baseline. MAPC contribution to blood chimerism was negligible. These phase I data support the safety of stromal stem cell therapy and suggest that MAPC should be tested prospectively as a novel therapeutic option for GVHD prophylaxis after HCT.

Knowledge gained from the field of tissue engineering, helped to develop a biological substitute that promotes tissue regeneration. The usual biological substitute consists of stem cells, growth factors and an appropriate scaffold. The present randomized controlled clinical and radiographic study was undertaken to evaluate the effectiveness of mesenchymal stem cells cultured on beta tricalcium phosphate (β-TCP) in combination with rh-PDGF-BB in treatment of infrabony defect in humans. A total of 24 infrabony defects in 14 systemically healthy patients were selected for the present study. The selected defects exhibited a probing pocket depth (PPD) of ≥ 5 mm and depth of infrabony component ≥ 3 mm as assessed by clinical and radiographic measurements and later confirmed by intrasurgical measurement. Baseline measurements included were Plaque Index (PI), Papillary Bleeding Index (PBI), Probing Pocket Depth (PPD), Relative gingival marginal level (RGML), Relative Clinical Attachment Level (R-CAL) and Radiographic Defect Depth (DD) and linear bone growth (LBG). 6 weeks after initial therapy, the defects were randomly assigned to either test group or control group. The control group was treated by an open flap debridement (OFD) only, while the test group was treated by a Stem cells cultured on β-TCP in combination with rh-PDGF-BB. All the measurements recorded preoperatively were repeated at 6 months after the surgery. The efficacy of each treatment modality was investigated through statistical analysis. Mean probing pocket depth reduction was significantly greater in test group (4.50 ± 1.08 mm) compared to the OFD group (3.50 ± 0.90 mm). Mean gains in clinical attachment level was 3.91 ± 1.37 mm in the test group and 2.08 ± 0.90 mm in the control group. The mean increase in gingival recession (GR) was less in test group (0.58 ± 0.79 mm) compared to OFD group (1.4 ± 0.66 mm). Radiographic defect depth reduction was greater in the test group (3.50 ± 0.67 mm) with 88.33% defect fill compared to control group (1.83 ± 0.38 mm) with only 52.77% defect fill. Linear bone growth (LBG) was significantly improved by 3.58 mm in test group, while in control group, it was 1.83 mm. Regenerative approach using Stem cells cultured on β-TCP in combination with rh-PDGF-BB for the treatment of human infrabony defects resulted in a significant added benefit in terms of CAL gains, PPD reductions greater radiographic defect fill and improvement in Linear bone growth (LBG) compared to the OFD alone.

Key modalities of integrative medicine known to rejuvenate the mind and body are meditation, yoga, and controlled diet. It has been shown previously that intensive or prolonged mind and body therapies (MBT) may have beneficial effects on the well-being of healthy people and in patients. Telomerase activity and levels of peripheral blood adult pluripotent stem cells (PB-APSC) are reliable markers of long-term well-being that are known to decrease with age. The objective of this study is to understand the effect of our MBT program on telomerase activity and stem cells in blood collected from the participants.

Kidney transplantation has improved survival and quality of life for patients with end-stage renal disease. Despite excellent short-term results due to better and more potent immunosuppressive drugs, long-term survival of transplanted kidneys has not improved accordingly in the last decades. Consequently there is a strong interest in immunosuppressive regimens that maintain efficacy for the prevention of rejection, whilst preserving renal structure and function. In this respect the infusion of mesenchymal stromal cells (MSCs) may be an interesting immune suppressive strategy. MSCs have immune suppressive properties and actively contribute to tissue repair. In experimental animal studies the combination of mammalian target of rapamycin (mTOR) inhibitor and MSCs was shown to attenuate allo immune responses and to promote allograft tolerance. The current study will test the hypothesis that MSC treatment, in combination with the mTOR inhibitor everolimus, facilitates tacrolimus withdrawal, reduces fibrosis and decreases the incidence of opportunistic infections compared to standard tacrolimus dose.

Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions.

Cell therapy is promising as an exploratory cardiovascular therapy. We have recently developed an investigational new drug named Stempeucel (bone marrow-derived allogeneic mesenchymal stromal cells) for patients with acute myocardial infarction (AMI) with ST-segment elevation. A phase I/II randomized, double-blind, single-dose study was conducted to assess the safety and efficacy of intravenous administration of Stempeucel versus placebo (multiple electrolytes injection).

Type 2 diabetes (T2D) is characterized by impaired vascular regeneration owing to reduced endothelial progenitor cells (EPCs). While statins are known to increase EPCs, the effects of statin withdrawal on EPCs are unknown. Herein, we evaluated the effects of statin discontinuation on EPCs, inflammation and in vivo angiogenesis. Thirty-four T2D patients were randomized to 5-day discontinuation or continuation of statin treatment. At baseline and at day 5, we determined lipid profile, EPC levels, monocyte-macrophage polarization, and concentrations of hsCRP, VEGF, SDF-1α, and G-CSF. Angiogenesis by human circulating cells was assessed in vivo. At day 5, patients who stopped statins showed raised total and LDL cholesterol and EPCs compared to baseline, while no changes were observed in patients who continued statins. No changes were observed in hsCRP, VEGF, SDF-1α, G-CSF, M1 and M2 macrophages and classical, intermediate and nonclassical monocytes in both groups. In vivo angiogenesis by circulating cells was increased in patients who stopped statin treatment. In vitro, cholesterol supplementation stimulated mobilizing signals in human bone marrow mesenchymal stem cells. In conclusion, a brief statin withdrawal increases circulating EPCs and functional proangiogenic cells in T2D. These findings identify statin-sensitive pathways as reverse target mechanisms to stimulate vascular repair in diabetes.

To compare the efficacy of dioctahedral smectite and iodine glycerin (DSIG) cream with topical mouth rinse (composed of saline, gentamicin and Vitamin B12) in treatment of chemotherapy induced oral mucositis (OM).

We investigated the effects of intracoronary transplantation of CD34(+) cells on myocardial perfusion in patients with nonischemic dilated cardiomyopathy (DCM).

Peripheral artery disease (PAD) is recognized as a public health issue because of its prevalence, functional limitations, and increased risk of systemic ischemic events. Current treatments for claudication, the primary symptom in patients with PAD, have limitations. Cells identified using cytosolic enzyme aldehyde dehydrogenase (ALDH) may benefit patients with severe PAD but has not been studied in patients with claudication. PACE is a randomized, double-blind, placebo-controlled clinical trial conducted by the Cardiovascular Cell Therapy Research Network to assess the safety and efficacy of autologous bone marrow-derived ALDH(br) cells delivered by direct intramuscular injections in 80 patients with symptom-limiting intermittent claudication. Eligible patients will have a significant stenosis or occlusion of infrainguinal arteries and a resting ankle-brachial index less than 0.90 and will be randomized 1:1 to cell or placebo treatment with a 1-year follow-up. The primary end points are the change in peak walking time and leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance imaging at 6 months compared with baseline. The latter 3 measurements are new physiologic lower extremity tissue perfusion and PAD imaging-based end points that may help to quantify the biologic and mechanistic effects of cell therapy. This trial will collect important mechanistic and clinical information on the safety and efficacy of ALDH(br) cells in patients with claudication and provide valuable insight into the utility of advanced magnetic resonance imaging end points.

Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study.

Circulating progenitor cells (CPC) are bone marrow-derived cells that are mobilized into the circulation. While exercise is a powerful mediator of hematopoiesis, CPC levels increase, and reports of their activation after different types of exercise are contradictory. Moreover, few studies have compared the possible effects of different training programs on CPC concentrations. 43 physically active healthy male subjects (age 22±2.4 years) were assigned to 4 different training groups: aerobic, resistance, mixed and control. Except for the control group, all participants trained for 6 weeks. Peripheral blood samples were collected through an antecubital vein, and CPC CD34(+) was analyzed on different days: pre-training, post-training, and 3 weeks after finishing the training period. While no significant differences in CPC were observed either within or between the different training groups, there was a tendency towards higher values post-training and large intra- and intergroup dispersion. We detected an inverse linear relationship between pre-training values and % of CPC changes post-training (p<0.001). In the CPC values 3 weeks after training this inverse relationship was maintained, though to a lower extent (p<0.001). No changes in CPC CD34(+) were detected after 6 weeks of different training groups, or after 3 weeks of follow-up.

We examined immunological responses in patients receiving histone deacetylase (HDAC) inhibition (vorinostat) for graft-versus-host disease prophylaxis after allogeneic hematopoietic cell transplant. Vorinostat treatment increased histone acetylation in peripheral blood mononuclear cells (PBMCs) from treated patients, confirming target HDAC inhibition. HDAC inhibition reduced proinflammatory cytokine levels in plasma and from PBMCs and decreased ex vivo responses of PBMCs to proinflammatory TLR-4 stimuli, but did not alter the number or response of conventional T cells to nonspecific stimuli. However, the numbers of regulatory T cells (Tregs) were increased, which revealed greater demethylation of the Foxp3 T regulatory-specific demethylation region. Vorinostat-treated patients showed increased expression of CD45RA and CD31 on Tregs, and these Tregs demonstrated greater suppression on a per cell basis. Consistent with preclinical findings, HDAC inhibition also increased signal transducer and activator of transcription 3 acetylation and induced indoleamine-2,3-dioxygenase. Our data demonstrate that HDAC inhibition reduces inflammatory responses of PBMC but enhances Tregs after allo-HCT.

This study aimed to investigate the safety and feasibility of intracoronary injection of human umbilical cord mesenchymal stem cell to the very old patients with coronary chronic total occlusion. 15 consecutive patients received mesenchymal stem cells from human umbilical cord in epicardial coronary artery supplying collateral circulation. The patients were randomly allocated to low-dose 3x10(6), mid-dose 4x10(6) and high-dose 5x10(6) groups. (99m)Tc single photon emission computed tomography images were obtained at 12 and 24 months. During the 24 month study period, no cases of major cardiac adverse events were reported. None of the patients had coronary care unit admissions hospitalizations further coronary revascularization acute myocardial infarction and death. The patients had a significant reduction of the infarct size and a remarkable rise in left ventricular ejection fraction with respect to secondary outcomes. This study suggested that stem cell transplantation was safe and feasible. The cells can be utilized to improve in the degree of ischemic myocardium, decrease in the infarct size and rise in left ventricular ejection fraction.

The graft of stem cells to treat ischemic cardiomyopathy is popular in many clinical trials. The aim of this study was to evaluate the effectiveness of isolated coronary artery bypass graft combined with bone marrow mononuclear cells (BMMNC) delivered through graft vessels to improve left ventricular function of patients with previous myocardial infarction and chronic heart failure using echocardiography.

Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear.