Editing Tissue engineering (section)

== Cells as building blocks ==
[[File:Epithelial-cells.jpg|thumb|Stained cells in culture]]
Cells are one of the main components for the success of tissue engineering approaches. Tissue engineering uses cells as strategies for creation/replacement of new tissue. Examples include [[fibroblast]]s used for skin repair or renewal,<ref name="auto1">{{cite journal | vauthors = Vig K, Chaudhari A, Tripathi S, Dixit S, Sahu R, Pillai S, Dennis VA, Singh SR | display-authors = 6 | title = Advances in Skin Regeneration Using Tissue Engineering | journal = International Journal of Molecular Sciences | volume = 18 | issue = 4 | pages = 789 | date = April 2017 | pmid = 28387714 | pmc = 5412373 | doi = 10.3390/ijms18040789 | doi-access = free }}</ref> chondrocytes used for cartilage repair (MACI–FDA approved product), and hepatocytes used in liver support systems

Cells can be used alone or with support matrices for tissue engineering applications. An adequate environment for promoting cell growth, differentiation, and integration with the existing tissue is a critical factor for cell-based building blocks.<ref>{{cite journal | vauthors = Heath CA | title = Cells for tissue engineering | journal = Trends in Biotechnology | volume = 18 | issue = 1 | pages = 17–19 | date = January 2000 | pmid = 10631775 | doi = 10.1016/S0167-7799(99)01396-7 }}</ref> Manipulation of any of these cell processes create alternative avenues for the development of new tissue (e.g., cell reprogramming - somatic cells, vascularization).{{cn|date=April 2025}}

=== Isolation ===

Techniques for cell isolation depend on the cell source. Centrifugation and apheresis are techniques used for extracting cells from biofluids (e.g., blood). Whereas digestion processes, typically using enzymes to remove the extracellular matrix (ECM), are required prior to centrifugation or apheresis techniques to extract cells from tissues/organs. Trypsin and collagenase are the most common enzymes used for tissue digestion. While trypsin is temperature dependent, collagenase is less sensitive to changes in temperature.{{cn|date=April 2025}}

=== Cell sources ===
[[File:Mouse embryonic stem cells.jpg|thumb|[[Mus musculus|Mouse]] [[Mammalian embryogenesis|embryonic]] stem cells]]

''Primary cells'' are those directly isolated from host tissue. These cells provide an ex-vivo model of cell behavior without any genetic, epigenetic, or developmental changes; making them a closer replication of in-vivo conditions than cells derived from other methods.<ref>{{cite web | vauthors = Welser, Jennifer, et al. | title = Primary Cells Versus Cell Lines | publisher= ScienCell Research Laboratories | date = November 2015 |url=https://sciencellonline.com/blog/primary-cells-versus-cell-lines/}}</ref> This constraint however, can also make studying them difficult. These are mature cells, often terminally differentiated, meaning that for many cell types proliferation is difficult or impossible. Additionally, the microenvironments these cells exist in are highly specialized, often making replication of these conditions difficult.<ref>{{cite book | vauthors = Buttery LD, Bishop AE | title = Biomaterials, Artificial Organs and Tissue Engineering| chapter = Introduction to tissue engineering | volume = 279 | issue = 5349 | pages = 193–200 | date = 2005 | doi = 10.1533/9781845690861.4.193| isbn = 9781855737372}}</ref>

''Secondary cells'' A portion of cells from a primary culture is moved to a new repository/vessel to continue being cultured. Medium from the primary culture is removed, the cells that are desired to be transferred are obtained, and then cultured in a new vessel with fresh growth medium.<ref>{{cite book | vauthors = Malik, Parth, et al. | title = Practical Approach to Mammalian Cell and Organ Culture | chapter = Mammalian Cell Culture Types and Guidelines of Their Maintenance | publisher= Springer Nature | date = January 2023 | pages = 233–259 | doi = 10.1007/978-981-19-1731-8_6-2 | isbn = 978-981-19-1730-1 |chapter-url=https://link.springer.com/referenceworkentry/10.1007/978-981-19-1731-8_6-2}}</ref>  A secondary cell culture is useful in order to ensure that cells have both the room and nutrients that they require to grow. Secondary cultures are most notably used in any scenario in which a larger quantity of cells than can be found in the primary culture is desired. Secondary cells share the constraints of primary cells (see above) but have an added risk of contamination when transferring to a new vessel.{{cn|date=April 2025}}

=== Genetic classifications of cells ===

Autologous: The donor and the recipient of the cells are the same individual. Cells are harvested, cultured or stored, and then reintroduced to the host. As a result of the host's own cells being reintroduced, an antigenic response is not elicited. The body's immune system recognizes these re-implanted cells as its own, and does not target them for attack. Autologous cell dependence on host cell health and donor site morbidity may be deterrents to their use. Adipose-derived and bone marrow-derived mesenchymal stem cells are commonly autologous in nature, and can be used in a myriad of ways, from helping repair skeletal tissue to replenishing beta cells in diabetic patients.<ref>{{cite journal | vauthors = Parekkadan B, Milwid JM | title = Mesenchymal stem cells as therapeutics | journal = Annual Review of Biomedical Engineering | volume = 12 | pages = 87–117 | date = August 2010 | pmid = 20415588 | doi = 10.1146/annurev-bioeng-070909-105309 | pmc = 3759519 }}</ref><ref>{{cite journal | vauthors = Domínguez-Bendala J, Lanzoni G, Inverardi L, Ricordi C | title = Concise review: mesenchymal stem cells for diabetes | journal = Stem Cells Translational Medicine | volume = 1 | issue = 1 | pages = 59–63 | date = January 2012 | pmid = 23197641 | doi = 10.5966/sctm.2011-0017 | pmc = 3727686 }}</ref><ref>{{cite journal | vauthors = Bara JJ, Richards RG, Alini M, Stoddart MJ | title = Concise review: Bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic | journal = Stem Cells | volume = 32 | issue = 7 | pages = 1713–23 | date = July 2014 | pmid = 24449458 | doi = 10.1002/stem.1649 | s2cid = 30744973 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Minteer D, Marra KG, Rubin JP | title = Adipose-derived mesenchymal stem cells: biology and potential applications | journal = Advances in Biochemical Engineering/Biotechnology | volume = 129 | pages = 59–71 | date = 2013 | pmid = 22825719 | doi = 10.1007/10_2012_146 | isbn = 978-3-642-35670-4 }}</ref>

Allogenic: Cells are obtained from the body of a donor of the same species as the recipient. While there are some ethical constraints to the use of human cells for in vitro studies (i.e. human brain tissue chimera development<ref>{{cite journal | vauthors = Farahany NA, Greely HT, Hyman S, Koch C, Grady C, Pașca SP, Sestan N, Arlotta P, Bernat JL, Ting J, Lunshof JE, Iyer EP, Hyun I, Capestany BH, Church GM, Huang H, Song H | display-authors = 6 | title = The ethics of experimenting with human brain tissue | journal = Nature | volume = 556 | issue = 7702 | pages = 429–32 | date = April 2018 | pmid = 29691509 | doi = 10.1038/d41586-018-04813-x | pmc = 6010307 | bibcode = 2018Natur.556..429F }}</ref>), the employment of dermal fibroblasts from human foreskin demonstrates an immunologically safe and thus a viable choice for allogenic tissue engineering of the skin.

Xenogenic: These cells are derived isolated cells from alternate species from the recipient. A notable example of xenogeneic tissue utilization is cardiovascular implant construction via animal cells. Chimeric human-animal farming raises ethical concerns around the potential for improved consciousness from implanting human organs in animals.<ref>{{cite journal | vauthors = Bourret R, Martinez E, Vialla F, Giquel C, Thonnat-Marin A, De Vos J | title = Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs | journal = Stem Cell Research & Therapy | volume = 7 | issue = 1 | pages = 87 | date = June 2016 | pmid = 27356872 | doi = 10.1186/s13287-016-0345-9 | pmc = 4928294 | doi-access = free }}</ref>

Syngeneic or isogenic: These cells describe those borne from identical genetic code. This imparts an immunologic benefit similar to autologous cell lines (see above).<ref>{{cite book | vauthors = Murphy K | date=  2016 | title= Janeway's Immunobiology | publisher= Norton, W.W. & Company, Inc.| isbn=978-0815345053}}{{page needed|date=July 2021}}</ref> Autologous cells can be considered syngenic, but the classification also extends to non-autologously derived cells such as those from an identical twin, from genetically identical (cloned) research models, or [[Induced stem cells|induced stem cells (iSC)]]<ref>{{cite journal | vauthors = Grobarczyk B, Franco B, Hanon K, Malgrange B | title = Generation of Isogenic Human iPS Cell Line Precisely Corrected by Genome Editing Using the CRISPR/Cas9 System | journal = Stem Cell Reviews and Reports | volume = 11 | issue = 5 | pages = 774–87 | date = October 2015 | pmid = 26059412 | doi = 10.1007/s12015-015-9600-1 | s2cid = 18897400 }}</ref> as related to the donor.

=== Stem cells ===
{{Unreferenced section|date=August 2024}}
''[[Stem cell]]s'' are undifferentiated cells with the ability to divide in culture and give rise to different forms of specialized cells. Stem cells are divided into "adult" and "embryonic" stem cells according to their source. While there is still a large ethical debate related to the use of embryonic stem cells, it is thought that another alternative source – [[induced pluripotent stem cells]]{{snd}}may be useful for the repair of diseased or damaged tissues, or may be used to grow new organs.

''[[totipotency|Totipotent]]'' cells are stem cells which can divide into further stem cells or differentiate into any cell type in the body, including extra-embryonic tissue.

''[[pluripotency|Pluripotent]]'' cells are stem cells which can differentiate into any cell type in the body except extra-embryonic tissue. [[induced pluripotent stem cells]] (iPSCs) are subclass of pluripotent stem cells resembling embryonic stem cells (ESCs) that have been derived from adult differentiated cells. iPSCs are created by altering the expression of transcriptional factors in adult cells until they become like embryonic stem cells.

''[[multipotency|Multipotent]]'' stem cells can be differentiated into any cell within the same class, such as [[blood]] or [[bone]]. A common example of multipotent cells is [[Mesenchymal stem cell]]s (MSCs).