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Results for “Resting Phase, Cell Cycle”

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PubMed1991

Intrinsic factors involved in vascular smooth muscle cell proliferation in hypertension.

The exaggerated response to growth factors of vascular smooth muscle cells from spontaneously hypertensive rats when compared to cells from normotensive control Wistar-Kyoto rats persists in culture, indicating an intrinsic/genetic defect. The time course of 3H-thymidine incorporation shows that synchronized vascular smooth muscle cells from spontaneously hypertensive rats start to synthesize new DNA earlier after mitogenic stimulation than cells from normotensive rats. Flow cytometry demonstrates that in cell populations growing in 10% calf serum for three d there is a higher proportion of cells from spontaneously hypertensive rats in the S phase of the cell cycle. The same proportions in the G2 + M phase of growing, as well as synchronized cells from normotensive and hypertensive rats indicate no difference in polyploidy. Forward light scatter analysis reveals no difference in cell size. These results suggest that the growth kinetic of vascular smooth muscle cells from normotensive and spontaneously hypertensive rats are different. Since the defect seems to be in the prereplicative phase of the cell cycle susceptible to regulation by extrinsic factors, we studied the effect of the calmodulin inhibitor, W-7, on DNA synthesis. The comparable IC50 of W-7 to inhibit cell growth of vascular smooth muscle cells of both origins indicates that the defect may not be due only to calmodulin, and furthermore suggests the involvement of a previously-reported calmodulin activator in hypertension.

Animals↗

PubMed1999

p53 does not control the spindle assembly cell cycle checkpoint but mediates G1 arrest in response to disruption of microtubule system.

p53 plays a critical role as a tumour-suppressor in restricting the proliferation of damaged cells, thus preventing formation of genetically altered cell clones. Its inactivation leads, in particular, to accumulation of polyploid and aneuploid cells. To elucidate the role of p53 in control of chromosome number, we analysed its participation in the cell cycle checkpoints controlling: (1) spindle assembly; and (2) G1-to-S transitions in cells with disintegrated microtubule cytoskeleton. Treatment with 8-10 ng/ml of colcemid causing no visible destruction of the spindle leads to arrest of metaphase-to-anaphase transition in both p53-positive and p53-negative murine fibroblasts, as well as in p53-positive REF52 cells and their counterparts (where the p53 function was inactivated by transduction of dominant-negative p53 fragment). Furthermore, p53-positive and p53-defective rodent and human cells showed no significant difference in kinetics of metaphase-to-interphase transitions in cultures treated with high colcemid doses preventing spindle formation. These data argue against the hypothesis that p53 is a key component of the spindle-assembly checkpoint. However, p53 mediates activation of the G1 checkpoint in response to depolymerization of microtubules in interphase cells. Treatment of synchronized G0/G1 cells with colcemid causes arrest of G1-to-S transition. Inactivation of the p53 function by transduction of dominant-negative p53 fragment abolishes the G1 checkpoint that prevents entry into S phase of cells with disrupted microtubules. Transduction of kinase-defective dominant-negative c- raf mutant or application of PD 098059, a specific inhibitor of MEK1, also abrogates the G1 cell cycle arrest in cells with disintegrated microtubule system. It seems that Raf-MAP-kinase signalling pathways are responsible for p53 activation induced by depolymerization of microtubules.

Animals↗

PubMed2001

Correlating cell cycle with apoptosis in a cell line expressing a tandem green fluorescent protein substrate specific for group II caspases.

BACKGROUND: We describe a rapid flow cytometric assay that correlates cell cycle with apoptotic cell death in a cell line expressing a tandem green fluorescent protein (GFP). METHODS: A Jurkat cell line was transfected with a gene construct coding for constitutive expression of a tandem GFP molecule carrying a consensus cleavage site (DEVD) for group II caspases (C-2-Y). Cells were treated with CD95 antibody (Ab), then incubated with annexin V-phycoerythrin (PE), propidium iodide (PI), and Hoechst 33342. RESULTS: After CD95 treatment, the C-2-Y cell line had twice the number of nonapoptotic cells compared with both control cell lines. This proportion of viable, nonapoptotic cells after treatment was unaffected by the level of GFP (DEVD) expression in the cells, as confirmed by sorted populations. The early apoptotic cells in the C-2-Y cell line had an increased G0-G1 phase population compared with the control cell lines. CONCLUSIONS: Apoptosis is delayed in the C-2-Y cell line and the early apoptotic cells have a higher G0-G1 cell cycle frequency. The artificial substrate competes with the natural substrate(s), thereby slowing the apoptotic process. The expression level of DEVD-GFP does not alter the delayed induction of apoptosis. Caspase activation occurs prior to phosphatidylserine translocation.

Antibodies, Monoclonal↗

PubMed2002

Prointerleukin-16 contains a functional CcN motif that regulates nuclear localization.

The immunomodulatory cytokine interleukin-16 (IL-16) represents the secreted C-terminus of a larger precursor, pro-IL-16. Following cleavage by caspase 3, the residual N-terminal domain translocates into the nucleus, inducing G(0)/G(1) cell cycle arrest. We have previously identified a classical bipartite nuclear localization sequence (NLS) in the N-terminal domain of pro-IL-16. We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. This is the first description of a functional CcN motif in a cytokine precursor.

Active Transport, Cell Nucleus↗

PubMed1996

Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice.

Recently, the ligand for the Mpl receptor (ML) was identified to be thrombopoietin, the principal regulator of megakaryocytopoiesis and thrombopoiesis. We examined the effects of ML, as a single factor or in combinations with early acting factors such as steel factor (SF), interleukin (IL)-3, IL-1, IL-6, and granulocyte colony-stimulating factor (G-CSF), on colony formation from primitive progenitors of mice. Cells enriched for cell cycle dormant primitive progenitors were isolated from bone marrow cells of 5-fluorouracil (5-FU)-treated mice by a combination of Nycodenz density gradient separation, immunomagnetic selection for lineage-negative cells, and fluorescence-activated cell sorter (FACS) sorting for Ly-6A/E+Kit+ cells. ML, in the presence of erythropoietin, could support the formation of only a few megakaryocyte colonies. However, ML acted synergistically with SF or IL-3 to support the formation of multiple types of hematopoietic colonies including multilineage colonies. Effects of the combination of ML and SF on multipotential progenitors were not mediated through other cells, as demonstrated by micromanipulation of individual progenitors. In suspension culture, the combination of ML and SF increased the number of multipotential progenitors. ML also acted synergistically with IL-11, IL-6, or G-CSF to support colony formation in serum-containing, but not in serum-free, cultures. However, the multilineage colony formation seen in serum-containing culture was completely abrogated by addition of ACK2, a neutralizing antibody to Kit protein. Serial observation (mapping studies) of colony development from multipotential progenitors suggested that ML triggers the cell division of dormant progenitors. Based on these observations, we propose that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G0 period.

Animals↗

PubMed1996

G0/G1 growth arrest mediated by a region encompassing the basic leucine zipper (bZIP) domain of the Epstein-Barr virus transactivator Zta.

The Epstein-Barr virus (EBV) immediate early transactivator Zta is a basic leucine zipper (bZIP) transcription factor that causes G0/G1 cell cycle arrest through induction of the tumor suppressor protein, p53, and the cyclin-dependent kinase inhibitors, p21 and p27 (Cayrol, C., and Flemington, E. K. (1996) EMBO J. 15, 2748-2759). Here, we report a genetic analysis of Zta-mediated G0/G1 growth arrest and p21 induction. The majority of the Zta transactivation domain can be deleted (ZDelta1-128) without significantly affecting the ability of Zta to elicit growth arrest. A larger amino-terminal deletion (ZDelta1-167) abrogates the ability of Zta to inhibit proliferation, mapping the growth-inhibitory domain to a carboxyl-terminal region encompassing the bZIP domain (amino acids 128-245). The integrity of the bZIP domain is required for growth suppression since a two-amino acid mutant which is defective for homodimerization, fails to induce cell cycle arrest. Western blot analysis of p21 expression in cells expressing Zta mutants reveals that the ability of Zta mutants to cause G0/G1 growth arrest is intimately related to their capacity to induce p21 expression. Together, these data demonstrate that a carboxyl-terminal region of Zta that includes the bZIP domain is sufficient to mediate G0/G1 growth arrest and p21 induction.

Blotting, Western↗

PubMed1999

Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis.

Our previously performed experiments clearly showed a significant VDR-mediated growth inhibitory effect of 1,25-dihydroxyvitamin D3 and its synthetic analogs in a variety of human cancer cells including human colon and breast cancer, soft tissue sarcoma, and malignant melanoma cell lines. The mechanisms by which 1, 25-dihydroxyvitamin D3 and its synthetic analogs growth inhibit human cancer cells is poorly elucidated. The exposure of human colon cancer cells HT-29 to 1,25-dihydroxyvitamin D3 or its analog, 1alpha, 25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-nor-choleca lci ferol (Ro 25-6760), at the 10(-6) M concentration resulted in significant growth inhibition with induction of the apoptotic process after three days of treatment detected by TUNEL assay and agarose gel electrophoresis of DNA. As a logical link with DNA fragmentation analyses and TUNEL assay, cleavage of the 116 kDa PARP protein was accompanied by the appearance of a characteristic 85 kDa fragment of PARP in a population of floating cells after both treatments. The results of cell cycle analysis showed a G0/G1 phase block after three days of administration of either compound when compared with untreated cells. On day 4, G0/G1 cell cycle arrest remained on the same level in comparison with control. Paralleling the G0/G1 phase block, was a notable decrease in the number of cells in the S phase which also became significant after three days of treatment. The results of these experiments show that the newly developed 19-nor synthetic vitamin D3 analog, Ro 25-6760, as well as 1, 25-dihydroxyvitamin D3, induced the expression of p21waf1, resulted in a significant G1/G0 cell cycle arrest leading to impressive growth inhibition and induction of apoptosis associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) showing a possible involvement of apoptosis-specific activation of the ICE/CED-3 proteolitic pathway.

Antineoplastic Agents↗

PubMed2000

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G(2)/M transit and do not reenter G(0).

An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G(1) fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G(0)/G(1) and S/G(2)/M. Interestingly, the G(0) cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle-associated change in in vivo stem cell homing, the cultured G(0)/G(1) and S/G(2)/M CD34(+) CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor beta(1) that increased the G(0)/G(1) fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle-associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo-manipulated grafts. (Blood. 2000;96:4185-4193)

Animals↗

PubMed2005

Artepillin C in Brazilian propolis induces G(0)/G(1) arrest via stimulation of Cip1/p21 expression in human colon cancer cells.

Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis.

Blotting, Northern↗

PubMed1997

Evidence for a mammalian Nim1-like kinase pathway acting at the G0-1/S transition.

In fission yeast the Nim1 kinase phosphorylates and inactivates the cdc2-inhibitory Weel tyrosine kinase. In addition, Nim1 is necessary for an efficient cellular response to nutritional starvation leading to cell cycle arrest in G1. Given the remarkable evolutionary conservation of the cell cycle regulatory mechanism we have investigated the effect of Nim1 expression on the control of the mammalian cell cycle using a plasmid microinjection approach. In synchronised IMR90 human fibroblasts, expression of Nim1 strongly inhibited entry into S-phase. This effect was dependent on the catalytic activity of Nim1 and did not require its regulatory domain. Furthermore we show that co-expression of human Wee1 kinase reverted the inhibitory effect, indicating that Nim1 was acting in a Wee1-dependent manner. These results provide evidence for the existence of a Nim1-like kinase pathway acting at the G0-1/S transition in human cells.

Fibroblasts↗

PubMed2003

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo.

The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959+/-0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G(1)/G(0) cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

Adrenomedullin↗

PubMed2003

YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway.

This study was designed to investigate the effect of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, in human umbilical vein endothelial cells (HUVECs) proliferation and its underlying mechanism. YC-1 at a range of concentrations (5-50 microM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a dose- and time-dependent manner. YC-1 was not cytotoxic at these concentrations. [3H]thymidine incorporation and flow cytometry analyses revealed that YC-1 treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Western blot analysis demonstrated that YC-1 (5-50 microM) increased the levels of cyclin-dependent kinase (CDK)-inhibitory proteins (CKIs), p21 and p27, but did not induce any significant changes of cyclins and CDKs. In the YC-1-treated HUVEC, the formation of CDK2-p21 complex, but not CDK2-p27 complex, was increased and the assayable CDK2 kinase activity was decreased. These changes were in a dose-dependent manner. In contrast, the formations of CDK4-p21 and CDK4-p27 complex were slightly increased and the assayable CDK4 kinase activity was slightly decreased (if there were any changes). Pretreatment with guanylyl cyclase inhibitors, 1H-(1,2,4)oxadiazolo[4,3-a]quinozalin-1-one (ODQ) and methylene blue, inhibited the YC-1-induced increase of cyclic GMP level, but did not change significantly the magnitude of the YC-1-induced inhibition of thymidine incorporation and cell number in HUVEC. These results indicate that YC-1-induced cell cycle arrest in HUVEC occurred when the cyclin-CDK system was inhibited just as p21 and p27 protein levels were augmented. This YC-1-induced antiproliferation effect in HUVEC is via a cyclic GMP-independent pathway.

Cell Division↗

PubMed2004

Mammalian Cdh1/Fzr mediates its own degradation.

The Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase mediates degradation of cell cycle proteins during mitosis and G1. Cdc20/Fzy and Cdh1/Fzr are substrate-specific APC/C activators. The level of mammalian Cdh1 is high in mitosis, but it is inactive and does not bind the APC/C. We show that when Cdh1 is active in G1 and G0, its levels are considerably lower and almost all of it is APC/C associated. We demonstrate that Cdh1 is subject to APC/C-specific degradation in G1 and G0, and that this degradation depends upon two RXXL-type destruction boxes. We further demonstrate that addition of Cdh1 to Xenopus interphase extracts, which have an inactive APC/C, activates it to degrade Cdh1. These observations indicate that Cdh1 mediates its own degradation by activating the APC/C to degrade itself. Elevated levels of Cdh1 are deleterious for cell cycle progression in various organisms. This auto-regulation of Cdh1 could thus play a role in ensuring that the level of Cdh1 is reduced during G1 and G0, allowing it to be switched off at the correct time.

Amino Acid Motifs↗

PubMed1999

NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition.

Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation, transformation, and tumor development. We provide evidence for a direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred activation by NF-kappaB as well as by growth factors. Both levels and kinetics of cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover, inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1-associated kinase activity and resulted in delayed phosphorylation of the retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell cycle progression of T47D cells expressing an NF-kappaB superrepressor (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus, NF-kappaB contributes to cell cycle progression, and one of its targets might be cyclin D1.

3T3 Cells↗

PubMed1998

Activation of Src family members is not required for the platelet-derived growth factor beta receptor to initiate mitogenesis.

The basal activity of Src family kinases is readily detectable throughout the cell cycle and increases by two- to fivefold upon acute stimulation of cells with growth factors such as platelet-derived growth factor. Previous reports have demonstrated a requirement for Src activity for the G1/S and G2/M transitions. With a chimeric alpha-beta PDGF receptor (PDGFR) expressed in fibroblasts, we have investigated the importance of the PDGF-mediated increase in Src activity at the G0/G1 transition for subsequent cell cycle events. A mutant PDGFR chimera that was not able to detectably associate with or activate Src was compromised in its ability to mediate tyrosine phosphorylation of receptor-associated signaling molecules and initiated a submaximal activation of Erk. In contrast to these early cell cycle events, later responses such as entry of cells into S phase and cell proliferation proceeded normally when Src activity did not increase following acute stimulation with PDGF. We conclude that the initial burst of Src activity is required for efficient tyrosine phosphorylation of receptor-associated proteins such as PLCgamma, RasGAP, Shc, and SHP-2 and for maximal activation of Erk. Surprisingly, these events are not required for PDGF-dependent cell proliferation. Finally, later cell cycle events do not require that Src be activated at the G0/G1 transition and leave open the possibility that events such as the G1/S transition require the basal Src activity and/or activation of Src at later times in G1.

Amino Acid Substitution↗

PubMed1999

Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is associated with downregulation of bcl-2 expression.

Dietary polyunsaturated fatty acids (PUFAs) have been reported as a potential group of natural products which modulate tumor cell growth. In present study, eicosapentaenoic acid (EPA) was found to inhibit proliferation of human leukemic HL-60 and K-562 cells in vitro. EPA arrested cell cycle progression at G0/G1 phase, and induced necrosis in both HL-60 and K-562 cells. However, EPA induced apoptosis only in HL-60 but not K-562 cells. Also, bcl-2 protein expression was downregulated in much greater extent than that of bax showing that depression of bcl-2 might be an important step during the EPA-induced apoptosis in HL-60 cells.

Apoptosis↗

PubMed1997

The growth inhibitory effect of conjugated linoleic acid on MCF-7 cells is related to estrogen response system.

Conjugated linoleic acid (CLA) has been shown to have a direct oncostatic action on MCF-7 human breast cancer cells in culture. However, the mechanism involved is not fully elucidated. In this study we have examined whether the inhibitor action is related to the estrogen responsiveness of MCF-7 cells. Our results demonstrate that CLA selectively inhibits proliferation of ER positive MCF-7 cells as compared with ER negative MDA-MB-231 cells. Cell cycle studies indicated that a higher percentage of CLA treated MCF-7 cells remained in the G0/G1 phase as compared to control and those treated with linoleic acid (LA). CLA also inhibited expression of c-myc in MCF-7 cells. These results demonstrate that CLA may inhibit MCF-7 cell growth by interfering with the hormone regulated mitogenic pathway. We are reporting for the first time the involvement of CLA, a dietary factor, in the regulation of hormone mediated mitogenic pathways in ER positive breast cancer cell proliferation in vitro.

Anticarcinogenic Agents↗

PubMed2005

Cycling G1 CD34+/CD38+ cells potentiate the motility and engraftment of quiescent G0 CD34+/CD38-/low severe combined immunodeficiency repopulating cells.

The mechanism of human stem cell expansion ex vivo is not fully understood. Furthermore, little is known about the mechanisms of human stem cell homing/repopulation and the role that differentiating progenitor cells may play in these processes. We report that 2- to 3-day in vitro cytokine stimulation of human cord blood CD34(+)-enriched cells induces the production of short-term repopulating, cycling G1 CD34(+)/CD38(+) cells with increased matrix metalloproteinase (MMP)-9 secretion as well as increased migration capacity to the chemokine stromal cell-derived factor-1 (SDF-1) and homing to the bone marrow of irradiated nonobese diabetic severe/combined immunodeficiency (NOD/SCID) mice. These cycling G1 cells enhance SDF-1-mediated in vitro migration and in vivo homing of quiescent G0 CD34(+) cells, which is partially abrogated after inhibition of MMP-2/-9 activity. Moreover, the engraftment potential of quiescent G0 SCID repopulating cells (SRCs) is also increased by the cycling G1 CD34(+)/CD38(+) cells. This effect is significantly abrogated after incubation of cycling G1 cells with a neutralizing anti-CXCR4 antibody. Our data suggest synergistic interactions between accessory cycling G1 CD34(+)/CD38(+) committed progenitor cells and quiescent, primitive G0 CD34(+)/CD38(-/low) SRC/stem cells, the former increasing the motility and engraftment potential of the latter, partly via secretion of MMP-9.

ADP-ribosyl Cyclase 1↗