Editing Granulocyte colony-stimulating factor

{{Short description|Mammalian protein found in humans}}
{{distinguish|granulocyte-macrophage colony-stimulating factor}}
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{{Infobox_gene}}

'''Granulocyte colony-stimulating factor''' ('''G-CSF''' or '''GCSF'''), also known as '''colony-stimulating factor 3''' ('''CSF 3'''), is a [[glycoprotein]] that stimulates the [[bone marrow]] to produce [[granulocyte]]s and [[stem cell]]s and release them into the [[bloodstream]].<ref name="pmid25915812">{{cite journal | vauthors = Deotare U, Al-Dawsari G, Couban S, Lipton JH | title = G-CSF-primed bone marrow as a source of stem cells for allografting: revisiting the concept | journal = Bone Marrow Transplantation | volume = 50 | issue = 9 | pages = 1150–1156 | date = September 2015 | pmid = 25915812 | doi = 10.1038/bmt.2015.80 | s2cid = 20774089 | doi-access =  }}</ref><ref name="pmid27943116">{{cite journal | vauthors = Tay J, Levesque JP, Winkler IG | title = Cellular players of hematopoietic stem cell mobilization in the bone marrow niche | journal = International Journal of Hematology | volume = 105 | issue = 2 | pages = 129–140 | date = February 2017 | pmid = 27943116 | doi = 10.1007/s12185-016-2162-4 | doi-access = free }}</ref>

Functionally, it is a [[cytokine]] and [[hormone]], a type of [[colony-stimulating factor]], and is produced by a number of different [[tissue (biology)|tissues]]. The [[pharmaceutical drug|pharmaceutical]] analogs of naturally occurring G-CSF are called [[filgrastim]] and [[lenograstim]].

G-CSF also stimulates the survival, proliferation, differentiation, and function of [[neutrophil precursor]]s and mature [[neutrophil]]s.

== Biological function ==
G-CSF is produced by [[endothelium]], [[macrophage]]s, and a number of other [[immune system|immune]] cells. The natural human glycoprotein exists in two forms, a 174- and 177-[[amino acid|amino-acid]]-long [[protein]] of molecular weight 19,600&nbsp;grams per [[Mole (unit)|mole]]. The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by [[recombinant DNA]] (rDNA) technology.<ref name=":0">{{cite journal | vauthors = Bendall LJ, Bradstock KF | title = G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent | journal = Cytokine & Growth Factor Reviews | volume = 25 | issue = 4 | pages = 355–367 | date = August 2014 | pmid = 25131807 | doi = 10.1016/j.cytogfr.2014.07.011 | doi-access = free }}</ref>

;White blood cells: The [[Granulocyte colony-stimulating factor receptor|G-CSF-receptor]] is present on precursor cells in the [[bone marrow]], and, in response to stimulation by G-CSF, initiates proliferation and [[Cellular differentiation|differentiation]] into mature [[granulocyte]]s. G-CSF stimulates the survival, proliferation, differentiation, and function of [[neutrophil precursor]]s and mature [[neutrophil]]s. G-CSF regulates them using [[JAK-STAT signaling pathway|Janus kinase (JAK)/signal transducer and activator of transcription (STAT)]] and Ras/[[mitogen-activated protein kinase]] (MAPK) and [[phosphatidylinositol 3-kinase]] (PI3K)/[[protein kinase B]] (Akt) signal transduction pathway.{{citation needed|date=February 2024}}

;Hematopoietic System: G-CSF is also a potent inducer of [[hematopoietic stem cell]] (HSC) mobilization from the bone marrow into the bloodstream, although it has been shown that it does not directly affect the hematopoietic progenitors that are mobilized.<ref name="pmid11953662">{{cite journal | vauthors = Thomas J, Liu F, Link DC | title = Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor | journal = Current Opinion in Hematology | volume = 9 | issue = 3 | pages = 183–189 | date = May 2002 | pmid = 11953662 | doi = 10.1097/00062752-200205000-00002 | s2cid = 5774130 }}</ref>

;Neurons: G-CSF can also act on neuronal cells as a neurotrophic factor. Indeed, its receptor is expressed by neurons in the brain and spinal cord. The action of G-CSF in the central nervous system is to induce [[neurogenesis]], to increase the [[neuroplasticity]] and to counteract [[apoptosis]].<ref name="pmid16007267">{{cite journal | vauthors = Schneider A, Krüger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassler N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A, Kuhn HG, Schäbitz WR | title = The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis | journal = The Journal of Clinical Investigation | volume = 115 | issue = 8 | pages = 2083–2098 | date = August 2005 | pmid = 16007267 | pmc = 1172228 | doi = 10.1172/JCI23559 }}</ref><ref name="pmid18835867">{{cite journal | vauthors = Pitzer C, Krüger C, Plaas C, Kirsch F, Dittgen T, Müller R, Laage R, Kastner S, Suess S, Spoelgen R, Henriques A, Ehrenreich H, Schäbitz WR, Bach A, Schneider A | title = Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis | journal = Brain | volume = 131 | issue = Pt 12 | pages = 3335–3347 | date = December 2008 | pmid = 18835867 | pmc = 2639207 | doi = 10.1093/brain/awn243 }}</ref> These properties are currently under investigations for the development of treatments of neurological diseases such as [[cerebral ischemia]].<ref>{{cite journal | vauthors = England TJ, Sprigg N, Alasheev AM, Belkin AA, Kumar A, Prasad K, Bath PM | title = Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 36567 | date = November 2016 | pmid = 27845349 | pmc = 5109224 | doi = 10.1038/srep36567 | bibcode = 2016NatSR...636567E }}</ref>

==Genetics==
The gene for G-CSF is located on [[chromosome 17]], locus q11.2-q12. Nagata et al. found that the GCSF gene has four [[intron]]s, and that two different [[polypeptide]]s are synthesized from the same gene by differential splicing of mRNA.<ref name="pmid3484805">{{cite journal |vauthors=Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H |year=1986 |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue=6052 |pages=415–418 |bibcode=1986Natur.319..415N |doi=10.1038/319415a0 |pmid=3484805 |s2cid=4325026}}</ref>
<!-- <ref name="N86">{{cite journal  |vauthors=Nagata S, Tsuchiya M, Asano S, etal |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue=6052 |pages=415–8 |year=1986 |pmid=3484805 |doi=10.1038/319415a0}}</ref> -->

The two polypeptides differ by the presence or absence of three amino acids. Expression studies indicate that both have authentic GCSF activity.{{citation needed|date=February 2024}}

It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the [[G-CSF factor stem-loop destabilising element]].{{citation needed|date=February 2024}}

== Medical use ==
===Chemotherapy-induced neutropenia===

Chemotherapy can cause [[myelosuppression]] and unacceptably low levels of [[white blood cell]]s ([[leukopenia]]), making patients susceptible to [[infection]]s and [[sepsis]]. G-CSF stimulates the production of [[granulocyte]]s, a type of white blood cell. In [[oncology]] and [[hematology]], a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality from [[neutropenia]] after [[chemotherapy]], allowing higher-intensity treatment regimens.<ref name="pmid23788754">{{cite journal | vauthors = Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, Huang M, Crawford J | title = The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials | journal = Annals of Oncology | volume = 24 | issue = 10 | pages = 2475–2484 | date = October 2013 | pmid = 23788754 | pmc = 3841419 | doi = 10.1093/annonc/mdt226 }}</ref> It is administered to oncology patients via subcutaneous or intravenous routes.<ref>{{cite web |url= http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/cancer-drugs/gcsf|title= Granulocyte colony stimulating factor (G-CSF)|website= Cancer Research UK |access-date= 12 November 2014}}</ref> A QSP model of neutrophil production and a PK/PD model of a cytotoxic chemotherapeutic drug (Zalypsis) have been developed to optimize the use of G-CSF in chemotherapy regimens with the aim to prevent mild-neutropenia.<ref>{{cite journal | vauthors = Craig M, Humphries AR, Nekka F, Bélair J, Li J, Mackey MC | title = Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia | journal = Journal of Theoretical Biology | volume = 385 | pages = 77–89 | date = November 2015 | pmid = 26343861 | doi = 10.1016/j.jtbi.2015.08.015 | bibcode = 2015JThBi.385...77C }}</ref>

G-CSF was first trialled as a therapy for neutropenia induced by chemotherapy in 1988. The treatment was well tolerated and a dose-dependent rise in circulating neutrophils was noted.<ref>{{cite journal | vauthors = Morstyn G, Campbell L, Souza LM, Alton NK, Keech J, Green M, Sheridan W, Metcalf D, Fox R | title = Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy | journal = Lancet | volume = 1 | issue = 8587 | pages = 667–672 | date = March 1988 | pmid = 2895212 | doi = 10.1016/S0140-6736(88)91475-4 | s2cid = 21255495 }}</ref>

A study in mice has shown that G-CSF may decrease [[bone mineral density]].<ref name="pmid17192391">{{cite journal | vauthors = Hirbe AC, Uluçkan O, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, Trinkaus K, Apicelli A, Weilbaecher K | title = Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner | journal = Blood | volume = 109 | issue = 8 | pages = 3424–3431 | date = April 2007 | pmid = 17192391 | pmc = 1852257 | doi = 10.1182/blood-2006-09-048686 }}</ref>

G-CSF administration has been shown to attenuate the [[telomere]] loss associated with chemotherapy.<ref name="pmid12542495">{{cite journal | vauthors = Szyper-Kravitz M, Uziel O, Shapiro H, Radnay J, Katz T, Rowe JM, Lishner M, Lahav M | title = Granulocyte colony-stimulating factor administration upregulates telomerase activity in CD34+ haematopoietic cells and may prevent telomere attrition after chemotherapy | journal = British Journal of Haematology | volume = 120 | issue = 2 | pages = 329–336 | date = January 2003 | pmid = 12542495 | doi = 10.1046/j.1365-2141.2003.04043.x | s2cid = 5785335 | doi-access =  }}</ref>

===Use in drug-induced neutropenia===
[[Neutropenia]] can be a severe side effect of [[clozapine]], an [[antipsychotic]] medication in the treatment of [[schizophrenia]]. G-CSF can restore neutrophil count. Following a return to baseline after stopping the drug, it may sometimes be safely [[challenge-dechallenge-rechallenge|rechallenged]] with the added use of G-CSF.<ref name="Myles">{{cite journal | vauthors = Myles N, Myles H, Clark SR, Bird R, Siskind D | title = Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations | journal = The Australian and New Zealand Journal of Psychiatry | volume = 51 | issue = 10 | pages = 980–989 | date = October 2017 | pmid = 28747065 | doi = 10.1177/0004867417720516 | doi-access = free }}</ref><ref name="Lally">{{cite journal | vauthors = Lally J, Malik S, Krivoy A, Whiskey E, Taylor DM, Gaughran FP, Flanagan RJ, Mijovic A, MacCabe JH | title = The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review | journal = Journal of Clinical Psychopharmacology | volume = 37 | issue = 5 | pages = 600–604 | date = October 2017 | pmid = 28817489 | doi = 10.1097/JCP.0000000000000767 | s2cid = 41269943 | url = https://kclpure.kcl.ac.uk/portal/en/publications/ca7cfadf-aa22-4c06-ae6d-a8fcce079c12 }}</ref>

===Before blood donation===
G-CSF is also used to increase the number of [[hematopoietic stem cells]] in the blood of the donor before collection by [[leukapheresis]] for use in [[hematopoietic stem cell transplantation]]. For this purpose, G-CSF appears to be safe in [[pregnancy]] during [[implantation (human embryo)|implantation]] as well as during the [[second trimester|second and third trimesters]].<ref name=Pessach2013>{{cite journal | vauthors = Pessach I, Shimoni A, Nagler A | title = Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know? | journal = Human Reproduction Update | volume = 19 | issue = 3 | pages = 259–267 | year = 2013 | pmid = 23287427 | doi = 10.1093/humupd/dms053 | doi-access = free }}</ref> [[Breastfeeding]] should be withheld for three days after CSF administration to allow for [[clearance (medicine)|clearance]] of it from the milk.<ref name=Pessach2013/> People who have been administered colony-stimulating factors do not have a higher risk of [[leukemia]] than people who have not.<ref name=Pessach2013/>

===Stem cell transplants===
G-CSF may also be given to the receiver in [[hematopoietic stem cell transplantation]], to compensate for [[conditioning regimens]].<ref name="pmid12542495" />

==Side effect==
The skin disease [[Sweet's syndrome]] is a known side effect of using this drug.<ref name="pmid7504506">{{cite journal | vauthors = Paydaş S, Sahin B, Seyrek E, Soylu M, Gonlusen G, Acar A, Tuncer I | title = Sweet's syndrome associated with G-CSF | journal = British Journal of Haematology | volume = 85 | issue = 1 | pages = 191–192 | date = September 1993 | pmid = 7504506 | doi = 10.1111/j.1365-2141.1993.tb08668.x | s2cid = 414133 }}</ref>

== History ==
Two research teams independently identified mouse colony stimulating factors in the 1960s: Ray Bradley at [[University of Melbourne]] and [[Donald Metcalf]] at [[Walter and Eliza Hall Institute]], from [[Australia]], and Yasuo Ichikawa, Dov Pluznik and [[Leo Sachs]] at the [[Weizmann Institute of Science]], [[Israel]].<ref>{{cite journal | vauthors = Bradley TR, Metcalf D | title = The growth of mouse bone marrow cells in vitro | journal = The Australian Journal of Experimental Biology and Medical Science | volume = 44 | issue = 3 | pages = 287–299 | date = June 1966 | pmid = 4164182 | doi = 10.1038/icb.1966.28 }}</ref><ref>{{cite journal | vauthors = Ichikawa Y, Pluznik DH, Sachs L | title = In vitro control of the development of macrophage and granulocyte colonies | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 56 | issue = 2 | pages = 488–495 | date = August 1966 | pmid = 5229970 | pmc = 224399 | doi = 10.1073/pnas.56.2.488 | doi-access = free | bibcode = 1966PNAS...56..488I }}</ref><ref name=":0" /> In 1980 Antony Burgess and Donald Metcalf discovered that mouse lung conditioned medium contained at least two different CSFs <ref> {{cite journal | vauthors = Burgess AW, Metcalf D | title = Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells |journal = International Journal of Cancer | volume = 26 | issue = 5 | pages = 647-654 | date = November 1980 | doi = 10.1002/ijc.2910260517 }} </ref> - GM-CSF, which they had purified in 1977 and a G-CSF which stimulated the production of 
colonies of neutrophils. 

In 1983, Donald Metcalf's research team, led by [[Nicos Nicola]], isolated the murine cytokine from medium conditioned with lung tissue obtained from endotoxin-treated mice.<ref>{{cite journal | vauthors = Nicola NA, Metcalf D, Matsumoto M, Johnson GR | title = Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor | journal = The Journal of Biological Chemistry | volume = 258 | issue = 14 | pages = 9017–9023 | date = July 1983 | pmid = 6190815 | doi = 10.1016/S0021-9258(18)32158-6 | doi-access = free }}</ref><ref name="pmid2990035">{{cite journal | vauthors = Metcalf D | title = The granulocyte-macrophage colony-stimulating factors | journal = Science | volume = 229 | issue = 4708 | pages = 16–22 | date = July 1985 | pmid = 2990035 | doi = 10.1126/science.2990035 | s2cid = 45170361 | bibcode = 1985Sci...229...16M }}</ref><ref name=":0" />

In 1985, [[Karl Welte]], [[Erich Platzer]], [[Janice Gabrilove]], [[Roland Mertelsmann]] and [[Malcolm A. S. Moore|Malcolm Moore]] at the [[Memorial Sloan Kettering Cancer Center]] (MSK) purified human G-CSF produced by bladder cancer cell line 5637 from conditioned medium.<ref>{{cite journal | vauthors = Welte K, Platzer E, Lu L, Gabrilove JL, Levi E, Mertelsmann R, Moore MA | title = Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 5 | pages = 1526–1530 | date = March 1985 | pmid = 3871951 | pmc = 397296 | doi = 10.1073/pnas.82.5.1526 | doi-access = free | bibcode = 1985PNAS...82.1526W }}</ref><ref name=":0" />

In 1986, Karl Welte's team at MSK patented the method of producing and using human G-CSF under the name "human hematopoietic pluripotent colony stimulating factor" or "human pluripotent colony stimulating factor" (P-CSF).<ref>{{Cite web |title=Human pluripotent hematopoietic colony stimulating factor, method of production and use |url=https://patents.google.com/patent/CA1340266C/en |access-date=2025-01-10 |website=Google Patents |publication-date=1986-03-27}}</ref> Also in 1986, two independent research groups working with pharmaceutical companies cloned the G-CSF gene that made possible large-scale production and its clinical use: [[Shigekazu Nagata]]'s team in collaboration with [[Chugai Pharmaceutical Co.|Chugai Pharmaceutical Co]]. from [[Japan]], and [[Lawrence Souza]]'s team at [[Amgen]] in collaboration with Karl Welte's research team members from [[Germany]] and the [[United States|USA]].<ref name="pmid3484805" /><ref name="pmid2420009">{{cite journal |vauthors=Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK, Barendt J, Platzer E, Moore MA, Mertelsmann R, Welte K |date=April 1986 |title=Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells |journal=Science |volume=232 |issue=4746 |pages=61–65 |bibcode=1986Sci...232...61S |doi=10.1126/science.2420009 |pmid=2420009}}</ref><ref name=":0" />

==Pharmaceutical variants==
The [[recombinant DNA|recombinant]] human G-CSF (rhG-CSF) synthesised in an ''[[E. coli]]'' expression system is called [[filgrastim]]. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim.{{citation needed|date=February 2024}}

The [[Food and Drug Administration|Food and Drugs Administration]] (FDA) first approved filgrastim on February 20, 1991 marketed by [[Amgen]] with the brand name [[Neupogen]].<ref name=":1">{{Cite web | work = U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER) |first= |date=1991-02-20 |title=[Filgrastim] Application number 103353/000 |url=https://www.accessdata.fda.gov/drugsatfda_docs/bla/pre96/103353Orig1s000.pdf |url-status=live |archive-url=https://web.archive.org/web/20240927071107/https://www.accessdata.fda.gov/drugsatfda_docs/bla/pre96/103353Orig1s000.pdf | archive-date = 2024-09-27 |access-date=2025-01-11 }}</ref> It was initially approved to reduce the risk of infection in patients with non-myeloid malignancies who are taking myelosuppressive anti-cancer drugs associated with [[febrile neutropenia]] with fever.<ref name=":1" />

Several bio-generic versions are now also available in markets such as Europe and Australia. Filgrastim (Neupogen) and [[Pegfilgrastim|PEG-filgrastim]] (Neulasta), or [[pegylated]] form of filgratim, are two commercially available forms of rhG-CSF. The pegylated form of filgratim form has a much longer [[half-life]], reducing the necessity of daily injections.

The FDA approved the first [[biosimilar]] of Neulasta in June 2018. It is made by [[Mylan]] and sold as Fulphila.<ref>{{cite web |author=Office of the Commissioner |date=2019-09-11 |title=Press Announcements - FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609805.htm |archive-url=https://web.archive.org/web/20180605015355/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609805.htm |url-status=dead |archive-date=June 5, 2018 |website=www.fda.gov |language=en}}</ref>

Another form of rhG-CSF called [[lenograstim]] is synthesised in [[Chinese hamster ovary cell]]s (CHO cells). As this is a mammalian cell expression system, lenograstim is indistinguishable from the 174-amino acid natural human G-CSF. No clinical or therapeutic consequences of the differences between filgrastim and lenograstim have yet been identified, but there are no formal comparative studies.

In 2015, filgrastim was included on the [[WHO Model List of Essential Medicines]], a list containing the medications considered to be most effective and safe to meet the most important needs in a [[health system]].<ref name=":2">{{cite journal | vauthors = Cornes P, Krendyukov A | title = The evolution of value with filgrastim in oncology | journal = Future Oncology | volume = 15 | issue = 13 | pages = 1525–1533 | date = May 2019 | pmid = 30835142 | doi = 10.2217/fon-2018-0762 | doi-access = free }}</ref><ref>{{Cite web |last=WHO Essential Medicine List |title=Filgrastim |url=https://list.essentialmeds.org/medicines/89 |access-date=2025-01-11 |website=eEML}}</ref>

===Research===
G-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents.<ref>{{cite journal | vauthors = Weisdorf D, Chao N, Waselenko JK, Dainiak N, Armitage JO, McNiece I, Confer D | title = Acute radiation injury: contingency planning for triage, supportive care, and transplantation | journal = Biology of Blood and Marrow Transplantation | volume = 12 | issue = 6 | pages = 672–682 | date = June 2006 | pmid = 16737941 | doi = 10.1016/j.bbmt.2006.02.006 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Weinstock DM, Case C, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, Weisdorf DJ, Confer DL | title = Radiologic and nuclear events: contingency planning for hematologists/oncologists | journal = Blood | volume = 111 | issue = 12 | pages = 5440–5445 | date = June 2008 | pmid = 18287516 | pmc = 2424146 | doi = 10.1182/blood-2008-01-134817 }}</ref>

[[Mesoblast]] planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus [[stromal cell-derived factor-1|SDF]] (stromal cell-derived factor) directly to the heart.<ref name="isbn0-7333-1248-9">{{cite book | vauthors = Finkel E | title = Stem cells: controversy on the frontiers of science | publisher = ABC Books | location = Crows Nest | year = 2005 | isbn = 978-0-7333-1248-9 }}</ref>

G-CSF has been shown to reduce [[inflammation]], reduce [[amyloid beta]] burden, and reverse cognitive impairment in a mouse model of [[Alzheimer's disease]].<ref name="pmid19500657">{{cite journal | vauthors = Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, Cao C, Arendash GW | title = Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice | journal = Neuroscience | volume = 163 | issue = 1 | pages = 55–72 | date = September 2009 | pmid = 19500657 | pmc = 5966834 | doi = 10.1016/j.neuroscience.2009.05.071 }}</ref>

Due to its neuroprotective properties, G-CSF is currently under investigation for [[cerebral ischemia]] in a clinical phase IIb <ref>{{cite web|url=http://clinicaltrials.gov/ct/show/NCT00927836|title=AXIS 2: AX200 for the Treatment of Ischemic Stroke - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov}}</ref> and several clinical pilot studies are published for other neurological disease such as [[amyotrophic lateral sclerosis]]<ref name="pmid19922135">{{cite journal | vauthors = Zhang Y, Wang L, Fu Y, Song H, Zhao H, Deng M, Zhang J, Fan D | title = Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis | journal = Amyotrophic Lateral Sclerosis | volume = 10 | issue = 5–6 | pages = 430–431 | year = 2009 | pmid = 19922135 | doi = 10.3109/17482960802588059 | s2cid = 43087598 }}</ref> A combination of human G-CSF and [[cord blood]] cells has been shown to reduce impairment from chronic traumatic brain injury in rats.<ref name="pmid24621603">{{cite journal | vauthors = Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, Song S, Kaneko Y, Borlongan CV | title = Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e90953 | year = 2014 | pmid = 24621603 | pmc = 3951247 | doi = 10.1371/journal.pone.0090953 | doi-access = free | bibcode = 2014PLoSO...990953A }}</ref>

== See also ==
* [[PEGylation]]

== References ==
{{reflist|30em}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Duarte RF, Frank DA | title = The synergy between stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF): molecular basis and clinical relevance | journal = Leukemia & Lymphoma | volume = 43 | issue = 6 | pages = 1179–1187 | date = June 2002 | pmid = 12152985 | doi = 10.1080/10428190290026231 | s2cid = 45748453 }}
* {{cite journal | vauthors = Mroczko B, Szmitkowski M | title = Hematopoietic cytokines as tumor markers | journal = Clinical Chemistry and Laboratory Medicine | volume = 42 | issue = 12 | pages = 1347–1354 | year = 2005 | pmid = 15576295 | doi = 10.1515/CCLM.2004.253 | s2cid = 11414705 }}
* {{cite journal | vauthors = Sallerfors B, Olofsson T | title = Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays | journal = European Journal of Haematology | volume = 49 | issue = 4 | pages = 199–207 | date = October 1992 | pmid = 1281454 | doi = 10.1111/j.1600-0609.1992.tb00047.x | s2cid = 35573524 }}
* {{cite journal | vauthors = Zink T, Ross A, Ambrosius D, Rudolph R, Holak TA | title = Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy | journal = FEBS Letters | volume = 314 | issue = 3 | pages = 435–439 | date = December 1992 | pmid = 1281794 | doi = 10.1016/0014-5793(92)81521-M | s2cid = 28422738 | doi-access = free | bibcode = 1992FEBSL.314..435Z }}
* {{cite journal | vauthors = Kubota N, Orita T, Hattori K, Oh-eda M, Ochi N, Yamazaki T | title = Structural characterization of natural and recombinant human granulocyte colony-stimulating factors | journal = Journal of Biochemistry | volume = 107 | issue = 3 | pages = 486–492 | date = March 1990 | pmid = 1692828 | doi = 10.1093/oxfordjournals.jbchem.a123072 }}
* {{cite journal | vauthors = Nagata S, Tsuchiya M, Asano S, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Yamazaki T | title = The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor | journal = The EMBO Journal | volume = 5 | issue = 3 | pages = 575–581 | date = March 1986 | pmid = 2423327 | pmc = 1166801 | doi = 10.1002/j.1460-2075.1986.tb04249.x }}
* {{cite journal | vauthors = Simmers RN, Smith J, Shannon MF, Wong G, Lopez AF, Baker E, Sutherland GR, Vadas MA | title = Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia | journal = Human Genetics | volume = 78 | issue = 2 | pages = 134–136 | date = February 1988 | pmid = 2448221 | doi = 10.1007/BF00278182 | s2cid = 469736 | authorlink7 = Grant Robert Sutherland }}
* {{cite journal | vauthors = Tweardy DJ, Cannizzaro LA, Palumbo AP, Shane S, Huebner K, Vantuinen P, Ledbetter DH, Finan JB, Nowell PC, Rovera G | title = Molecular cloning and characterization of a cDNA for human granulocyte colony-stimulating factor (G-CSF) from a glioblastoma multiforme cell line and localization of the G-CSF gene to chromosome band 17q21 | journal = Oncogene Research | volume = 1 | issue = 3 | pages = 209–220 | date = August 1987 | pmid = 2453015 }}
* {{cite journal | vauthors = Tsuchiya M, Nomura H, Asano S, Kaziro Y, Nagata S | title = Characterization of recombinant human granulocyte-colony-stimulating factor produced in mouse cells | journal = The EMBO Journal | volume = 6 | issue = 3 | pages = 611–616 | date = March 1987 | pmid = 3034599 | pmc = 553441 | doi = 10.1002/j.1460-2075.1987.tb04798.x }}
<!-- cited inline * {{cite journal   |vauthors=Nagata S, Tsuchiya M, Asano S, etal |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue= 6052 |pages= 415–8 |year= 1986 |pmid= 3484805 |doi= 10.1038/319415a0 }} -->
* {{cite journal | vauthors = Devlin JJ, Devlin PE, Myambo K, Lilly MB, Rado TA, Warren MK | title = Expression of granulocyte colony-stimulating factor by human cell lines | journal = Journal of Leukocyte Biology | volume = 41 | issue = 4 | pages = 302–306 | date = April 1987 | pmid = 3494801 | doi = 10.1002/jlb.41.4.302 | s2cid = 26877622 }}
* {{cite journal | vauthors = Kanda N, Fukushige S, Murotsu T, Yoshida MC, Tsuchiya M, Asano S, Kaziro Y, Nagata S | title = Human gene coding for granulocyte-colony stimulating factor is assigned to the q21-q22 region of chromosome 17 | journal = Somatic Cell and Molecular Genetics | volume = 13 | issue = 6 | pages = 679–684 | date = November 1987 | pmid = 3499671 | doi = 10.1007/BF01534488 | s2cid = 10909775 }}
* {{cite journal | vauthors = Le Beau MM, Lemons RS, Carrino JJ, Pettenati MJ, Souza LM, Diaz MO, Rowley JD | title = Chromosomal localization of the human G-CSF gene to 17q11 proximal to the breakpoint of the t(15;17) in acute promyelocytic leukemia | journal = Leukemia | volume = 1 | issue = 12 | pages = 795–799 | date = December 1987 | pmid = 3501046 }}
* {{cite journal | vauthors = Zink T, Ross A, Lüers K, Cieslar C, Rudolph R, Holak TA | title = Structure and dynamics of the human granulocyte colony-stimulating factor determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein | journal = Biochemistry | volume = 33 | issue = 28 | pages = 8453–8463 | date = July 1994 | pmid = 7518249 | doi = 10.1021/bi00194a009 }}
* {{cite journal | vauthors = Corcione A, Baldi L, Zupo S, Dono M, Rinaldi GB, Roncella S, Taborelli G, Truini M, Ferrarini M, Pistoia V | title = Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells | journal = Journal of Immunology | volume = 153 | issue = 7 | pages = 2868–2877 | date = October 1994 | pmid = 7522243 | doi = 10.4049/jimmunol.153.7.2868 | s2cid = 25302361 | doi-access = free }}
* {{cite journal | vauthors = Watari K, Ozawa K, Tajika K, Tojo A, Tani K, Kamachi S, Harigaya K, Takahashi T, Sekiguchi S, Nagata S | title = Production of human granulocyte colony stimulating factor by various kinds of stromal cells in vitro detected by enzyme immunoassay and in situ hybridization | journal = Stem Cells | volume = 12 | issue = 4 | pages = 416–423 | date = July 1994 | pmid = 7524894 | doi = 10.1002/stem.5530120409 | s2cid = 22671177 }}
* {{cite journal | vauthors = Hill CP, Osslund TD, Eisenberg D | title = The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 11 | pages = 5167–5171 | date = June 1993 | pmid = 7685117 | pmc = 46676 | doi = 10.1073/pnas.90.11.5167 | doi-access = free | bibcode = 1993PNAS...90.5167H }}
* {{cite journal | vauthors = Haniu M, Horan T, Arakawa T, Le J, Katta V, Rohde MF | title = Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region | journal = Archives of Biochemistry and Biophysics | volume = 324 | issue = 2 | pages = 344–356 | date = December 1995 | pmid = 8554326 | doi = 10.1006/abbi.1995.0047 }}
* {{cite journal | vauthors = McCracken S, Layton JE, Shorter SC, Starkey PM, Barlow DH, Mardon HJ | title = Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta | journal = The Journal of Endocrinology | volume = 149 | issue = 2 | pages = 249–258 | date = May 1996 | pmid = 8708536 | doi = 10.1677/joe.0.1490249 }}
{{refend}}

== External links ==
* {{MeshName|Granulocyte+Colony-Stimulating+Factor}}
* {{PDBe-KB2|P09919|Granulocyte colony-stimulating factor}}

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