<i>Ex Vivo</i>Expansion of Hematopoietic Stem- and Progenitor Cells from Cord Blood in Coculture with Mesenchymal Stroma Cells from Amnion, Chorion, Wharton's Jelly, Amniotic Fluid, Cord Blood, and Bone Marrow

Klein, Caroline; Strobel, Julian; Zingsem, J.; Richter, R.H.; Goecke, Tamme W.; Beckmann, Matthias W.; Eckstein, Reinhold; Weisbach, Volker

doi:10.1089/ten.tea.2013.0073

Cited by 33 publications

(23 citation statements)

References 15 publications

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“…Hematopoietic stem and progenitor cell (HSPC) expansion was achieved by culturing hematopoietic cells on feeder cells derived from various sources including bone marrow[54–59], fetal liver[60–62], UCB[63] or central nervous system[64]. …”

Section: Ex Vivo Expansion Of Transduced Hscsmentioning

confidence: 99%

Optimizing autologous cell grafts to improve stem cell gene therapy

Psatha

Karponi

Yannaki

2016

Experimental Hematology

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Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically-engineered hematopoietic stem cells (HSCs) are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels post-transplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by a reduced intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing mega-doses of genetically-modified CD34+cells into conditioned patients or by transplanting HSCs with high engrafting and repopulating potential. In the present review, based on the lessons gained from the cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of HSCs for transplantation or/and their engraftability, as a platform towards the optimization of engineered stem cell grafts.

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Section: Ex Vivo Expansion Of Transduced Hscsmentioning

confidence: 99%

Optimizing autologous cell grafts to improve stem cell gene therapy

Psatha

Karponi

Yannaki

2016

Experimental Hematology

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“…The value of BM derived MSC have been shown by Robinson et al [41] in earlier work and MSC sources other than bone marrow (such as placental tissues) were suggested to reach better supporting conditions lately [42].…”

Section: Co-culturing With Mesenchymal Stem Cells (Msc)/stromal Cellsmentioning

confidence: 88%

Modalities to Improve Cord Blood Engraftment

Yurdakul¹

2014

J Stem Cell Res Ther

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Umblical cord blood (UCB) is one of the major sources of Hematopoietic Stem Cell Transplantation (HSCT) with increasing use in clinical practice. UCB can be a life saver for patients who do not have a matched unrelated adult donor or for patients who are in need of an urgent transplantation. Various factors make UCB a significant source of Hematopoietic Stem Cells (HSCs), including ease of procurement and lack of donor attrition, with the ability to process and long term storage of donor cells. Importantly, UCB donations can be used right away without the need for a "perfect" HLA match, thereby increasing donor access to HSCT, particularly for minority and mixed ethnicity patients, for whom a suitably matched related or unrelated donor may be difficult to locate. The major limitation of UCB is the quantity of cells to be infused. Although high proliferative potential allows one log less use of HSCs (HSC<10 5 /kg) compared to bone marrow (BM) or peripheral blood mononuclear cells (PBSC), even this amount cannot be reached in the majority of patients under donor search. When total nucleated cell (TNC) and CD34+ cell doses in UCB grafts are analyzed, a high correlation is observed with the rate of neutrophil and platelet engraftment, the incidence of graft failure and early transplant-related complications. It has been shown that UCB grafts with more than 3/6 HLA mismatches and with cell doses under the defined minimum threshold lead to higher transplantation related mortality (TRM). Especially when adult cord blood transplantation (UCBT) is the subject, providing units with enough cells remains the major drawback.Despite certain efforts, there is still an unmet need for increasing HSC cell dose and/or stimulating engraftment without loss of their long term repopulating (LTR) potential and reducing graft versus host disease (GVHD). Intrinsic and extrinsic cellular factors have been proven to act roles in HSC expansion thus justifying their role in in vitro and ex vivo culture conditions. Attempts to regulate these factors through ex vivo expansion methods aim to overcome insufficient cell numbers while methods promoting HSC homing is in favor of the latter. Combination of both appear to work synergistically. Induction or adoptive transfer of UCB derived immune cells particularly Natural Killer (NK) cells and regulatory T cells (T reg) with or without cytokines are also effective approaches for gaining better engraftment levels after UCBT. All of these approaches have been denoted as "successful" in pre-clinical in vitro and animal studies. Many of them have also been tested in early/later phase clinical trials resulting in encouraging results. We aim to review the current knowledge on UCB expansion and engraftment enhancer methods, a very rapidly improving field particularly in the last decade.Eltrombopag enhanced expansion of HSC/HPC of human UCB in vivo and in vitro, and promoted multi-lineage hematopoiesis through the expansion of BM HSC/HPC of human UCB in vivo. A novel c-MPL agonist, a small molecule, ...

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“…It is well known that infection may cause an increase in maternal serum and amniotic fluid G-CSF values. In a literature search, the existence of G-CSF was described during clinically diagnosed intra-amniotic infection in amniotic fluid (14)(15)(16)(17), and its relationship to labor was reported as either increased serum levels of G-CSF or no difference between term-and preterm-delivered patients (4,5). In our study, any participant with any sign of infection was excluded in order to eliminate a bias in G-CSF levels.…”

Section: Discussionmentioning

confidence: 99%

Comparison of serum granulocyte colony-stimulating factor levels between preterm and term births

Kılıç

Uğur

Ünlü

et al. 2014

J Turkish German Gynecol Assoc

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Material and MethodsThis study was conducted between January 2011 and July 2011 in our perinatology clinic. Ethics approval was obtained from our institutional review board. Informed consent was given by all study participants. The study was designed as a prospective case-control study. PTB was defined as a delivery that occurs before the 37th week of gestation (9,10). Inclusion criteria in the study group were singleton pregnancies with a diagnosis of preterm labor leading to preterm birth at or before 37 weeks of gestation. Women who had preterm premature membrane rupture (P-PROM), clinical signs of intrauterine infection (uterine tenderness, fetal or maternal tachycardia, maternal fever, etc.), or bacterial infection in the cervical/vaginal culture were not included in the study or control groups. Also, women who had a history of maternal cardiac disease, cervical incompetence, cervical cerclage or conization, fetal anomaly, or vaginal bleeding were excluded from the study and control groups. A total of 600 singleton pregnant women were screened at 24-28 weeks of gestation and routinely followed up at the outpatient clinic until delivery. Demographic values of all pregnant women were recorded. Forty pregnant women delivered their infants spontaneously after preterm labor before 37 weeks of gestation. Also, 120 pregnant women were selected as a control group among these 560 women via a simple random sampling method, who delivered their infants after 37 weeks of gestation. All participants had 24-28-week plasma samples available for granulocyte colony-stimulating factor analysis. For both groups, maternal blood samples were collected at 24-28 weeks of gestation during a routine prenatal screening program in the outpatient clinic. Venous blood samples from patients were collected into sterile, silicone-coated tubes, centrifuged, and stored at -70°C. Maternal serum G-CSF levels were measured with the G-CSF Human Enzyme-Linked Immunosorbent Assay (ELISA) kit (Novex®; Invitrogen, Los Angeles, USA). The Statistical Package for the Social Sciences 14.0 (SPSS Inc.; Chicago, IL, USA) statistical package was used for the statistical analysis. Descriptive statistical methods (mean, standard deviation), as well as a comparison of quantitative data, MannWhitney U-test, chi-square test, and Student's t-test, were used for the determination of differences between the two groups. Statistically significant levels for the tests were set at a p value <0.05. Spearman's rank correlation coefficient rho was used for the correlation study. ResultsThe characteristics of 160 women and the comparison of the two groups are shown in Table 1. The difference of the mean age of the women between groups was not statistically significant (p=0.8). There were no significant differences in maternal serum G-CSF levels between groups (p=0.28). Smoking status was different between cases of PTB and fullterm pregnancies, but a statistically significant difference was not found (p=0.284). ROC curve analysis was performed for the prediction of...

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Ex VivoExpansion of Hematopoietic Stem- and Progenitor Cells from Cord Blood in Coculture with Mesenchymal Stroma Cells from Amnion, Chorion, Wharton's Jelly, Amniotic Fluid, Cord Blood, and Bone Marrow

Cited by 33 publications

References 15 publications

Optimizing autologous cell grafts to improve stem cell gene therapy

Optimizing autologous cell grafts to improve stem cell gene therapy

Modalities to Improve Cord Blood Engraftment

Comparison of serum granulocyte colony-stimulating factor levels between preterm and term births

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