Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential.
Hematopoietic stem cell (HSC) engraftment is a multistep process involving HSC homing to bone marrow,self-renewal,proliferation,and differentiation to mature blood cells. Here,we show that loss of p190-B RhoGTPase activating protein,a negative regulator of Rho GTPases,results in enhanced long-term engraftment during serial transplantation. This effect is associated with maintenance of functional HSC-enriched cells. Furthermore,loss of p190-B led to marked improvement of HSC in vivo repopulation capacity during ex vivo culture without altering proliferation and multilineage differentiation of HSC and progeny. Transcriptional analysis revealed that p190-B deficiency represses the up-regulation of p16(Ink4a) in HSCs in primary and secondary transplantation recipients,providing a possible mechanism of p190-B-mediated HSC functions. Our study defines p190-B as a critical transducer element of HSC self-renewal activity and long-term engraftment,thus suggesting that p190-B is a target for HSC-based therapies requiring maintenance of engraftment phenotype.
View Publication
产品类型：
产品号#：
09600
09650
产品名：
StemSpan™ SFEM
StemSpan™ SFEM
文献
Yu H et al. (FEB 2006)
Blood 107 3 1200--6
Hematopoietic stem cell exhaustion impacted by p18 INK4C and p21 Cip1/Waf1 in opposite manners.
Transplantation-associated stress can compromise the hematopoietic potential of hematopoietic stem cells (HSCs). As a consequence,HSCs may undergo exhaustion" in serial transplant recipients�
View Publication
产品类型：
产品号#：
产品名：
文献
Farese AM et al. (JAN 1996)
Blood 87 2 581--91
Acceleration of hematopoietic reconstitution with a synthetic cytokine (SC-55494) after radiation-induced bone marrow aplasia.
The synthetic cytokine (Synthokine) SC-55494 is a high-affinity interleukin-3 (IL-3) receptor ligand that stimulates greater in vitro multilineage hematopoietic activity than native IL-3,while inducing no significant increase in inflammatory activity relative to native IL-3. The aim of this study was to investigate the in vivo hematopoietic response of rhesus monkeys receiving Synthokine after radiation-induced marrow aplasia. Administration schedule and dose of Synthokine were evaluated. All animals were total-body irradiated (TBI) with 700 cGy 60Co gamma radiation on day 0. Beginning on day 1,cohorts of animals (n = 5) received Synthokine subcutaneously (SC) twice daily with 25 micrograms/kg/d or 100 micrograms/kg/d for 23 days or 100 micrograms/kg/d for 14 days. Control animals (n = 9) received human serum albumin SC once daily at 15 micrograms/kg/d for 23 days. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (NEUT; absolute neutrophil count [ANC] textless 500/microL) and thrombocytopenia (THROM; platelet count textless 20,000/microL) were assessed. Synthokine significantly (P textless .05) reduced the duration of THROM versus the HSA-treated animals regardless of dose or protocol length. The most striking reduction was obtained in the animals receiving 100 micrograms/kg/d for 23 days (THROM = 3.5 v 12.5 days in HSA control animals). Although the duration of NEUT was not significantly altered,the depth of the nadir was significantly lessened in all animal cohorts treated with Synthokine regardless of dose versus schedule length. Bone marrow progenitor cell cultures indicated a beneficial effect of Synthokine on the recovery of granulocyte-macrophage colony-forming units that was significantly higher at day 24 post-TBI in both cohorts treated at 25 and 100 micrograms/kg/d for 23 days relative to the control animals. Plasma pharmacokinetic parameters were evaluated in both normal and irradiated animals. Pharmacokinetic analysis performed in irradiated animals after 1 week of treatment suggests an effect of repetitive Synthokine schedule and/or TBI on distribution and/or elimination of Synthokine. These data show that the Synthokine,SC55 94,administered therapeutically post-TBI,significantly enhanced platelet recovery and modulated neutrophil nadir and may be clinically useful in the treatment of the myeloablated host.
View Publication
产品类型：
产品号#：
04436
04064
04100
04230
04236
04431
04434
04444
04464
04531
04535
04545
04536
04564
04035
04330
04034
04044
04435
04445
04534
04544
04437
04447
产品名：
MethoCult™SF H4436
入门套件的MethoCult™H4034优化
MethoCult™H4100
MethoCult™H4230
MethoCult™SF H4236
MethoCult™H4431
MethoCult™H4434经典
MethoCult™H4434经典
入门套件为MethoCult™H4434经典
MethoCult™H4531
MethoCult™H4535富集无EPO
MethoCult™ H4535 Enriched，不含EPO
MethoCult™SF H4536
入门套件MethoCult™H4534经典无EPO
MethoCult™H4035 Optimum无EPO
MethoCult™H4330
MethoCult™H4034 Optimum
MethoCult™H4034 Optimum
MethoCult™H4435富集
MethoCult™H4435富集
MethoCult™H4534经典无EPO
MethoCult™H4534经典无EPO
MethoCult™表达
MethoCult™表达
文献
J. Lam et al. (JUN 2018)
Nature communications 9 1 2418
miR-143/145 differentially regulate hematopoietic stem and progenitor activity through suppression of canonical TGFbeta$ signaling.
Expression of miR-143 and miR-145 is reduced in hematopoietic stem/progenitor cells (HSPCs) of myelodysplastic syndrome patients with a deletion in the long arm of chromosome 5. Here we show that mice lacking miR-143/145 have impaired HSPC activity with depletion of functional hematopoietic stem cells (HSCs),but activation of progenitor cells (HPCs). We identify components of the transforming growth factor beta$ (TGFbeta$) pathway as key targets of miR-143/145. Enforced expression of the TGFbeta$ adaptor protein and miR-145 target,Disabled-2 (DAB2),recapitulates the HSC defect seen in miR-143/145-/- mice. Despite reduced HSC activity,older miR-143/145-/- and DAB2-expressing mice show elevated leukocyte counts associated with increased HPC activity. A subset of mice develop a serially transplantable myeloid malignancy,associated with expansion of HPC. Thus,miR-143/145 play a cell context-dependent role in HSPC function through regulation of TGFbeta$/DAB2 activation,and loss of these miRNAs creates a preleukemic state.
View Publication
产品类型：
产品号#：
03434
03444
产品名：
MethoCult™GF M3434
MethoCult™GF M3434
文献
Jing J et al. ( 2012)
Molecular cancer therapeutics 11 3 720--729
Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212.
The MEK1 and MEK2 inhibitor GSK1120212 is currently in phase II/III clinical development. To identify predictive biomarkers,sensitivity to GSK1120212 was profiled for 218 solid tumor cell lines and 81 hematologic malignancy cell lines. For solid tumors,RAF/RAS mutation was a strong predictor of sensitivity. Among RAF/RAS mutant lines,co-occurring PIK3CA/PTEN mutations conferred a cytostatic response instead of a cytotoxic response for colon cancer cells that have the biggest representation of the comutations. Among KRAS mutant cell lines,transcriptomics analysis showed that cell lines with an expression pattern suggestive of epithelial-to-mesenchymal transition were less sensitive to GSK1120212. In addition,a proportion of cell lines from certain tissue types not known to carry frequent RAF/RAS mutations also seemed to be sensitive to GSK1120212. Among these were breast cancer cell lines,with triple negative breast cancer cell lines being more sensitive than cell lines from other breast cancer subtypes. We identified a single gene DUSP6,whose expression was associated with sensitivity to GSK1120212 and lack of expression associated with resistance irrelevant of RAF/RAS status. Among hematologic cell lines,acute myeloid leukemia and chronic myeloid leukemia cell lines were particularly sensitive. Overall,this comprehensive predictive biomarker analysis identified additional efficacy biomarkers for GSK1120212 in RAF/RAS mutant solid tumors and expanded the indication for GSK1120212 to patients who could benefit from this therapy despite the RAF/RAS wild-type status of their tumors.
View Publication
产品类型：
产品号#：
产品名：
文献
Pino CJ et al. (FEB 2013)
Nephrology,dialysis,transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 28 2 296--302
Cell-based approaches for the treatment of systemic inflammation.
Acute and chronic solid organ failures are costly disease processes with high mortality rates. Inflammation plays a central role in both acute and chronic organ failure,including heart,lung and kidney. In this regard,new therapies for these disorders have focused on inhibiting the mediators of inflammation,including cytokines and free radicals,with little or no success in clinical studies. Recent novel treatment strategies have been directed to cell-based rather than mediator-based approaches,designed to immunomodulate the deleterious effects of inflammation on organ function. One approach,cell therapy,replaces cells that were damaged in the acute or chronic disease process with stem/progenitor technology,to rebalance excessive inflammatory states. As an example of this approach,the use of an immunomodulatory role of renal epithelial progenitor cells to treat acute renal failure (ARF) and multiorgan failure arising from acute kidney injury is reviewed. A second therapeutic pathway,cell processing,does not incorporate stem/progenitor cells in the device,but rather biomimetic materials that remove and modulate the primary cellular components,which promote the worsening organ tissue injury associated with inflammation. The use of an immunomodulating leukocyte selective cytopheretic inhibitory device is also reviewed as an example of this cell processing approach. Both of these unconventional strategies have shown early clinical efficacy in pilot clinical trials and may transform the therapeutic approach to organ failure disorders.
View Publication
Yamamizu K et al. (DEC 2013)
Stem Cell Reports 1 6 545--559
Identification of Transcription Factors for Lineage-Specific ESC Differentiation
A network of transcription factors (TFs) determines cell identity,but identity can be altered by overexpressing a combination of TFs. However,choosing and verifying combinations of TFs for specific cell differentiation have been daunting due to the large number of possible combinations of 2,000 TFs. Here,we report the identification of individual TFs for lineage-specific cell differentiation based on the correlation matrix of global gene expression profiles. The overexpression of identified TFs-Myod1,Mef2c,Esx1,Foxa1,Hnf4a,Gata2,Gata3,Myc,Elf5,Irf2,Elf1,Sfpi1,Ets1,Smad7,Nr2f1,Sox11,Dmrt1,Sox9,Foxg1,Sox2,or Ascl1-can direct efficient,specific,and rapid differentiation into myocytes,hepatocytes,blood cells,and neurons. Furthermore,transfection of synthetic mRNAs of TFs generates their appropriate target cells. These results demonstrate both the utility of this approach to identify potent TFs for cell differentiation,and the unanticipated capacity of single TFs directly guides differentiation to specific lineage fates.
View Publication
EasySep™小鼠TIL（CD45）正选试剂盒
文献
产品手册T Cell Reagents for Your Cellular Therapy Research
产品手册Worksheet for Proficiency Testing with Frozen Samples (French)
技术公告The Colony-Forming Cell (CFC) Assay for Cord Blood
产品手册NeuroCult™: Reagents for Brain Tumor Stem Cell Research
