Amaseli E-Mutant Stem Adelela Imithetho Yokuthuthukiswa

Ake ucabange ubhaka ikhekhe, kodwa uphelelwe usawoti. Ngisho nesithako esingekho, i-batter isabukeka njenge-batter yekhekhe, ngakho-ke uyinamathisele kuhhavini bese uwela iminwe yakho, ulindele ukuphetha ngokuthile eduze nekhekhe elivamile. Kunalokho, ubuya ngemva kwehora ukuze uthole isiteki esiphekwe ngokugcwele.

Kuzwakala njengehlaya elingokoqobo, kodwa lolu hlobo loguquko olushaqisayo yilokho okwenzeka ngempela esitsheni samangqamuzana esiqu segundane lapho ososayensi baseGladstone Institutes bekhipha isakhi sofuzo esisodwa—amangqamuzana esiqu ayemiselwe ukuba amangqamuzana enhliziyo avele afane nozandulela wamangqamuzana obuchopho. Ukubona ithuba lososayensi kukhulisa lokho ababecabanga ukuthi bayakwazi mayelana nokuthi ama-stem cells aphenduka abe amaseli abantu abadala futhi alondoloze ubunikazi bawo njengoba ekhula.

"Lokhu kuyinselele ngempela imiqondo eyisisekelo mayelana nokuthi amangqamuzana ahlala kanjani enkambweni lapho eqala indlela yokuba amangqamuzana enhliziyo noma obuchopho," kusho uBenoit Bruneau, PhD, umqondisi we-Gladstone Institute of Cardiovascular Disease kanye nomlobi ophezulu wocwaningo olusha olushicilelwe. Imvelo.

Akukho Ukubuyela Emuva

Ama-Embryonic stem cells ane-pluripotent—anekhono lokuhlukanisa, noma ukuguqula, abe lonke uhlobo lweseli emzimbeni womuntu omdala owakheke ngokugcwele. Kodwa kuthatha izinyathelo eziningi ukuze ama-stem cells abangele izinhlobo zamangqamuzana amadala. Endleleni yabo yokuba amaseli enhliziyo, isibonelo, amaseli e-embryonic stem aqala ukuhlukana abe i-mesoderm, enye yezicubu ezintathu zokuqala ezitholakala emibungu yokuqala. Ngokuqhubekayo phansi endleleni, amangqamuzana e-mesoderm ahluma ukuze enze amathambo, imisipha, imithambo yegazi, namangqamuzana enhliziyo ashayayo.

Kwamukeleka kahle ukuthi uma iseli seliqalile ukuhlukanisa enye yalezi zindlela, alikwazi ukujika ukuze likhethe isiphetho esihlukile.

“Kakhulu wonke usosayensi okhuluma ngokudalelwa kwamangqamuzana usebenzisa isithombe sezwe laseWaddington, elibukeka lifana ne-ski resort enemithambeka ehlukahlukene eyehlela ezigodini eziwumqansa, ezihlukene,” kusho uBruneau, ophinde abe nguSihlalo kaWilliam H. Omncane. ocwaningweni lweCardiovascular Research eGladstone kanye noprofesa wezifo zezingane e-UC San Francisco (UCSF). Uma ingqamuzana lisesigodini esijulile, ayikho indlela yokuba ligxumele liwele esigodini esihluke ngokuphelele.”

Eminyakeni eyishumi edlule, Umphenyi Omkhulu we-Gladstone u-Shinya Yamanaka, MD, PhD, uthole ukuthi ungawahlela kanjani kabusha amaseli abantu abadala ahluke ngokuphelele abe amaseli esiqu e-pluripotent. Nakuba lokhu kungazange kunikeze amaseli amandla okugxuma phakathi kwezigodi, kusebenze njengokukhuphuka kwe-ski ebuyela phezulu endaweni ehlukanisayo.

Kusukela lapho, abanye abacwaningi bathole ukuthi ngezimpawu zamakhemikhali ezifanele, amanye amangqamuzana angaguqulwa abe izinhlobo ezihlobene eduze ngenqubo ebizwa ngokuthi “i-direct reprogramming”—njengendlela enqamulelayo ehlathini phakathi kwemizila eseduze yokushushuluza. Kodwa akukho kulezi zimo lapho amaseli akwazi ukugxuma ngokuzenzakalelayo phakathi kwezindlela ezihluke kakhulu. Ikakhulukazi, amaseli e-mesoderm awakwazanga ukuba izandulela zezinhlobo ezikude njengamaseli obuchopho noma amaseli amathumbu.

Nokho, ocwaningweni olusha, uBruneau nozakwabo babonisa ukuthi, ngokumangazayo, izandulela zamangqamuzana enhliziyo zingashintsha ngempela zibe izandulela zamangqamuzana obuchopho—uma iphrotheni ebizwa ngokuthi iBrahma ingekho.

Ukubuka Okumangazayo

Abacwaningi bebetadisha iqhaza lephrotheni iBrahma ekwehlukaniseni amaseli enhliziyo, ngoba bathola ngo-2019 ukuthi lisebenza ndawonye namanye ama-molecule ahambisana nokwakheka kwenhliziyo.

Esitsheni samaseli e-embryonic stem cell, basebenzise izindlela zokuhlela ze-CRISPR ukucisha isakhi sofuzo i-Brm (lesi esikhiqiza iphrotheni i-Brahma). Futhi baqaphela ukuthi amangqamuzana ayengasahlukani nezandulela ezivamile zamangqamuzana enhliziyo.

“Ngemva kwezinsuku eziyi-10 zokuhlukaniswa, amangqamuzana avamile ashaya ngesigqi; bangamaseli enhliziyo ngokucacile,” kusho uSwetansu Hota, PhD, umbhali wokuqala wocwaningo kanye nososayensi osebenzayo eBruneau Lab. Kodwa ngaphandle kukaBrahma, kwakunenqwaba yamangqamuzana angasebenzi. Akukho nhlobo ukushaywa.”

Ngemva kokuhlaziya okwengeziwe, ithimba likaBruneau labona isizathu esenza ukuthi amangqamuzana angashayi kwakungoba ukususa i-Brahma akuzange nje kuvale izakhi zofuzo ezidingekayo kumangqamuzana enhliziyo, kodwa futhi kwasebenza izakhi zofuzo ezidingekayo kumaseli obuchopho. Amaseli ezandulela inhliziyo manje ayesengamaseli obuchopho andulelayo.

Abacwaningi babe sebelandela zonke izinyathelo zokuhlukanisa, futhi bathola ngokungalindelekile ukuthi lawa maseli awazange abuyele esimweni se-pluripotent. Esikhundleni salokho, amaseli athatha igxathu elikhulu kakhulu phakathi kwemigudu ye-stem cell kunanini ngaphambili.

“Esakubona ukuthi ingqamuzana elisesigodini esisodwa sezwe laseWaddington, elinezimo ezifanele, lingagxumela kwesinye isigodi ngaphandle kokuthatha ikheshi libuyele esiqongweni kuqala,” kusho uBruneau.

Izifundo Zezifo

Nakuba indawo yamaseli esitsheni selebhu nakuwo wonke umbungu ihluke kakhulu, okuphawulwe ngabacwaningi kunezifundo mayelana nempilo yamangqamuzana kanye nezifo. Ukuguqulwa kwezakhi zofuzo ze-Brm kuye kwahlotshaniswa nesifo senhliziyo sokuzalwa kanye nama-syndromes ahlanganisa ukusebenza kobuchopho. Isakhi sofuzo siphinde sibandakanyeke emidlavuza eminingi.

"Uma ukususa i-Brahma kungashintsha amaseli e-mesoderm (njengama-cell cell precursors) abe amangqamuzana e-ectoderm (njengamangqamuzana obuchopho) esitsheni, mhlawumbe ukuguqulwa kofuzo lwe-Brm yikho okunikeza amanye amangqamuzana omdlavuza amandla okushintsha kakhulu uhlelo lwawo lofuzo," kusho uBruneau.

Okutholakele kubalulekile futhi ezingeni eliyisisekelo lokucwaninga, uyanezela, njengoba lingacacisa ukuthi amangqamuzana angashintsha kanjani uhlamvu lwawo ezilungiselelweni zezifo, njengokuhluleka kwenhliziyo, nokuthuthukisa izindlela zokwelapha ezivuselelayo, ngokufaka amangqamuzana enhliziyo amasha isibonelo.

“Ucwaningo lwethu luphinde lusitshele ukuthi izindlela zokuhlukanisa ziyinkimbinkimbi kakhulu futhi zintekenteke kakhulu kunalokho ebesikucabanga,” kusho uBruneau. “Ulwazi olungcono lwezindlela zokuhlukanisa lungasisiza futhi ukuba siqonde inhliziyo esizalwa nayo—kanye nezinye—iziphambeko, ezivela ngokwengxenye ngenxa yokwehlukana okunesici.”