thumb|Cells engineered to fluoresce under UV light. '''Cell engineering''' is the purposeful process of adding, deleting, or modifying genetic sequences in living cells to achieve biological engineering goals such as altering cell production, changing cell growth and proliferation requirements, adding or removing cell functions, and many more. Cell engineering often makes use of recombinant DNA technology to achieve these modifications as well as closely related tissue engineering methods.<ref name=":02">{{Cite journal|last1=Cameron|first1=Douglas C.|last2=Tong|first2=I-Teh|date=1993-01-01|title=Cellular and metabolic engineering|url=https://doi.org/10.1007/BF02916416|journal=Applied Biochemistry and Biotechnology|language=en|volume=38|issue=1|pages=105–140|doi=10.1007/BF02916416|pmid=8346901 |issn=1559-0291|url-access=subscription}}</ref> Cell engineering can be characterized as an intermediary level in the increasingly specific disciplines of biological engineering which includes organ engineering, tissue engineering, protein engineering, and genetic engineering.<ref>{{Cite journal|last=Nerem|first=Robert M.|date=1991-09-01|title=Cellular engineering|url=https://doi.org/10.1007/BF02367396|journal=Annals of Biomedical Engineering|language=en|volume=19|issue=5|pages=529–545|doi=10.1007/BF02367396|pmid=1741530 |issn=1573-9686|url-access=subscription}}</ref>
The field of cellular engineering is gaining more traction as biomedical research advances in tissue engineering and becomes more specific. Publications in the field have gone from several thousand in the early 2000s to nearly 40,000 in 2020.<ref>{{Cite web|title=cell engineering - Search Results - PubMed|url=https://pubmed.ncbi.nlm.nih.gov/?term=cell+engineering|access-date=2021-11-19|website=PubMed|language=en}}</ref>
== Overview ==
=== Improving production of natural cellular products === One general form of cell engineering involves altering natural cell production to achieve a more desirable yield or shorter production time.<ref name=":03">{{Cite journal|last1=Cameron|first1=Douglas C.|last2=Tong|first2=I-Teh|date=1993-01-01|title=Cellular and metabolic engineering|url=https://doi.org/10.1007/BF02916416|journal=Applied Biochemistry and Biotechnology|language=en|volume=38|issue=1|pages=105–140|doi=10.1007/BF02916416|pmid=8346901|s2cid=28117582|issn=1559-0291|url-access=subscription}}</ref> A possible method for changing natural cell production includes boosting or repressing genes that are involved in the metabolism of the product. For example, researchers were able to overexpress transporter genes in hamster ovary cells to increase monoclonal antibody yield.<ref>{{Cite journal|last1=Tabuchi|first1=Hisahiro|last2=Sugiyama|first2=Tomoya|last3=Tanaka|first3=Saeko|last4=Tainaka|first4=Satoshi|date=2010|title=Overexpression of taurine transporter in Chinese hamster ovary cells can enhance cell viability and product yield, while promoting glutamine consumption|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.22880|journal=Biotechnology and Bioengineering|language=en|volume=107|issue=6|pages=998–1003|doi=10.1002/bit.22880|pmid=20661907|bibcode=2010BiotB.107..998T |s2cid=9824980|issn=1097-0290|url-access=subscription}}</ref> Another approach could involve incorporating biologically foreign genes into an existing cell line. For example, ''E.Coli'', which synthesizes ethanol, can be modified using genes from ''Zymomonas mobilis'' to make ethanol fermentation the primary cell fermentation product.<ref>{{Cite journal|last1=Ingram|first1=L O|last2=Conway|first2=T|last3=Clark|first3=D P|last4=Sewell|first4=G W|last5=Preston|first5=J F|date=1987-10-01|title=Genetic engineering of ethanol production in Escherichia coli|journal=Applied and Environmental Microbiology|volume=53|issue=10|pages=2420–2425|doi=10.1128/aem.53.10.2420-2425.1987|pmid=3322191|pmc=204123|bibcode=1987ApEnM..53.2420I}}</ref>
=== Altering cell requirements === Another beneficial cell modification is the adjustment of substrate and growth requirements of a cell. By changing cell needs, the raw material cost, equipment expenses, and skill required to grow and maintain cell cultures can be significantly reduced. For example, scientists have used foreign enzymes to engineer a common industrial yeast strain which allows the cells to grow on substrate cheaper than the traditional glucose.<ref>{{Cite journal|last1=Ledesma-Amaro|first1=Rodrigo|last2=Nicaud|first2=Jean-Marc|date=October 2016|title=Metabolic Engineering for Expanding the Substrate Range of Yarrowia lipolytica|url=https://doi.org/10.1016/j.tibtech.2016.04.010|journal=Trends in Biotechnology|volume=34|issue=10|pages=798–809|doi=10.1016/j.tibtech.2016.04.010|pmid=27207225|issn=0167-7799|url-access=subscription}}</ref> Because of the biological engineering focus on improving scale-up costs, research in this area is largely focused on the ability of various enzymes to metabolize low-cost substrates.<ref>{{Cite journal|last1=Prieto|first1=M A|last2=Perez-Aranda|first2=A|last3=Garcia|first3=J L|date=1993-04-01|title=Characterization of an Escherichia coli aromatic hydroxylase with a broad substrate range|journal=Journal of Bacteriology|volume=175|issue=7|pages=2162–2167|doi=10.1128/jb.175.7.2162-2167.1993|pmc=204336|pmid=8458860}}</ref>
=== Augmenting cells to produce new products === Closely tied with the field of biotechnology, this subject of cell engineering employs recombinant DNA methods to induce cells to construct a desired product such as a protein, antibody, or enzyme. One of the most notable examples of this subset of cellular engineering is the transformation of ''E. Coli'' to transcript and translate a precursor to insulin which drastically reduced the cost of production.<ref>{{Cite journal|last1=Goeddel|first1=D. V.|last2=Kleid|first2=D. G.|last3=Bolivar|first3=F.|last4=Heyneker|first4=H. L.|last5=Yansura|first5=D. G.|last6=Crea|first6=R.|last7=Hirose|first7=T.|last8=Kraszewski|first8=A.|last9=Itakura|first9=K.|last10=Riggs|first10=A. D.|date=1979-01-01|title=Expression in Escherichia coli of chemically synthesized genes for human insulin|journal=Proceedings of the National Academy of Sciences|language=en|volume=76|issue=1|pages=106–110|doi=10.1073/pnas.76.1.106|issn=0027-8424|pmc=382885|pmid=85300|bibcode=1979PNAS...76..106G|doi-access=free}}</ref> Similar research was conducted shortly after in 1979 in which ''E. Coli'' was transformed to express human growth hormone for use in treatment of pituitary dwarfism.<ref>{{Cite journal|last1=Goeddel|first1=David V.|last2=Heyneker|first2=Herbert L.|last3=Hozumi|first3=Toyohara|last4=Arentzen|first4=Rene|last5=Itakura|first5=Keiichi|last6=Yansura|first6=Daniel G.|last7=Ross|first7=Michael J.|last8=Miozzari|first8=Giuseppe|last9=Crea|first9=Roberto|last10=Seeburg|first10=Peter H.|date=October 1979|title=Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone|url=https://www.nature.com/articles/281544a0|journal=Nature|language=en|volume=281|issue=5732|pages=544–548|doi=10.1038/281544a0|pmid=386136|bibcode=1979Natur.281..544G|s2cid=4237998|issn=1476-4687|url-access=subscription}}</ref> Finally, much progress has been made in engineering cells to produce antigens for the purpose of creating vaccines.<ref>{{Cite journal|last1=Nascimento|first1=I. P.|last2=Leite|first2=L. C. C.|date=December 2012|title=Recombinant vaccines and the development of new vaccine strategies|journal=Brazilian Journal of Medical and Biological Research|language=en|volume=45|issue=12|pages=1102–1111|doi=10.1590/S0100-879X2012007500142|issn=0100-879X|pmc=3854212|pmid=22948379}}</ref>
=== Adjustment of cell properties === Within the focus of bioengineering, various cell modification methods are utilized to alter inherent properties of cells such as growth density, growth rate, growth yield, temperature resistance, freezing tolerance, chemical sensitivity, and vulnerability to pathogens.<ref name=":03"/> For example, in 1988 one group of researchers from the Illinois Institute of Technology successfully expressed a ''Vitreoscilla'' hemoglobin gene in ''E. Coli'' to create a strain that was more tolerant to low-oxygen conditions such as those found in high density industrial bioreactors.<ref>{{Cite journal|last1=Dikshit|first1=Kanak L.|last2=Webster|first2=Dale A.|date=1988-10-30|title=Cloning, characterization and expression of the bacterial globin gene from Vitreoscilla in Escherichia coli|url=https://dx.doi.org/10.1016/0378-1119%2888%2990209-0|journal=Gene|language=en|volume=70|issue=2|pages=377–386|doi=10.1016/0378-1119(88)90209-0|pmid=2850971|issn=0378-1119|url-access=subscription}}</ref>
=== Stem cell engineering === One distinct section of cell engineering involves the alteration and tuning of stem cells. Much of the recent research on stem cell therapies and treatments falls under the aforementioned cell engineering methods. Stem cells are unique in that they may differentiate into various other types of cells which may then be altered to produce novel therapeutics or provide a foundation for further cell engineering efforts.<ref>{{Cite journal|last1=Li|first1=Shengwen Calvin|last2=Wang|first2=Lang|last3=Jiang|first3=Hong|last4=Acevedo|first4=Julyana|last5=Chang|first5=Anthony Christopher|last6=Loudon|first6=William Gunter|date=2009-03-01|title=Stem cell engineering for treatment of heart diseases: Potentials and challenges|journal=Cell Biology International|language=en|volume=33|issue=3|pages=255–267|doi=10.1016/j.cellbi.2008.11.009|pmid=19084605|s2cid=20486657|issn=1065-6995|doi-access=free}}</ref> One example of directed stem cell engineering includes partially differentiating stem cells into myocytes to enable production of pro-myogenic factors for the treatment of sarcopenia or muscle disuse atrophy.<ref>{{Cite journal|last1=Fix|first1=Dennis K.|last2=Mahmassani|first2=Ziad S.|last3=Petrocelli|first3=Jonathan J.|last4=de Hart|first4=Naomi M.M.P.|last5=Ferrara|first5=Patrick J.|last6=Painter|first6=Jessie S.|last7=Nistor|first7=Gabriel|last8=Lane|first8=Thomas E.|last9=Keirstead|first9=Hans S.|last10=Drummond|first10=Micah J.|date=2021-12-01|title=Reversal of deficits in aged skeletal muscle during disuse and recovery in response to treatment with a secrotome product derived from partially differentiated human pluripotent stem cells|url=https://doi.org/10.1007/s11357-021-00423-0|journal=GeroScience|language=en|volume=43|issue=6|pages=2635–2652|doi=10.1007/s11357-021-00423-0|pmid=34427856|pmc=8602548|issn=2509-2723}}</ref>
== History == The phrase "cell engineering" was first used in a published paper in 1968 to describe the process of improving fuel cells.<ref>{{Cite journal|last=Thurber|first=W. C.|date=1968-05-01|title=Closure to "Discussions of 'A Fuel Cell Power Plant for a Deep Diving Submarine'" (1968, ASME J. Eng. Ind., 90, pp. 266–267)|journal=Journal of Engineering for Industry|volume=90|issue=2|pages=267|doi=10.1115/1.3604626|issn=0022-0817|doi-access=free}}</ref> The term was then adopted by other papers until the more specific "fuel-cell engineering" was used.
The first use of the term in a biological context was in 1971 in a paper which describes methods to graft reproductive caps between algae cells.<ref>{{Cite journal|last1=Bonotto|first1=S.|last2=Kirchmann|first2=R.|last3=Manil|first3=P.|date=1971-01-01|title=Cell Engineering in Acetabularia: A Graft Method for Obtaining Large Cells with Two or More Reproductive Caps|url=https://doi.org/10.1080/11263507109431460|journal=Giornale Botanico Italiano|volume=105|issue=1|pages=1–9|doi=10.1080/11263507109431460|issn=0017-0070|url-access=subscription}}</ref> Despite the rising popularity of the phrase, there remains unclear boundaries between cell engineering and other forms of biological engineering.<ref name=":03"/>
== Examples ==
* Therapeutic T cell engineering:<ref>{{Cite journal|last1=Sadelain|first1=Michel|last2=Rivière|first2=Isabelle|last3=Riddell|first3=Stanley|date=May 2017|title=Therapeutic T cell engineering|journal=Nature|language=en|volume=545|issue=7655|pages=423–431|doi=10.1038/nature22395|issn=1476-4687|pmc=5632949|pmid=28541315|bibcode=2017Natur.545..423S}}</ref> altering T cells to target cancer-related antigens for treatment * Monoclonal antibody production:<ref>{{Cite journal|last1=Rita Costa|first1=A.|last2=Elisa Rodrigues|first2=M.|last3=Henriques|first3=Mariana|last4=Azeredo|first4=Joana|last5=Oliveira|first5=Rosário|date=2010-02-01|title=Guidelines to cell engineering for monoclonal antibody production|url=https://www.sciencedirect.com/science/article/pii/S0939641109003166|journal=European Journal of Pharmaceutics and Biopharmaceutics|language=en|volume=74|issue=2|pages=127–138|doi=10.1016/j.ejpb.2009.10.002|pmid=19853660|hdl=1822/11473|issn=0939-6411|hdl-access=free}}</ref> improving monoclonal antibody production using engineered cells * ''In vivo'' cell factories:<ref>{{Cite journal|last1=Mansouri|first1=Maysam|last2=Fussenegger|first2=Martin|date=2021-09-29|title=Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells|journal=Protein & Cell|volume=13 |issue=7 |pages=476–489 |language=en|doi=10.1007/s13238-021-00876-1|pmid=34586617|pmc=9226217 |s2cid=238217661|issn=1674-8018|doi-access=free}}</ref> engineering cells to produce therapeutics within the patient's body * Directed stem cell differentiation:<ref>{{Cite journal|last1=Clause|first1=Kelly C.|last2=Liu|first2=Li J.|last3=Tobita|first3=Kimimasa|date=April 2010|title=Directed Stem Cell Differentiation: The Role of Physical Forces|journal=Cell Communication & Adhesion|language=en|volume=17|issue=2|pages=48–54|doi=10.3109/15419061.2010.492535|issn=1541-9061|pmc=3285265|pmid=20560867}}</ref> using external factors to direct stem cell differentiation * Antibody Drug Conjugates:<ref>{{Cite journal |last=Pettinato |first=Mark C. |date=2021-10-27 |title=Introduction to Antibody-Drug Conjugates |journal=Antibodies |volume=10 |issue=4 |pages=42 |doi=10.3390/antib10040042 |doi-access=free |issn=2073-4468 |pmc=8628511 |pmid=34842621}}</ref> engineering antibody and cytotoxic drug linkages for disease treatment
==References== {{reflist}}
== External links ==
* [https://www.hopkinsmedicine.org/institute_cell_engineering/ Institute for Cell Engineering] at Johns Hopkins University School of Medicine * [https://bioeng.berkeley.edu/research/cell-tissue Cell & Tissue Engineering] at University of California, Berkeley Bioengineering Department
Category:Cells Category:Cell lines Category:Molecular biology