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Biomedical subjects

Dieter Hoelzer

Publications and source records attributed to Dieter Hoelzer.

At least 73 records · Page 4Linked to original sources
PubMed2003

Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation.

Cytotoxic drugs mediate apoptotic tumor cell death by influencing key regulator proteins of programmed cell death. In clinical practice cytotoxic drug combinations are desired to potentiate tumor cell kill and to minimize side effects. Nevertheless, the molecular mechanisms underlying synergistic and antagonistic effects on tumor cells are still poorly understood. In order to elucidate these molecular mechanisms we established models of synergistic and antagonistic drug combinations within the same lymphoma cell lines. By combination index method we demonstrated that bendamustine in combination with either doxorubicin or mitoxantrone caused antagonistic effects on disruption of mitochondrial membrane potential as well as on the rate of apoptosis. In contrast the combination of bendamustine with cladribine acted synergistically on these parameters. By using the IC(50) (dosages causing 50% rate of apoptosis) the synergistic effect of the combination of bendamustine and cladribine was associated with an enhanced mitochondrial release of cytochrome c and Smac/DIABLO, by down-regulation of x-linked inhibitor of apoptosis (XIAP), cIAP1, Par-4 and Daxx as well as by a significantly increased activation of caspases-3, -6, -7, -8 and -9. At the same rate of apoptosis (IC(50)), the antagonistic combinations did not increase the release of cytochrome c or Smac/DIABLO, nor down-regulate the expression of XIAP, cIAP1, Par-4 and Daxx, nor increase the activation of caspases. The role of down-regulation of IAPs and of enforced caspase activation for synergism in this model was supported by the observation, that broad spectrum inhibition of caspases re-established expression of XIAP. Our study is the first to outline the molecular alterations caused by synergistic and antagonistic drug combinations within the same lymphoma cell model. The above described mechanisms were already assessable at a point where the effects of synergistic or antagonistic combinations could not yet be discriminated quantitatively by the level of apoptosis rate of the lymphoma cells.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Targeting of the N-terminal coiled coil oligomerization interface of BCR interferes with the transformation potential of BCR-ABL and increases sensitivity to STI571.

Translocations involving the abl locus on chromosome 9 fuses the tyrosine kinase c-ABL to proteins harboring oligomerization interfaces such as BCR or TEL, enabling these ABL-fusion proteins (X-ABL) to transform cells and to induce leukemia. The ABL kinase activity is blocked by the ABL kinase inhibitor STI571 which abrogates transformation by X-ABL. To investigate the role of oligomerization for the transformation potential of X-ABL and for the sensitivity to STI571, we constructed ABL chimeras with oligomerization interfaces of proteins involved in leukemia-associated translocations such as BCR, TEL, PML, and PLZF. We assessed the capacity of these chimeras to form high molecular weight (HMW) complexes as compared with p185(BCR-ABL). There was a direct relationship between the size of HMW complexes formed by these chimeras and their capacity to induce factor independence in Ba/F3 cells, whereas there was an inverse relationship between the size of the HMW complexes and the sensitivity to STI571. The targeting of the oligomerization interface of p185(BCR-ABL) by a peptide representing the coiled coil region of BCR reduced its potential to transform fibroblasts and increased sensitivity to STI571. Our results indicate that targeting of the oligomerization interfaces of the X-ABL enhances the effects of STI571 in the treatment of leukemia caused by X-ABL.

Animals↗
PubMed2003

Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia.

The tyrosine kinase inhibitor STI571 (imatinib) binds competitively to the adenosine triphosphate (ATP) binding site of the ABL kinase, thereby inhibiting auto- and substrate phosphorylation of the oncogenic protein BCR-ABL and preventing the activation of downstream signaling pathways. Comparative studies on leukemic cell samples obtained from chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patients before and after treatment with STI571 reported point mutations in resistant samples after a short time of therapy. The aim of this study was to determine whether patients with Ph+ ALL in whom resistance developed as a consequence of the Glu255Lys mutation already harbored this subclone prior to STI571 treatment. First, the migration pattern of cDNAs from 30 bone marrow samples from patients with Ph+ ALL was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Thereafter, detailed mutational analysis using genomic DNA was performed on initial STI571-naive bone marrow samples of 4 individuals with Ph+ ALL, for whom the mutation Glu255Lys in association with STI571 treatment had been shown. A 166-bp PCR fragment spanning from nucleotide (nt) 862 to nt 1027 was cloned, and 108 clones per sample were analyzed by direct sequencing. This more sensitive technique revealed the presence of the Glu255Lys mutation in 2 initial samples, one clone each. We identified for the first time the mutation Glu255Lys in STI571-naive leukemic samples of Ph+ ALL patients. The findings suggest that the mutation exists in a very small subpopulation of leukemic cells at the beginning of STI571 therapy.

Adult↗
PubMed2003

Comparison of TaqMan real-time PCR and p24 Elisa for quantification of in vitro HIV-1 replication.

In this study, TaqMan PCR was used to assess viral replication of HIV-1 infected cells in vitro. This PCR technique was compared with p24 ELISA as a standard method to monitor HIV-1 replication in cell culture. Hut78 T-lymphoblastoid cells were infected with different titres of HIV-1(IIIb) (MOI 0.05-0.0005). The course of HIV-1 replication was monitored by determination of p24 concentrations by ELISA in cell culture supernatants and by quantitation of HIV-1 gag RNA by TaqMan RT-PCR. Additionally, the number of HIV-1 proviral copies was assessed by TaqMan PCR. Monitoring of HIV-1 replication by p24 ELISA and TaqMan RT-PCR revealed comparable kinetics of infection. Both methods provided similar data on the exponential increase and on plateauing of HIV-1 replication. Furthermore, both methods were equally sensitive. However, a 7 log linearity of TaqMan HIV-1 gag PCR was demonstrated without dilution of the specimen, in contrast to p24 ELISA, where because of its narrow range of detectable p24 concentrations, sample dilution was necessary. Although determination of the number of proviral copies by TaqMan PCR does not measure HIV-1 replication, the kinetics of proviral copy number following in vitro inoculation of cells with HIV-1 was nearly the same as the kinetics of HIV-1 RNA copy numbers. In conclusion, TaqMan real-time RT-PCR was demonstrated as a reliable and sensitive tool to quantify and monitor HIV-1 replication in cell culture. It is suggested, therefore, that this technique be an alternative method to monitor HIV-1 replication in vitro.

Cell Line↗
PubMed2003

CD4+ CD56+ neoplasia: clinical and biological features with emphasis on cytotoxic drug-induced apoptosis and expression of sialyl Lewis X.

CD4+ CD56+ neoplasia is a rare malignancy of unclarified origin. So far only 57 cases have been reported. We characterized in detail a case of CD4+ CD56+ malignancy with special emphasis on apoptosis induced by cytotoxic drugs and expression of sialyl Lewis X (CD15s). The disease was diagnosed in a 73-year-old female presenting with skin involvement, generalized lymphadenopathy and bone marrow infiltration. Treatment with cladribine/mitoxantrone induced a short-lasting partial response and the patient died 6 months after diagnosis. The neoplastic cells expressed CD4, CD56, HLA-DR, and CD15s. PCR for the T-cell receptor gamma chain revealed a polyclonal amplification product. In situ hybridization for Epstein-Barr Virus (EBV) was negative. Cytotoxic granule-associated proteins were not detected, consistent with the observation that the cells did not mediate cytotoxic activity against several target cells. Apoptosis of the tumor cells was inducible by anthracyclines and cladribine but not with gemcitabine. Combinations of cladribine or gemcitabine with anthracyclines however, resulted in synergistic effects on apoptosis. Expression of CD15s on the CD56+ cells was three times higher than on CD56+ cells from healthy controls. The results demonstrate that the features of the present case is in accordance with the diagnosis of CD4+ CD56+ malignancy. This is the first report demonstrating increased CD15s expression on a CD4+ CD56+ neoplasia, possibly explaining the frequent occurrence of the disease in the skin.

Aged↗
PubMed2003

In AML cell lines Ara-C combined with purine analogues is able to exert synergistic as well as antagonistic effects on proliferation, apoptosis and disruption of mitochondrial membrane potential.

The pyrimidine analogue Ara-C and the purine analogues fludarabine and cladribine (2-CdA) are essential compounds in the treatment of acute myeloid leukemia (AML). Inhibition of cell proliferation and induction of apoptosis are the major mechanisms of cytotoxic agents to cause tumor cell death. Therefore, we studied whether Ara-C in combination with the purine analogues exerts synergistic or antagonistic effects on cell proliferation, phosphatidylserine exposure and disruption of mitochondrial membrane potential (MMP) in the AML cell lines HL60 and HEL. Furthermore, effects of the combination of Ara-C with bendamustine, a new bifunctional agent with alkylating activity and a purine nucleus, was investigated. Assessment by combination index analysis showed that Ara-C combined with fludarabine or bendamustine exhibited additive to antagonistic effects on inhibition of cell proliferation, induction of apoptosis as well as on disruption of mitochondrial membrane potential, independent of a simultaneous or consecutive (purine analogues before Ara-C) incubation schedule. In contrast, the combination of Ara-C with 2-CdA exclusively yielded synergistic effects. While inducing IC50 levels of apoptosis neither the antagonistic nor the synergistic drug combinations caused a specific expression pattern of apoptosis-associated proteins such as the pro- or antiapoptotic Bcl-2 family members, executioner caspases, IAPs (inhibitor of apoptosis proteins), proapoptotic Par-4, PARP, or p53. In conclusion, we here demonstrate that the in vitro efficacy of drug combinations containing Ara-C and purine analogues depends on the purine analogue applied, whereas incubation schedules or escalating dosages do not contribute to the synergistic effects.

Acute Disease↗
PubMed2003

Cloning and chromosomal characterization of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 gene (PFKFB3, iPFK2).

PFKFB (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) is a bifunctional enzyme that regulates the steady-state concentration of fructose-2,6-bisphosphate, which is a potent activator of the key regulatory enzyme of glycolysis, phosphofructokinase. PFKFB3 (iPFK2) is one of four tissue-specific PFKFB isozymes that have been identified to date. PFKFB3 also has been implicated in the high glycolytic rate of cancer cells that occurs despite adequate oxygen, a phenomenon known as the Warburg effect. We have isolated and characterized the human PFKFB3 genomic sequence, which spans a region of 32.5 kb and which has a single chromosomal locus. Determination of the exon-intron splice junctions established that PFKFB3 is encoded by 19 exons of which only 15 are normally expressed. Exon sizes range between 23 and 208 bp, the largest intron is 10,286 bp long. The full-length human PFKFB3 open reading frame is 4,675 bp long and encodes a 590 aa protein with a predicted molecular weight of 66.9 kDa and an isoelectric point of 8.64. Fluorescence in situ hybridization analysis localized the human PFKFB3 gene to chromosome 10p15.3-p15.2, and its locus is 3 million bp centromeric to PFKP, the platelet-type phosphofructokinase. PFKFB3 has been shown to be abundantly expressed in human tumors and its expression linked to long-standing observations concerning the apparent coupling of enhanced glycolysis and cell proliferation.

Amino Acid Sequence↗
PubMed2003

Cell lineage assignment of cytogenetic findings in acute lymphoblastic leukemia using combined immunomagnetic cell separation and chromosome preparation.

In acute lymphoblastic leukemia (ALL) abnormal karyotypes frequently constitute a minor part of the dividing cells, and the origin of metaphases in normal diploid cases remains obscure. We used a combination of immunomagnetic cell separation and chromosome preparation (ICSCP) to focus on the metaphases of interest and to assign the chromosome findings to CD19+ or CD7+ leukemia cells.

Adolescent↗
PubMed2002

Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease.

Graft versus host disease (GVHD) is an important problem following allogenic bone marrow transplantation (BMT). The beneficial effects of photochemotherapy with psoralens plus UVA irradiation (PUVA) have been described repeatedly; however, PUVA is limited by a wide range of unwanted effects. A novel improved form of UV-B phototherapy, narrowband UV-B, has been proven to be very effective in T-cell mediated dermatoses. Therefore, we investigated the effect of narrowband UV-B phototherapy (5 times per week) in 10 patients with cutaneous GVHD (grade 2-3) resistant to standard immunosuppressive drugs. It was tolerated well by all patients, and no side effects were observed. Skin lesions showed complete clearance in 7 out of 10 patients within 3 to 5 weeks. 3 patients showed significant improvement of GVHD. We suggest that narrowband UV-B phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD who already take high doses of immunosuppressive drugs.

Adult↗
PubMed2002

Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI).

BACKGROUND: Experimental studies suggest that transplantation of blood-derived or bone marrow-derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown. METHODS AND RESULTS: We randomly allocated 20 patients with reperfused acute myocardial infarction (AMI) to receive intracoronary infusion of either bone marrow-derived (n=9) or circulating blood-derived progenitor cells (n=11) into the infarct artery 4.3+/-1.5 days after AMI. Transplantation of progenitor cells was associated with a significant increase in global left ventricular ejection fraction from 51.6+/-9.6% to 60.1+/-8.6% (P=0.003), improved regional wall motion in the infarct zone (-1.5+/-0.2 to -0.5+/-0.7 SD/chord; P<0.001), and profoundly reduced end-systolic left ventricular volumes (56.1+/-20 mL to 42.2+/-15.1 mL; P=0.01) at 4-month follow-up. In contrast, in a nonrandomized matched reference group, left ventricular ejection fraction only slightly increased from 51+/-10% to 53.5+/-7.9%, and end-systolic volumes remained unchanged. Echocardiography revealed a profound enhancement of regional contractile function (wall motion score index 1.4+/-0.2 at baseline versus 1.19+/-0.2 at follow-up; P<0.001). At 4 months, coronary blood flow reserve was significantly (P<0.001) increased in the infarct artery. Quantitative F-18-fluorodeoxyglucose-positron emission tomography analysis revealed a significant (P<0.01) increase in myocardial viability in the infarct zone. There were no differences for any measured parameter between blood-derived or bone marrow-derived progenitor cells. No signs of an inflammatory response or malignant arrhythmias were observed. CONCLUSIONS: In patients with AMI, intracoronary infusion of autologous progenitor cells appears to be feasible and safe and may beneficially affect postinfarction remodeling processes.

Cells, Cultured↗
PubMed2002

AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor.

Acute myeloid leukemia (AML)-associated chromosomal translocations result in formation of chimeric transcription factors, such as PML/RARalpha, PLZF/RARalpha, and AML-1/ETO, of which the components are involved in regulation of transcription by chromatin modeling through histone acetylation/deacetylation. The leukemic differentiation block is attributed to deregulated transcription caused by these chimeric fusion proteins, which aberrantly recruit histone-deacetylase (HDAC) activity. One essential differentiation pathway blocked by the leukemic fusion proteins is the vitamin (Vit) D(3) signaling. Here we investigated the mechanisms by which the leukemic fusion proteins interfere with VitD(3)-induced differentiation. The VitD(3)-receptor (VDR) is, like the retinoid receptors RAR, retinoid X receptor, and the thyroid hormone receptor (TR), a ligand-inducible transcription factor. In the absence of ligand, the transcriptional activity of TR and RAR is silenced by recruitment of HDAC activity through binding to corepressors. In the presence of ligand, TR and RAR activate transcription by releasing HDAC activity and by recruiting histone-acetyltransferase activity. Here we report that VDR binds corepressors in a ligand-dependent manner and that inhibition of HDAC activity increases VitD(3) sensitivity of HL-60 cells. Nevertheless, the inhibition of HDAC activity is unable to overcome the block of VitD(3)-induced differentiation caused by PLZF/RARalpha expression. Here we demonstrate that the expression of the translocation products PML/RARalpha and PLZF/RARalpha impairs the localization of VDR in the nucleus by binding to VDR. Furthermore, the overexpression of VDR in U937 cells expressing AML-related translocation products completely abolishes the block of VitD(3)-induced differentiation. Taken together these data indicate that the AML-associated translocation products block differentiation not only by interfering with chromatin-modeling but also by sequestering factors involved in the differentiation signaling pathways, such as VDR in the VitD(3)-induced differentiation.

Cell Differentiation↗
PubMed2002

Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow.

Gene patterns of expression in purified CD34(+) bone marrow cells from 7 patients with low-risk myelodysplastic syndrome (MDS) and 4 patients with high-risk MDS were compared with expression data from CD34(+) bone marrow cells from 4 healthy control subjects. CD34(+) cells were isolated by magnetic cell separation, and high-density oligonucleotide microarray analysis was performed. For confirmation, the expression of selected genes was analyzed by real-time polymerase chain reaction. Class membership prediction analysis selected 11 genes. Using the expression profile of these genes, we were able to discriminate patients with low-risk from patients with high-risk MDS and both patient groups from the control group by hierarchical clustering (Spearman confidence). The power of these 11 genes was verified by applying the algorithm to an unknown test set containing expression data from 8 additional patients with MDS (3 at low risk, 5 at high risk). Patients at low risk could be distinguished from those at high risk by clustering analysis. In low-risk MDS, we found that the retinoic-acid-induced gene (RAI3), the radiation-inducible, immediate-early response gene (IEX1), and the stress-induced phosphoprotein 1 (STIP1) were down-regulated. These data suggest that CD34(+) cells from patients with low-risk MDS lack defensive proteins, resulting in their susceptibility to cell damage. In summary, we propose that gene expression profiling may have clinical relevance for risk evaluation in MDS at the time of initial diagnosis. Furthermore, this study provides evidence that in MDS, hematopoietic stem cells accumulate defects that prevent normal hematopoiesis.

Aged↗
PubMed2002

A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias.

The translocation (9;22) gives rise to the p190(Bcr-Abl) and p210(Bcr-Abl) tyrosine kinase proteins, considered sufficient for leukemic transformation. Philadelphia-positive (Ph(+)) acute leukemia patients failing to respond to initial induction therapy have a poor prognosis with few effective treatment options. Imatinib is an orally administered, potent inhibitor of the Bcr-Abl tyrosine kinase. We conducted a clinical trial in 56 patients with relapsed or refractory Ph(+) acute lymphoblastic leukemia (ALL; 48 patients) or chronic myelogenous leukemia in lymphoid blast crisis (LyBC; 8 patients). Imatinib was given once daily at 400 mg or 600 mg. Imatinib induced complete hematologic responses (CHRs) and complete marrow responses (marrow-CRs) in 29% of ALL patients (CHR, 19%; marrow-CR, 10%), which were sustained for at least 4 weeks in 6% of patients. Median estimated time to progression and overall survival for ALL patients were 2.2 and 4.9 months, respectively. CHRs were reported for 3 (38%) of the patients with LyBC (one sustained CHR). Grade 3 or 4 treatment-related nonhematologic toxicity was reported for 9% of patients; none of the patients discontinued therapy because of nonhematologic adverse reactions. Grade 4 neutropenia and thrombocytopenia occurred in 54% and 27% of patients, respectively. Imatinib therapy resulted in a clinically relevant hematologic response rate in relapsed or refractory Ph(+) acute lymphoid leukemia patients, but development of resistance and subsequent disease progression were rapid. Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib.

Adult↗
PubMed2002

Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571).

The Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia (Ph(+) ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph(+) ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n = 2) or no (n = 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median Bcr-Abl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 10(-4) in PB and below 10(-2) in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (< 10(-2)) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (139 vs 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies.

Antineoplastic Agents↗
PubMed2002

Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia.

We treated 45 adult patients with T-lymphoblastic lymphoma (T-LBL) (age range 15-61 years) with 2 protocols designed for adult acute lymphoblastic leukemia (ALL). An encouraging cure rate of 90% was recently reported for T-LBL in children treated with a similar approach. In our study, an 8-drug standard induction was administered over 8 weeks including prophylactic cranial (24 Gy) and mediastinal irradiation (24 Gy) followed by consolidation and reinduction therapy. At diagnosis, 91% of the 45 patients showed a mediastinal tumor and 40% had pleural/pericardial effusions; 73% of the patients had stage III/IV disease. Overall, 42 patients (93%) achieved a complete remission (CR), 2 patients (4%) achieved a partial remission, and 1 patient (2%) died during induction. In patients with stage I-III disease (n = 18) the CR rate was 100% compared with 89% in stage IV (n = 27). There were 15 patients who relapsed (36%) within 12 months. The majority of relapses (47%) occurred in the mediastinum (n = 7) despite mediastinal irradiation with 24 Gy in 6 out of 7 patients. The estimates for overall survival, continuous CR, and disease-free survival at 7 years are 51%, 65%, and 62%, respectively. Stage, age, lactate dehydrogenase, and all other parameters had no influence on achievement of CR or outcome. This study demonstrates in a large cohort of patients with adult T-LBL that a high CR rate and a favorable outcome can be achieved with an ALL-type regimen. Mediastinal recurrence was the major obstacle and further improvement by intensification of chemotherapy, increased dose of mediastinal irradiation (36 Gy), and extended indications for stem cell transplantation seem to be required.

Adolescent↗
PubMed2002

Coordination of cell growth in cocultures by a genetic proliferation control system.

Advanced cell culture systems such as organotypic cultures or stem cell expansion often involve cocultivation of two or more different cell types. A typical situation is the use of a feeder cell line that supports survival, growth or controls the differentiation status of primary cells. Unequal proliferation capacities result in unbalanced cell growth, such as the undesired expansion of immortalized cells at the expense of the primary cells. We utilized a genetic regulatory system to coordinate cell growth in cocultures. Proliferation control of a feeder cell line by a recombinant transcription factor was employed to prevent feeder cells from overgrowing cocultured stem cells, thereby avoiding premature media exhaustion. Relevant characteristic cell-surface proteins present on the parental feeder cell line were preserved. No special equipment was required and cell-type specific growth could be adjusted even during coculture. When compared to a conventional gamma-irradiation procedure, genetic proliferation control was superior with respect to ease of use, robustness, cell adherence, morphology and viability. The results demonstrate the applicability of genetic proliferation control to coordinate growth of different cell types in cocultures.

Cell Communication↗