Scientists have developed the first patient-derived stem cell model of albinism. The model will help studying eye conditions related to oculocutaneous albinism (OCA).
Stem selle ongespesialiseerd is. Hulle kan nie enige spesifieke funksie in die liggaam verrig nie, maar hulle kan hulself oor 'n lang tyd verdeel en vernuwe en het potensiaal om gespesialiseerd te word en te ontwikkel tot baie verskillende tipes in die liggaam soos spierselle, bloedselle, breinselle ens.
Stem cells are present in our bodies at all stages of life, from embrio to adulthood. Embryonic stem cells (ESCs) or fetal stamselle word in die vroegste stadium gesien, terwyl volwasse stamselle wat as 'n herstelstelsel vir die liggaam dien, in volwassenheid gesien word.
Stem cells can be grouped into four: embryonic stem cells (ESCs), adult stem cells, kanker stem cells (CSCs) and induced pluripotent stem cells (iPSCs). Embryonic stem cells (ESCs) are derived from inner mass cells of the blastocyst-stage of mammalian embryo that are three to five days old. They can self-renew indefinitely and differentiate into cell types of all three germ layers. On the other hand, adult stem cells serve as a repair system to maintain cell homeostasis in tissues. They can replace dead or injured cells but have limited proliferation and differentiation potential in comparison with ESCs. Cancer stem cells (CSCs) arise from normal stem cells that undergo gene mutations. They initiate tumours forming a large colony or clones. Cancer stem cells play important roles in malignant tumours hence targeting them could provide a way to treat cancers.
Geïnduseerde pluripotente stamselle (iPSCs) is afgelei van volwasse somatiese selle. Hul pluripotensie word kunsmatig in die laboratorium geïnduseer deur somatiese selle te herprogrammeer deur gene en ander faktore. iPSC's is soos embrioniese stamselle in proliferasie en differensiasie. Die eerste iPSC is ontwikkel uit muriene fibroblaste deur Yamanaka in 2006. Sedertdien is verskeie menslike iPSC's ontwikkel uit pasiënt-spesifieke monsters. Aangesien die genetika van die pasiënt in die genetika van die iPSC's weerspieël word, word hierdie herprogrammeerde somatiese selle gebruik om genetiese siektes te modelleer en het die studie van menslike genetiese afwykings 'n rewolusie veroorsaak.
'n Model is 'n dier of selle wat alle of sommige van die patologiese prosesse vertoon wat in 'n werklike siekte waargeneem word. Beskikbaarheid van 'n eksperimentele model is belangrik om die ontwikkeling van siektes op sellulêre en molekulêre vlakke te verstaan, wat help met die ontwikkeling van terapieë om te behandel. 'n Model help om te verstaan hoe die siekte ontwikkel en om potensiële behandelingsbenaderings te toets. 'n Mens kan byvoorbeeld effektiewe geneesmiddelteikens met behulp van 'n model identifiseer of klein molekules sif wat die erns kan verminder en die vordering van die siekte kan stop. Dieremodelle word al lank gebruik, maar het verskeie nadele. Verder is diermodelle nie geskik vir genetiese afwykings nie as gevolg van genetiese ongelykhede. Nou word menslike stamselle (embrioniese en geïnduseerde pluripotente) toenemend gebruik om menslike siektes te modelleer.
Siektemodellering met menslike iPSC's is al vir verskeie suksesvol gedoen voorwaardes soos laterale sklerose, bloedafwykings, diabetes, Huntington se siekte, spinale spieratrofie, ens. menslike iPSC-modelle of human neural diseases, congenital heart diseases and other genetic versteurings.
Menslike iPSC-model van albinisme was egter eers op 11 Januarie 2022 beskikbaar toe die wetenskaplikes by die National Eye Institute (NEI) wat deel is van die National Institutes of Health (NIH) die ontwikkeling van 'n menslike iPSC-gebaseerde in vitro-model vir okulokutane albinisme (OCA)
Oculocutaneous albinism (OCA) is a genetiese afwyking affecting pigmentation in the eye, skin, and hair. The patients suffer eye problems like reduced best-corrected visual acuity, reduced ocular pigmentation, abnormalities in fovea development, and/or abnormal crossing of optic nerve fibres. It is thought that improving eye pigmentation could prevent or rescue some of the vision defects.
The researchers developed an in-vitro model for studying pigmentation defects in human retinal pigment epithelium (RPE) and showed that the retinale pigment epithelium tissue derived in vitro from patients recapitulates the pigmentation defects seen in albinism. This is very interesting in view of the fact that animal models of albinism are unsuitable and there is limited human cell lines to study melanogenesis and pigmentation defects. The patient-derived OCA1A- and OCA2-iPSCs developed in this study can be a renewable and reproducible source of cells for the production of target cell and/or tissue types. In vitro derived OCA tissues and OCA-iRPE will allow deeper understanding of how melanin formation takes place and identify molecules involved in pigmentation defects, and further probe for molecular and/or physiologic differences.
Dit is 'n baie belangrike stap vorentoe in die rigting van die doel van behandeling van okulokutane albinisme (OCA) verwante toestande.
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Verwysings:
- Avior, Y., Sagi, I. & Benvenisty, N. Pluripotente stamselle in siektemodellering en geneesmiddelontdekking. Nat Rev Mol Cell Biol 17, 170–182 (2016). https://doi.org/10.1038/nrm.2015.27
- Chamberlain S., 2016. Siektemodellering met behulp van menslike iPSC's. Menslike Molekulêre Genetika, Jaargang 25, Uitgawe R2, 1 Oktober 2016, Bladsye R173–R181, https://doi.org/10.1093/hmg/ddw209
- Bai X., 2020. Stamselgebaseerde siektemodellering en selterapie. Cells 2020, 9(10), 2193; https://doi.org/10.3390/cells9102193
- George A., et al 2022. In vitro-siektemodellering van okulokutane albinisme tipe I en II met behulp van menslike geïnduseerde pluripotente stamsel-afgeleide retinale pigmentepiteel (2022). Stamselverslae. Volume 17, Uitgawe 1, P173-186, 11 Januarie 2022 DOI: https://doi.org/10.1016/j.stemcr.2021.11.016
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