Bone Marrow-Derived Mesenchymal Stem Cells Improve the Functioning of Neurotrophic Factors in a Mouse Model of Diabetic Neuropathy

Diabetic neuropathy is one of the most frequent and troublesome complications of diabetes. Although there has been a continuous increase in the incidence of diabetic neuropathy, treatments have yet to be found that effectively treat diabetic neuropathy. Neurotrophic factors are proteins that promote the survival of specific neuronal populations. They also play key roles in the regeneration of peripheral nervous system. Recent evidence from diabetic animal models and human diabetic subjects suggest that reduced availability of neurotrophic factors may contribute to the pathogenesis of diabetic neuropathy. One way to reverse this effect is to take advantage of the finding that bone marrow derived mesenchymal stem cells (BM-MSCs) promote peripheral nerve repair and the functioning of neurotrophic factors. Therefore, we speculated that treatment with BM-MSCs could be a viable therapeutic strategy for diabetic neuropathy. The present study was designed to examine the possible beneficial effect of BM-MSCs on functions of neurotrophic factors in diabetic neuropathy. To assess this possibility, we used an in vivo streptozotocin-induced diabetic neuropathy mouse model. Quantitative real-time polymerase-chain reacion showed that BM-MSCs significantly increase expression levels of neurotrophic factors. Also, BM-MSCs ameliorated nerve conduction velocity in streptozotocin-treated mice. These results may help to elucidate the mechanism by which BM-MSCs function as a cell therapy agent in diabetic neuropathy

mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.

Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway

Advances in tissue engineering through stem cell-based co-culture

Stem cells are the future in tissue engineering and regeneration. In a co-culture, stem cells not only provide a target cell source with multipotent differentiation capacity, but can also act as assisting cells that promote tissue homeostasis, metabolism, growth and repair. Their incorporation into co-culture systems seems to be important in the creation of complex tissues or organs. In this review, critical aspects of stem cell use in co-culture systems are discussed. Direct and indirect co-culture methodologies used in tissue engineering are described, along with various characteristics of cellular interactions in these systems. Direct cell–cell contact, cell–extracellular matrix interaction and signalling via soluble factors are presented. The advantages of stem cell co-culture strategies and their applications in tissue engineering and regenerative medicine are portrayed through specific examples for several tissues, including orthopaedic soft tissues, bone, heart, vasculature, lung, kidney, liver and nerve. A concise review of the progress and the lessons learned are provided, with a focus on recent developments and their implications. It is hoped that knowledge developed from one tissue can be translated to other tissues. Finally, we address challenges in tissue engineering and regenerative medicine that can potentially be overcome via employing strategies for stem cel

New approaches to interfacing thermoelectric generators to the load bus in a nuclear space vehicle

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.Not availabl

Odlade mesenkymala stamcellers användning vid skador på perifera och centrala nervsystemet

Bone marrow-derived mesenchymal stem cells (MSC) have been shown to provide neuroprotection after transplantation into the injured nervous system. The present thesis investigates whether adult human and rat MSC differentiated along a Schwann cell lineage could increase their expression of neurotrophic factors and promote regeneration after transplantation into the injured peripheral nerve and spinal cord. Human and rat mesenchymal stem cells (hMSC and rMSC) expressed characteristic stem cell surface markers, mRNA transcripts for different neurotrophic factors and demonstrated multi-lineage differentiation potential. Following treatment with a cocktail of growth factors, the hMSC and rMSC expressed typical Schwann cells markers at both the transcriptional and translational level and significantly increased production of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Age and time in culture are of relevance for clinical settings and growth-promoting effects of hMSC from young donors (16-18 years) and old donors (67-75 years) were compared. Undifferentiated hMSC from both young and old donors increased total neurite length of cultured dorsal root ganglion (DRG) neurons. Differentiation of hMSC from the young donors, but not the eldery donors, further enhanced the neurite outgrowth. Undifferentiated hMSC were cultured for eleven weeks in order to examine the effect of in vitro expansion time on neurite outgrowth. hMSC from the young donors maintained their proliferation rate and their ability to enhance neurite outgrowth from DRG neurons. Using a sciatic nerve injury model, a 10mm gap was bridged with either an empty tubular fibrin glue conduit, or conduits containing hMSC, with and without cyclosporine treatment. Cells were labeled with PKH26 prior to transplantation. At 3 weeks after injury the conduits with cells and immunosuppression increased regeneration compared with an empty conduit. PKH26 labeled human cells survived in the rat model and the inflammatory reaction could be suppressed by cyclosporine. After cervical C4 hemisection, BrdU/GFP-labeled rMSC were injected into the lateral funiculus rostral and caudal to the spinal cord lesion site. Spinal cords were analyzed 2-8 weeks after transplantation. Transplanted MSC remained at the injection sites and in the trauma zone for several weeks and were often associated with numerous neurofilament-positive axons. Transplanted rMSC induced up-regulation of vascular endothelial growth factor in spinal cord tissue rostral to the injury site, but did not affect expression of brain-derived neurotrophic factor. Although rMSC provided neuroprotection for rubrospinal neurons and significantly attenuated astroglial and microglial reaction, cell transplantation caused aberrant sprouting of calcitonin gene-related peptide immunostained sensory axons in the dorsal horn. In summary these results demonstrate that both rat and human MSC can be differentiated towards the glial cell lineage, and show functional characteristics similar to Schwann cells. hMSC from the young donors represent a more favorable source for neurotransplantation since they maintain proliferation rate and preserve their growth-promoting effects in long-term cultures. The data also suggest that differentiated MSC increase expression of neurotrophic factors and support regeneration after peripheral nerve and spinal cord injury

Lön och lönsamhet : En kvantitativ studie om den verkställande direktörens ersättning och bolagets prestation

En verkställande direktör är direkt ansvarig över den löpande verksamheten i ett företag. Genom strategiska beslut kan VD:n påverka bolagets prestationer, denna typ av beslut har synnerligen stor inverkan på bolag verksamma inom högteknologiska branscher. Ett omtalat incitament som används i syfte att säkerställa att VD:n fattar beslut som är i linje med ägarnas vision är den ekonomiska ersättningen. Ersättningen som en VD erhåller har diskuterats flitigt i både media och vetenskapliga artiklar, detta då skeptiker menar på att ersättningen är omotiverat hög. Syftet med denna studie är att studera om det finns något samband mellan VD:ns ekonomiska ersättning och företagens prestation. Denna studie baseras på kvantitativ data avseende perioden 2015 till 2018 och testar genom statistiska test om det finns något signifikant samband mellan VD:ns ersättning och bolagets prestation. Utifrån tidigare forskning och det teoretiska ramverket som redovisas har fyra hypoteser tagits fram. Vidare har hypoteserna testats mot en femprocentig signifikansnivå. Utifrån resultatet kunde ingen av hypoteserna förkastas då inget signifikant samband gick att urskilja. Resultatet av denna studie stöds även av stewardshipteorin som hävdar att ekonomisk ersättning inte verkar som det enskilt starkaste incitamentet då VD:n snarare drivs av inre motiv. Denna studie ligger även i linje med resultatet av tidigare forskning.The chief executive officer is directly responsible for the day-to-day operations of a company. Through strategic decisions, the CEO can affect the company performance, this type of decision has a particularly great impact on companies operating in high-tech industries. A well-known incentive that is used to ensure that the CEO makes decisions that are in line with the owners' vision is the financial compensation. The remuneration received by a CEO has been widely discussed in both media and scientific articles, as skeptics believe that the compensation is unjustifiably high. The purpose of this study is to examine whether there is any correlation between the CEO's financial compensation and the companies' performance. This study is based on quantitative data for the period 2015 to 2018 and tests through statistical tests if there is any significant correlation between the CEO's remuneration and the company's performance. Based on previous research and the theoretical framework presented, four hypotheses have been developed. Furthermore, the hypotheses have been tested against a five percent significance level. Based on the result, none of the hypotheses could be rejected since no statistical significance could be proven. The result of this study is also supported by stewardship theory which claims that financial compensation does not act as the single strongest incentive, instead the theory claim that the CEO is driven by inner motives. This study is also in line with the results of previous research

Lön och lönsamhet : En kvantitativ studie om den verkställande direktörens ersättning och bolagets prestation

En verkställande direktör är direkt ansvarig över den löpande verksamheten i ett företag. Genom strategiska beslut kan VD:n påverka bolagets prestationer, denna typ av beslut har synnerligen stor inverkan på bolag verksamma inom högteknologiska branscher. Ett omtalat incitament som används i syfte att säkerställa att VD:n fattar beslut som är i linje med ägarnas vision är den ekonomiska ersättningen. Ersättningen som en VD erhåller har diskuterats flitigt i både media och vetenskapliga artiklar, detta då skeptiker menar på att ersättningen är omotiverat hög. Syftet med denna studie är att studera om det finns något samband mellan VD:ns ekonomiska ersättning och företagens prestation. Denna studie baseras på kvantitativ data avseende perioden 2015 till 2018 och testar genom statistiska test om det finns något signifikant samband mellan VD:ns ersättning och bolagets prestation. Utifrån tidigare forskning och det teoretiska ramverket som redovisas har fyra hypoteser tagits fram. Vidare har hypoteserna testats mot en femprocentig signifikansnivå. Utifrån resultatet kunde ingen av hypoteserna förkastas då inget signifikant samband gick att urskilja. Resultatet av denna studie stöds även av stewardshipteorin som hävdar att ekonomisk ersättning inte verkar som det enskilt starkaste incitamentet då VD:n snarare drivs av inre motiv. Denna studie ligger även i linje med resultatet av tidigare forskning.The chief executive officer is directly responsible for the day-to-day operations of a company. Through strategic decisions, the CEO can affect the company performance, this type of decision has a particularly great impact on companies operating in high-tech industries. A well-known incentive that is used to ensure that the CEO makes decisions that are in line with the owners' vision is the financial compensation. The remuneration received by a CEO has been widely discussed in both media and scientific articles, as skeptics believe that the compensation is unjustifiably high. The purpose of this study is to examine whether there is any correlation between the CEO's financial compensation and the companies' performance. This study is based on quantitative data for the period 2015 to 2018 and tests through statistical tests if there is any significant correlation between the CEO's remuneration and the company's performance. Based on previous research and the theoretical framework presented, four hypotheses have been developed. Furthermore, the hypotheses have been tested against a five percent significance level. Based on the result, none of the hypotheses could be rejected since no statistical significance could be proven. The result of this study is also supported by stewardship theory which claims that financial compensation does not act as the single strongest incentive, instead the theory claim that the CEO is driven by inner motives. This study is also in line with the results of previous research

Räntesnurror : Hur fungerar de, och vilka argument finns för och emot dem?

Titel: Räntesnurror - hur fungerar de, och vilka argument finns för och emot dem?   Nivå: C-uppsats i ämnet företagsekonomi   Författare: Jessica Bjurman, Katarina Brohlin   Handledare: Markku Penttinen   Datum: 2013 - 02 - 20   Syfte: Syftet med denna uppsats är att inom ramen för det företagsekonomiska ämnet forska    kring begreppet räntesnurror. Räntesnurror innebär skatteplanering med ränteavdrag som sänker bolagsskatten och därmed skänker verksamheten en ekonomisk fördel. Forskningen fokuserar på att vidare ta reda på vad räntesnurror är, och vilka argument som finns för och emot dem. Även den nya lagstiftningen kommer att studeras, för att undersöka vilka konsekvenser den kan komma att medföra för svenska företag.   Metod: Denna studie grundar sig på en kvalitativ metod, med utgångspunkt i det hermeneutiska synsättet. Primärdata har ansamlats genom ett flertal intervjuer med bl.a. företag, institutioner och myndigheter, sekundärdata har hämtats från lagförslag, lagrådsremisser, praxis, litteratur m.m. Med hjälp av välkända, vetenskapliga teorier har informationen sedan tolkats och analyserats, och slutligen mynnat i uppsatsens slutsats.   Resultat och slutsats: De företag som kommer att påverkas av den nya lagen är de företag som ingår i en intressegemenskap, vars ränteavdrag inte kan bevisas är affärsmässigt motiverade och som inte undantas p.g.a. den s.k. tioprocentsregeln. Dessa företag kommer att förlora värdet av den skattesköld som räntesnurrorna skapat, varpå företagens finansiering kan påverkas i riktning mot en ökad extern belåning. Detta då ränteavdrag inte längre får göras för interna skuldförhållanden och det vinsttillskott som detta tidigare skapat nu kommer att försvinna, för att kunna behålla sin verksamhetsnivå kan företagen då tvingas ta externa lån vilket leder till ökade obeståndskostnader och lägre företagsvärden. Även investeringsklimatet påverkas negativt, då kalkylerna blir osäkra till följd av den oförutsägbarhet den nya lagen skapar, vilket kan leda till försämrad tillväxt för svenska företag. Från januari 2013 ändrades bolagsskatten från 26,3 till 22 %. Detta bör kunna innebära att bolag som tidigare skatteplanerat på ett icke affärsmässigt sätt nu inte har samma behov av att skatteplanera i samma utsträckning. Svenskt Näringsliv tror även att bortfallet i och med detta kommer att kompenseras av lagstiftandet mot ränteavdragen. För de företag som inte tidigare använt sig av ett skatteplanerande med ränteavdrag innebär den sänka bolagsskatten ett positivt inslag i verksamheten.   Förslag till fortsatt forskning: Den nya lagens faktiska genomslag och vilka effekter den får är i dagsläget svårt att bedöma. Att genomföra en studie om 3-5 år som lägger fokus på statistiska fakta för att utreda de effekter lagförändringen medfört vore därför mycket intressant.   Uppsatsens bidrag: Att påvisa vilka effekter externa faktorer, såsom förändrad skattelagstiftning, kan ha på företagens ekonomiska situation.   Nyckelord: Räntesnurror, kapitalstruktur, finansiering, interna skuldförhållanden, trade-off teorin, pecking-orderhypotesen

Evaluation of growth, stemness, and angiogenic properties of dental pulp stem cells cultured in cGMP xeno-/serum-free medium

This study was aimed to investigate the effects of cGMP xeno-/serum-free medium (XSF, Irvine Scientific) on the properties of human dental pulp stem cells (DPSCs). DPSCs, from passage 2, were cultured in XSF or fetal bovine serum (FBS)-supplemented medium, and sub-cultured up to passage 8. Cumulative population doublings (PDs) and the number of colony-forming-units (CFUs) were determined. qRT-PCR, ELISA, and in vitro assays were used to assess angiogenic capacity. Flow cytometry was used to measure CD73, CD90, and CD105 expression. Differentiation into osteo-, adipo-, and chondrogenic cell lineages was performed. DPSCs showed more elongated morphology, a reduced rate of proliferation at later passages, and lower CFU counts in XSF compared with FBS. Expression of angiogenic factors at the gene and protein levels varied in the two media and with passage number, but cells grown in XSF had more in vitro angiogenic activity. The majority of early and late passage DPSCs cultured in XSF expressed CD73 and CD90. In contrast, the percentage of CD105 positive DPSCs in XSF medium was significantly lower with increased passage whereas the majority of cells cultured in FBS were CD105 positive. Switching XSF-cultured DPSCs to medium supplemented with human serum restored the expression of CD105. The tri-lineage differentiation of DPSCs cultured under XSF and FBS conditions was similar. We showed that despite reduced CD105 expression levels, DPSCs expanded in XSF medium maintained a functional MSC phenotype. Furthermore, restoration of CD105 expression is likely to occur upon in vivo transplantation, when cells are exposed to human serum