PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “MSC”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

Mosaic (MSC) cucumbers regenerated from independent cell cultures possess different mitochondrial rearrangements.

Passage of the highly inbred cucumber ( Cucumis sativus L.) line B through cell culture produces progenies with paternally transmitted, mosaic (MSC) phenotypes. Because the mitochondrial genome of cucumber shows paternal transmission, we evaluated for structural polymorphisms by hybridizing cosmids spanning the entire mitochondrial genome of Arabidopsis thaliana L. to DNA-gel blots of four independently generated MSC and four wild-type cucumbers. Polymorphisms were identified by cosmids carrying rrn18, nad5-exon2, rpl5, and the previously described JLV5 deletion. Polymorphisms revealed by rrn18 and nad5-exon2 were due to one rearrangement bringing together these two coding regions. The polymorphism revealed by rpl5 was unique to MSC16 and was due to rearrangement(s) placing the rpl5 region next to the forward junction of the JLV5 deletion. The rearrangement near rpl5 existed as a sublimon in wild-type inbred B, but was not detected in the cultivar Calypso. Although RNA-gel blots revealed reduced transcription of rpl5 in MSC16 relative to wild-type cucumber, Western analyses revealed no differences for the RPL5 protein and the genetic basis of the MSC16 phenotype remains enigmatic. We evaluated 17 MSC and wild-type lines regenerated from independent cell-culture experiments for these structural polymorphisms and identified eight different patterns, indicating that the passage of cucumber through cell culture may be a unique mechanism to induce or select for novel rearrangements affecting mitochondrial gene expression.

Cells, Cultured↗

Methyltransferase METTL1 regulates MSC mRNA stability via m7G modification in acute pancreatitis.

Acute pancreatitis (AP) is a serious inflammatory disease with significant morbidity, yet its underlying molecular mechanisms remain incompletely understood. This study reveals a novel epitranscriptomic pathway in AP pathogenesis centered on METTL1-mediated N7-methylguanosine (m7G) RNA modification. We found that METTL1 expression and global m7G levels were significantly elevated in serum from AP patients, pancreatic tissues of sodium taurocholate-induced AP mice, and in vitro models of LPS-polarized macrophages and STC-injured pancreatic acinar cells. Through integrated multi-omics analysis combining m7G methylome mapping and transcriptome profiling, we identified Musculin (MSC) as a key target whose mRNA stability is enhanced by METTL1-mediated m7G modification. Functional experiments demonstrated that MSC upregulation activates TNF signaling through phosphorylation of NF-κB, JNK, and MAPK proteins, thereby promoting macrophage M1 polarization and pancreatic acinar cell injury. The pathological significance of this pathway was confirmed in vivo, where pancreas-targeted knockdown of Mettl1 significantly attenuated AP severity. Furthermore, mechanistic studies using a catalytic-dead METTL1 mutant established that both the methyltransferase activity of METTL1 and subsequent TNF signaling activation are essential for driving inflammatory responses. Our findings delineate a previously unrecognized METTL1-m7G-MSC-TNF signaling axis that promotes AP progression, highlighting the therapeutic potential of targeting METTL1-mediated epitranscriptomic modification in inflammatory diseases.

Animals↗

Multilineage differentiation of human MSC after in utero transplantation.

Prenatal transplantation of stem cells is an exciting frontier for the treatment of many congenital diseases. The fetus may be an ideal recipient for stem cells, as it is immunologically immature and has rapidly proliferating cellular compartments that may support the engraftment of transplanted cells. Mesenchymal stem cells (MSC), given their ability to differentiate among multiple lineages, could potentially be used to treat diseases such as osteogenesis imperfecta, muscular dystrophy, and a variety of others that can be diagnosed in utero. We have shown, using a human-sheep in utero xenotransplantation model, that human MSC have the ability to engraft, differentiate into many tissue types, and survive for over 1 year in fetal lamb recipients. This observation warrants further studies of the behavior of MSC following systemic or site-directed transplantation.

Animals↗

Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement.

The plastic-adherent cells isolated from BM and other sources have come to be widely known as mesenchymal stem cells (MSC). However, the recognized biologic properties of the unfractionated population of cells do not seem to meet generally accepted criteria for stem cell activity, rendering the name scientifically inaccurate and potentially misleading to the lay public. Nonetheless, a bona fide MSC most certainly exists. To address this inconsistency between nomenclature and biologic properties, and to clarify the terminology, we suggest that the fibroblast-like plastic-adherent cells, regardless of the tissue from which they are isolated, be termed multipotent mesenchymal stromal cells, while the term mesenchymal stem cells is used only for cells that meet specified stem cell criteria. The widely recognized acronym, MSC, may be used for both cell populations, as is the current practice; thus, investigators must clearly define the more scientifically correct designation in their reports. The International Society for Cellular Therapy (ISCT) encourages the scientific community to adopt this uniform nomenclature in all written and oral communications.

Mesenchymal Stem Cells↗

Regulation of protein kinase A subunits by cyclic adenosine 3',5'-monophosphate in a mouse Sertoli cell line (MSC-1): induction of RII beta messenger ribonucleic acid is independent of continuous protein synthesis.

We report the basal and cAMP-regulated expression of protein kinase A (PKA) subunits in a mouse Sertoli cell line (MSC-1). Of the PKA subunits expressed by these cells (RI alpha, RII alpha, RII beta, C alpha, C beta), only RII beta was regulated by cAMP. An approximately 8-fold induction of RII beta mRNA and a 3-fold induction of RII beta protein was observed during 48 h of cAMP-stimulation. This cAMP-mediated RII beta mRNA induction, reaching maximal levels after approximately 12 h, did not require ongoing protein synthesis. Fairly rapid decay of maximally induced RII beta mRNA was observed after removal of cAMP (t1/2 approximately 5 h). Further, ongoing transcription and translation were necessary for rapid degradation of RII beta mRNA. Thus, the MSC-1 cells expressed all the PKA subunits present in primary cultures of Sertoli cells and responded to cAMP with increased levels of RII beta at both mRNA and protein levels. Although the nature of some of these responses distinguished the observations in MSC-1 cells from previously described responses in primary cultures, these cells may prove to be useful in future studies addressing cAMP-mediated gene regulation.

Animals↗

Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord.

Mesenchymal stem cells (MSCs) have the capability for renewal and differentiation into various lineages of mesenchymal tissues. These features of MSCs attract a lot of attention from investigators in the context of cell-based therapies of several human diseases. Despite the fact that bone marrow represents the main available source of MSCs, the use of bone marrow-derived cells is not always acceptable due to the high degree of viral infection and the significant drop in cell number and proliferative/differentiation capacity with age. Thus, the search for possible alternative MSC sources remains to be validated. Umbilical cord blood is a rich source of hematopoietic stem/progenitor cells and does not contain mesenchymal progenitors. However, MSCs circulate in the blood of preterm fetuses and may be successfully isolated and expanded. Where these cells home at the end of gestation is not clear. In this investigation, we have made an attempt to isolate MSCs from the subendothelial layer of umbilical cord vein using two standard methodological approaches: the routine isolation of human umbilical vein endothelial cell protocol and culture of isolated cells under conditions appropriate for bone-marrow-derived MSCs. Our results suggest that cord vasculature contains a high number of MSC-like elements forming colonies of fibroblastoid cells that may be successfully expanded in culture. These MSC-like cells contain no endothelium- or leukocyte-specific antigens but express alpha-smooth muscle actin and several mesenchymal cell markers. Therefore, umbilical cord/placenta stroma could be regarded as an alternative source of MSCs for experimental and clinical needs.

Endothelium, Vascular↗

The UMDS MSc in general practice: attainment of intended outcomes.

BACKGROUND: The United Medical and Dental School's (UMDS's) MSc in general practice is one of the longest running courses of its kind. Although descriptive accounts of such courses have been published, little is known about their outcomes. AIM: To measure the extent to which graduates feel they have personally achieved 16 intended outcomes derived from the course objectives, and to record current academic activities, particularly teaching and research. METHOD: A postal questionnaire to graduates of the UMDS MSc in General Practice. RESULTS: The response rate was 93%. Of the 71 responders, 23 have gone on to register for or complete other degrees or diplomas. Over two-thirds of responders had an academic commitment following the MSc. Two-thirds were currently engaged in research and over half reported having had work accepted for publication. The majority of graduates confirmed the attainment of all 16 outcomes, although outcomes related to personal achievements were endorsed more strongly than those related to service delivery. CONCLUSION: UMDS graduates are making a significant contribution to their discipline and are unanimous in describing the course as an important event in their personal development. As a result of this study, the course organizers are seeking to increase the links between academic study and everyday practice.

Adult↗

111-indium human antimyosin monoclonal antibody-fragment study on alcoholic (and diabetic) cardiomyopathic patients (ACM-DCM) with Centocor Europe Myoscint (Msc).

The criteria of Msc-positivity were: typical accumulation of hot spots in 2 directions of planar scan in the 24-48-hr measurements, while in atypical cases the hot spots were present only in the 48 hr picture. Twenty-one male volunteers were assessed. 18 of them had ACM (2 patients were studied repeatedly). The negative and positive control cases exhibited the expected Msc pattern. Seven ACM patients were regarded typically positive, in 5 cases atypical positivity was stated, and 6 patients were classified as Msc negatives. The heart lung activity ratio was 1.75 +/- 0.45 and 1.68 +/- 0.44 for typical and atypical positive cases, respectively. The control and DCM H/L ratios were 1.15 and 1.3 +/- 0.2, respectively, in AMI the H/L was 1.91, in DCM of dilatative phase it was 1.55 +/- 0.06 with serum myosin in the normal range. Heart dilation in the DCM groups: 5 dilated out of 7 typically positive cases while in atypically positive, and negative cases the dilation occurred in 2 out of 5 and 1 out of 6 cases, respectively. Low LV-EF (less than 45%) were found in ratios of 4/7, 2/5, and 1/6 in typically positive, atypically positive and negative cases, respectively. Elevated PCP similar ratios. In the same groups pathological ECG was seen in ratios of 5/7, 1/5, and 1/6, respectively. The g-GT activity was enhanced in all cases, there was, however, no evident correlation between the actual enzyme activity and intensity of hot accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Simultaneous determination of beta-lactamic antibiotics by a new high-performance low-pressure chromatographic system using a multisyringe burette coupled to a monolithic column (MSC).

A technique based on multisyringe chromatography (MSC) was developed to determine three beta-lactamic antibiotics. Amoxicillin (AMOXI), ampicillin (AMPI) and cephalexin (CEPHA) were analyzed using a system with a very simple design and very low-cost equipment consisting of a multisyringe module, three low-pressure solenoid valves, a monolithic Chromolith Flash RP-18e column and a diode array spectrophotometric detector monitoring at 250 nm. Mobile phases containing methanol:acetic acid (0.1 M)-sodium acetate (0.1 M), pH 6.2, were tested for various ratios of methanol:acetic acid-sodium acetate, but a ratio of 10:90 gave optimum results with a flow rate of 2 ml min(-1). Validation parameters were evaluated for amoxicillin. The response to amoxicillin was linear over the range 0.04-0.4 mg/mL, with a correlation coefficient of 0.9996; precisions, evaluated as the repeatability for 0.04, 0.16 and 0.4 mg/mL amoxicillin, were 0.6%, 0.1% and 0.6%, respectively. Recovery from a generic formulation of amoxicillin was evaluated. The method showed selectivity in the presence of excipients commonly used in capsules, and satisfactory specificity was observed for amoxicillin and hydrolytic degradation products. The linearity was also evaluated for cephalexin and ampicillin. The conditions selected for MSC separation were compared with those for a HPLC system, and similar results were obtained in terms of chromatographic parameters but a difference in retention times was observed.

Amoxicillin↗

Inhibition of human immunodeficiency virus type 1 wild-type and mutant reverse transcriptases by the phenyl ethyl thiazolyl thiourea derivatives trovirdine and MSC-127.

A new class of very potent and selective non-nucleoside inhibitors of HIV reverse transcriptase (RT) has recently been identified. The prototype compound trovirdine (LY 300046 HCl) and one analogue, MSC-127, have been studied with respect to inhibition of wild-type HIV-1 RT and RT with various mutations known to give rise to resistance to other non-nucleoside RT inhibitors, namely Leu100-->Ile (Ile100), Glu138-->Arg (Arg138), Tyr181-->Cys (Cys181) and Tyr188-->His (His188). The inhibition of HIV-1 RT by trovirdine and MSC-127 was reversible and template dependent. Trovirdine inhibited HIV-1 RT with an IC50 of 0.007 microM when employing heteropolymeric primer/template (oligo-DNA/ribosomal RNA) and dGTP as substrate. Enzyme kinetic studies showed that inhibition of RT by trovirdine was non-competitive with regard to deoxynucleoside triphosphates and uncompetitive with respect to varied primer/template under steady-state conditions. The amino acid changes Leu100, Tyr181 and Tyr188 gave rise to 25-, 147- and 12-fold decrease in inhibition by trovirdine. Enzyme-kinetic studies on trovirdine have been carried out using various RT mutants and compared to the properties of the earlier reported non-nucleoside RT inhibitors 9-Cl-TIBO, nevirapine and L-697,661.

Antiviral Agents↗

Mesenchymal stem/stromal cells (MSC) transfected with stromal derived factor 1 (SDF-1) for therapeutic neovascularization: enhancement of cell recruitment and entrapment.

Recruited bone marrow-derived circulating cells (RBCCs) play a key role in therapeutic neovascularization. Several important steps take place during this process, which include mobilization, migration, recruitment, adhesion and invasion, entrapment, differentiation, as well as paracrine functions. Recent study indicated that recruitment and entrapment of RBCCs are vital steps in vascular endothelial growth factor (VEGF)-induced angiogenesis. This entrapment is modulated by another important chemokine: stromal derived factor 1 (SDF-1). We reason that the enhancement of entrapment might be a novel target for therapeutic neovascularization. Therefore we hypothesize that mesenchymal stem/stromal cells that secrete VEGF in situ could be transfected with SDF-1 (MSC(SDF-1)). Their combination could augment mobilization, recruitment, survival, and above all the entrapment of RBCCs, all of which might greatly augment the angiogenesis pathway. For these reasons, we further hypothesize that MSC(SDF-1) might become a next generation cell/chemokine therapy for therapeutic neovascularization.

Chemokine CXCL12↗

The United Medical and Dental School of Guy's and St Thomas' Hospitals' MSc in general practice: graduates' perspectives.

AIM: Higher degrees have been proposed as one means whereby general practitioners can continue their professional development and avoid a slow decline into professional isolation and burnout. The United Medical and Dental School of Guy's and St Thomas' Hospitals' MSc in general practice has been available to experienced general practitioners for over a decade. This study reports some of the outcomes of participation for the 76 graduates of the first nine cohorts. METHOD: As part of an ongoing programme of evaluation the graduates were sent a questionnaire which, in addition to seeking information about attainment of intended outcomes, gave respondents the opportunity to write freely about the contribution made by the course to their own professional and personal development. Seventy-one graduates completed the questionnaire, a response rate of 93%. RESULTS AND CONCLUSIONS: An increased confidence that arises not only from a broadened knowledge base and increased skills but also from a sense of having been enabled to explore more deeply into their discipline, is the most frequently and highly valued outcome of participation. Graduates appreciated having additional protected time and demonstrated an ability to use it productively. A further significant outcome was the ability of the course to confront those habitual assumptions of doctors which inform their practice in a manner that was both challenging and supportive. Tendencies to professional isolation and burnout appear to have been reversed with a greater sense of connectedness to their discipline. Doctors seeking to diversify their general practice careers beyond the task of providing medical services have found the MSc an important route for change.

Attitude of Health Personnel↗

Neural transplantation of human MSC and NT2 cells in the twitcher mouse model.

BACKGROUND: Accumulating evidence has demonstrated that the NT2 embryonal carcinoma cell line and multipotential stem cells found in BM, mesenchymal stromal cells (MSC), have the ability to differentiate into a wide variety of cell types. This study was designed to explore the efficacy of these two human stem cell types as a graft source for the treatment of demyelinating disorders such as Krabbe's disease and multiple sclerosis (MS). METHODS: We examined the engraftment and in vivo differentiation of adult MSC and NT2 cells after transplantation into two demyelinating environments, the neonatal and postnatal twitcher mouse brain. RESULTS: Both types of xenografts led to anatomical integration, without tumor formation, and remained viable in the normal and twitcher mouse brain, showing differentiation into neurons, astrocytes and oligodendrocytes. DISCUSSION: This study represents a platform for further stem cell transplantation studies in the twitcher model and potentially has important therapeutic implications.

Animals↗

Adult bone marrow stem/progenitor cells (MSCs) are preconditioned by microenvironmental "niches" in culture: a two-stage hypothesis for regulation of MSC fate.

Mesenchymal stem cells (MSCs) are clonal, plastic adherent cells from bone marrow that can differentiate into various tissue lineages, including osteoblasts, adipocytes, chondrocytes, myoblasts, hepatocytes, and possibly even neural cells. Because MSCs are multipotent and their numbers are easily expanded in culture, there has been much interest in their clinical potential for tissue repair and gene therapy. Consequently, numerous studies have been carried out demonstrating the migration and multiorgan engraftment potential of MSCs in animal models and in human clinical trials. Understanding the mechanisms behind MSC cell fate determination is not easy, because the molecular processes that drive engraftment and differentiation are complex. Even in an in vitro system, the molecular cues necessary to induce differentiation are not easily identified or reproduced. In this Perspective, we emphasize the importance of microenvironmental factors in culture and suggest that MSC differentiation in vitro is regulated by a two-stage mechanism involving preconditioning by factors in the culture microenvironment followed by response to soluble differentiating factors.

Adult↗

Developing learning outcomes for an ideal MSc course in sports and exercise medicine.

OBJECTIVE: To develop learning outcomes for an ideal MSc in sports and exercise medicine. METHODS: Twenty nine learning outcomes were developed based on the learning outcomes, aims, and objectives of current sports medicine courses, occupational standards, and other related data. Using a Likert scale, the opinion of MSc/Dip course directors in the United Kingdom, Ireland, Australia, New Zealand, and South Africa as well as teachers, graduates, and students of the MSc/Dip course at the University of Nottingham were surveyed. An email questionnaire listing the 29 learning outcomes was sent to the subjects. A mixed reminder via email or mail was used. The results were treated as ordinal data, and reliability and internal consistency of the questionnaire was tested using Cronbach's coefficient alpha. RESULTS: Response rates were high (75% course directors, 79%, 54%, and 78% University of Nottingham teachers, graduates, and students respectively). The questionnaire was highly reliable (alpha>0.8). The total scores of all but one of the responders were above the midpoint (>87, possible range 29-145). Most course directors (>80%) agreed or strongly agreed with each of the learning outcomes, except two. Most of the other subjects also agreed or strongly agreed with the learning outcomes, with few exceptions. CONCLUSION: The results suggest that there is a consensus among subjects that the final listed learning outcomes should be included in an ideal MSc in sports and exercise medicine.

Attitude of Health Personnel↗

Effectiveness of the MSC cold cap system in the prevention of chemotherapy-induced alopecia.

OBJECTIVE: To study the effectiveness of the MSC cold cap system to prevent chemotherapy-induced alopecia. METHODS: The system was applied in 83 cancer patients (mean age 49.8 years) undergoing chemotherapy with alopecia-causing agents. Seven patients did not tolerate the system. Seventy-six patients were evaluable for assessment; 26 received anthracycline (group A), 33 taxane (group T), 5 anthracycline plus taxane (group AT), 7 intravenous etoposide (group E) and 5 ifosfamide with or without other alopecia-causing drugs (group I). In group A, 18 patients received conventional (subgroup Ac) and 8 high doses (subgroup Ah). In group T, 8 patients received docetaxel (subgroup D) and 25 paclitaxel (subgroup P). Alopecia grade 0-1 (Dean's system) was considered as treatment success. RESULTS: Grade 0-1 alopecia was achieved in 49/76 (64.5%) patients: group T 23/33 (69.6%), subgroup P 16/25 (64%) and subgroup D 7/8 (87.5%); group A 18/26 (69.2%), subgroup Ac 16/18 (88.8%) and subgroup Ah 2/8 (25%); group AT 1/5 (20%); group E 6/7 (85.7%), and group I 1/5 (20%). CONCLUSIONS: The MSC cold cap system is effective in preventing alopecia from anthracycline, etoposide or taxane but not from anthracycline-taxane combinations or ifosfamide-containing regimens.

Adult↗

PIP3 antagonist as a molecular regulator in MSC-derived cardiomyocytes: Potential in vitro therapeutic implications for conotruncal heart defects.

Conotruncal heart defects (CTDs) account for approximately one-third of all congenital heart defects. Elevated levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) may contribute to CTD pathogenesis. PIP3 plays a pivotal role in mechanotransduction-based biological processes and remodeling of cardiac cytoskeletal proteins. Here, we aimed to evaluate the efficacy of the 322PESB derivative compound as a molecular regulator that antagonizes PIP3 binding pleckstrin homology (PH) domain of the Akt protein using mesenchymal stem cell-derived cardiomyocyte. Human adipose-derived MSCs (Ad-MSCs) were isolated. Immunophenotypic features of the hAd-MSCs were characterized according to minimal criteria of the international society for cellular therapy (ISCT) including immunophenotyping and trilineage differentiation potential. Subsequently, the differentiated hAd-MSCs were cultured in cardiomyogenesis-inducing medium. Successfully differentiated cardiomyocytes were assessed by measuring the expression levels of cardiomyocyte-specific genes using RT-qPCR. PIP3-primed cardiomyocytes were treated with 10 and 30 μmol/L of a 322PESB derivative molecule. The results showed a typical MSCs with high expression levels of CD73 (77.55%), CD90 (87.59%) and CD105 (91.88%) and that was accompanied by low expression levels of CD34 (0.59%) and CD45 (1.78%). After 21 days of MSC culture, cardiomyocyte-like cells with prominent striations were observed. Subsequent confirmation by RT-qPCR quantification of ADRB1 and MLC2a expression levels showed an average increase of 2.9-fold and 2.1-fold, respectively, in induced cardiomyocytes. Compared with the untreated control, PIP3 ELISA assay showed a significant increase in PIP3 levels in PIP3(10 nmol/L)-primed cardiomyocytes treated with 10 and 30 μmol/L of the 322PESB molecule derivative by 485.804 and 3564.164 ng/mL, respectively. In this study, we conducted the first promising molecular regulator with potential therapeutic implications for CTD patients. Further functional animal model and clinical phase studies are recommended.

Cardiomyocyte↗

A short internal eliminated sequence with central conserved sequences interrupting the LA-MSC gene of the 81 locus in the hypotrichous ciliates Oxytricha fallax and O. trifallax.

IES-LA is a short Internal Eliminated Sequence interrupting LA-MSC, a protein-coding gene of the 81 locus of Oxytricha fallax and O. trifallax. IES-LA is precisely excised from the gene during development of the macronucleus. The internal eliminated sequence is bounded by CAAT ... AATG, and thereby resembles a TBE1 transposon internal eliminated sequence insertion that is grossly shortened (4.1 kbp to 52-64 bp), consistent with the hypothesis that short IESs are degenerated ancient transposons. The pattern of sequence conservation between five alleles of IES-LA shows that it differs from previously characterized classes of ciliate short IESs: while many short IESs have conserved ends and diverged centers, IES-LA is more conserved in its center and its ends are diverged. This implies a excision mechanism for IES-LA that is distinct from those for other known Oxytricha IESs.

Animals↗