Researchers at the Wellcome Trust Sanger Institute and their collaborators have created Expanded Potential Stem Cells (EPSCs) in mice, for the first time, that have a greater potential for development than current stem cell lines. These stem cells have the features of the very first cells in the developing embryo, and can develop into any type of cell.
Published today in Nature (11th October) the methods used could also help produce similar stem cell lines from human and other mammalian species, including those such as pigs or cows where embryonic stem cell lines are still not available.
The researchers also believe that their study could have implications for human regenerative medicine and for understanding miscarriage and developmental disorders.
Stem cells have the ability to develop into other cell types, and existing stem cell lines are already extremely useful for research into development, disease and treatments. However, the two currently available types of stem cell lines -- Embryonic Stem cells (ES) and induced Pluripotent Stem cells (iPS) -- have certain limitations. It is not currently possible for them to form every type of cell since they are already excluded from developing certain cell lineages.
To discover new stem cells for use in research and regenerative medicine, the researchers created a way of culturing cells from the earliest stage of development, when the fertilised egg has only divided into 4 or 8 cells that are still considered to retain some totipotency -- the ability to produce all cell types. Their hypothesis was that these cells should be less programmed than ES cells, which are taken from the around-100-cell stage of development -- called a blastocyst. They grew these early cells in a special growth condition that inhibited key development signals and pathways.
The scientists discovered that their new cultured cells kept the desired development characteristics of the earliest cells and named them Expanded Potential Stem Cells (EPSCs). Importantly, they were also able to reprogramme mouse ES cells and iPS cells in the new condition and create EPSCs from these cells, turning back the development clock to the very earliest cell type.
Dr Pentao Liu, lead researcher of this project, from the Wellcome Trust Sanger Institute and an affiliate faculty member of the Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, said: "The earliest cell is like a blank piece of paper, in theory it should have the greatest development potential. This is the first time that stable stem cell lines of these earliest mouse cells have been possible, and we see that they do indeed keep the molecular features of the 4-8 cell embryo and can develop into any cell type."
As a fertilised egg develops into a blastocyst, it produces cells that will form the embryo -- where ES cells come from -- and two other types of cell that will develop into the placenta or the yolk sac. It is possible to establish three different types of stem cells -- including ES cells -- from these three cell types in the blastocyst. EPSCs are the first stem cells that are able to produce all three types of blastocyst stem cells, which gives them much greater potential for development.
Dr Jian Yang, a first author on the paper from the Wellcome Trust Sanger Institute, said: "EPSCs provide a platform to study early embryo cells in detail at the molecular level to understand development, not only in mouse, but ultimately in future in humans. This new method of producing stem cells could be enormously helpful for studying development, more efficiently generating functional human cells, and researching treatments for pregnancy problems such as pre-eclampsia and miscarriages."
Professor Hiro Nakauchi, a co-author on the paper from Stanford University, said: "This is a fantastic achievement, by working with the very earliest cells, this study has created stem cell lines that can form both embryonic and all the extra-embryonic cells. The methods and insights from this study in mice could be used to help establish cultures of similar stem cells from other mammalian species, including those where no ES or iPS cell lines are available yet. The research also has great implications for human regenerative medicine as stem cells with improved development potential open up new opportunities. Further research in this area is vital, so that we can properly explore the potential of these cells."
Cite This Page:
Watafiti wa Taasisi ya Wellcome Trust Sanger na washirika wao wameunda seli za msingi za uwezekano ulioongezwa (EPSCs) katika panya, kwa mara ya kwanza, ambazo zina uwezo mkubwa wa maendeleo kuliko mistari ya sasa ya seli za msingi. Chembe hizi za msingi zina sifa za chembe za kwanza kabisa katika kiinitete kinachoendelea, na zinaweza kuendeleza kuwa aina yoyote ya chembe. Utafiti huo, uliochapishwa katika jarida la Nature, ulionyesha kuwa mbinu hizo zinaweza kusaidia kutengeneza seli za asili kutoka kwa binadamu na wanyama wengine, ikiwa ni pamoja na nguruwe na ng'ombe, ambapo seli za asili za kiinitete bado hazipatikani. Watafiti pia wanaamini kwamba utafiti wao unaweza kuwa na athari kwa dawa ya kurudisha upya ya binadamu na kwa kuelewa mimba na matatizo ya ukuaji. Seli za shina zina uwezo wa kugeuka kuwa aina nyingine za seli, na mstari wa seli za shina zilizopo tayari ni muhimu sana kwa utafiti wa maendeleo, magonjwa na matibabu. Hata hivyo, aina mbili za sasa za mstari wa seli za shina - seli za shina za kiinitete (ES) na seli za shina za pluripotent (iPS) - zina mapungufu fulani. Kwa sasa haiwezekani kwa wao kuunda kila aina ya seli kwa kuwa tayari wameondolewa katika kuendeleza nasaba fulani za seli. Kwa ajili ya kugundua seli za msingi mpya kwa ajili ya matumizi katika utafiti na dawa ya kuzaliana, watafiti waliunda njia ya kukuza seli kutoka hatua ya mapema ya maendeleo, wakati yai iliyozalishwa imegawanyika katika seli nne au nane tu ambazo bado zinachukuliwa kuhifadhi totipotency - uwezo wa kuzalisha aina zote za seli. Kwa mujibu wa utafiti huo, seli hizo zina uwezo wa kuunda chembe za ES ambazo zina umri wa miaka 100 na zinaitwa blastocyst. Walipanua seli hizi za mapema katika hali maalum ya ukuaji ambayo ilizuia ishara muhimu za maendeleo na njia. "Wanasayansi waligundua kwamba chembe zao mpya zilizopandwa zilihifadhi sifa za maendeleo ya chembe za awali na kuziita "" Expanded Potential Stem Cells "" (EPSCs)." Kwa hivyo, waliweza kuunda seli za ES na iPS za panya katika hali mpya na kuunda EPS kutoka kwa seli hizi, wakirudisha saa ya maendeleo kwa aina ya seli ya mapema zaidi. "Pentacleo Liu, mtafiti mkuu wa mradi huu kutoka Taasisi ya Wellcome Trust Sanger na mwanachama wa kitivo cha Wellcome Trust-MRC Stem Cell Institute, Chuo Kikuu cha Cambridge, alisema: ""Kesi ya kwanza ya seli ni kama kipande cha karatasi tupu, kwa nadharia inapaswa kuwa na uwezo mkubwa wa maendeleo." "Hii ni mara ya kwanza kwamba mstari wa seli za msingi za seli za panya za mapema zaidi zimewezekana, na tunaona kwamba kwa kweli zinaweka sifa za molekuli za kiinitete cha seli 4-8 na zinaweza kuendeleza kuwa aina yoyote ya seli. """ Wakati yai linapoendelea kuwa blastocyst, hujumuisha chembe za kiinitete (ESCs) na chembe za pili (placenta). Kuna aina tatu za seli za msingi, pamoja na seli za ES, ambazo zinaweza kuunganishwa na seli za blastocyst. EPSCs ni seli za msingi za kwanza zinazozalisha aina zote tatu za seli za msingi za blastocyst, na hivyo kuwa na uwezo mkubwa zaidi wa kuendeleza. "Jian Yang, mwandishi wa kwanza wa jarida hilo kutoka Taasisi ya Wellcome Trust Sanger, alisema: ""EPSCs hutoa jukwaa la kusoma seli za mapema za kiinitete kwa undani katika kiwango cha molekuli kuelewa maendeleo, sio tu katika panya, lakini hatimaye katika siku zijazo kwa wanadamu." "Njia hii mpya ya kutengeneza seli za shina inaweza kuwa na manufaa makubwa kwa ajili ya kujifunza maendeleo, kutengeneza seli za binadamu kwa ufanisi zaidi, na kuchunguza matibabu ya matatizo ya ujauzito kama vile pre-eclampsia na mimba za kuharibika.""" "Hiro Nakauchi, profesa wa Chuo Kikuu cha Stanford, alisema: ""Hii ni mafanikio ya ajabu, kwa kufanya kazi na seli za mapema sana, utafiti huu umefanya mistari ya seli za msingi ambazo zinaweza kuunda seli za kiinitete na seli zote za nje ya kiinitete." Utafiti huo unaonyesha kuwa chembe za msingi za wanyama wengine zinaweza kutumiwa kuendeleza chembe za msingi za wanyama wengine, ikiwa ni pamoja na wale ambao bado hawajaweza kupata chembe za ES au iPS. Utafiti huo pia una athari kubwa kwa dawa ya kurudisha upya ya binadamu kama seli za shina na uwezo wa maendeleo ulioboreshwa hufungua fursa mpya. Utafiti zaidi katika eneo hili ni muhimu, ili tuweze kuchunguza vizuri uwezo wa chembe hizi. " Namba hii ya ukurasa: