I-Thrombopoietin (TPO) iyihomoni ebalulekile ye-glycoprotein edlala indima enkulu ekulawulweni kokukhiqizwa kwamaplatelet kanye ne-homeostasis. Isebenza njengesikhuthazi esiyinhloko esilawula i-thrombopoiesis — inqubo lapho ama-megakaryocyte emnkantsha wentambo akhiqiza khona amaplatelet. Ukuqonda indlela ye-thrombopoietin kunikeza imininingwane eyisihluthulelo ekulawulweni kwamaplatelet, ukusebenzisana kwesistimu yokuzivikela komzimba, kanye nezindlela zokwelapha ezingenzeka ze-thrombocytopenia nezinye izifo ezihlobene.

Lesi sihloko sihluza izindlela eziyinkimbinkimbi ngemuva komsebenzi we-TPO, ukukhiqizwa kwamaplatelet, ukususwa, nokuguga, kanye nemiphumela yalezi zinqubo ekwelashweni komtholampilo nasezifundweni zesikhathi esizayo. Siphinde sigqamise ukuxhumana phakathi kwe-thrombopoietin nezimpendulo zomzimba, sikhombise ukubaluleka kwayo ngaphezu kwe-hematopoiesis. Ngaphezu kwalokho, indima ye-Stellar Biotech Limited njengenkampani yezempilo yomhlaba wonke egxile emikhiqizweni ye-recombinant human thrombopoietin kanye nezinikelo zayo ekwelashweni kwe-thrombopoiesis izoxoxwa kancane.

Yatholakala ngeminyaka-1990, i-thrombopoietin yabonakala njenge-hematopoietic growth factor ebalulekile edingekayo ekulawuleni ukukhiqizwa kwamaplatelet. I-TPO, eyenziwa ikakhulukazi isibindi nezinso, ibopha ku-receptor ye-c-Mpl (CD110) ekhona kumangqamuzana e-hematopoietic stem cells kanye nama-megakaryocyte progenitors, ibakhuthaza ukuthi bandele futhi bahlukanise. Lokhu kukhuthaza kuthinta ngqo ubungako nekhwalithi yamaplatelet akhululwa egazini.

Amatelet, noma i-thrombocytes, ayizicucu zamangqamuzana ezincane, ezingenayo i-nucleus, ezibalulekile ekujiyeni kwegazi nasekupholisweni kwamanxeba. Ukugcina inani elanele lamaplatelet kubalulekile ukuvimbela izifo zokopha ngenkathi kugwenywa ukwakheka kwe-clot okweqile. Indlela ye-thrombopoietin ihlinzeka ngomjikelezo wokubuyisela emuva olungisa ukukhiqizwa kwamaplatelet ngokusekelwe ezingeni lamaplatelet asemoyeni, ngaleyo ndlela kugcinwa ibhalansi ye-hemostatic.

Uma kunokuntuleka noma ukuphazamiseka kokudluliswa kwezimpawu ze-TPO, iziguli zingathola i-thrombocytopenia—isimo esibonakala ngokuba namazinga aphansi kakhulu ama-platelet—okubeka izingozi zokopha kanye nokungasebenzi kahle kwezimpawu zomzimba zokuzivikela. I-thrombopoietin eyenziweyo njenge-TPIAO ekhiqizwa yizinkampani ezifana ne-Stellar Biotech Limited inikeza izindlela zokwelapha ezithembisayo kulezi zimo.

I-Thrombopoiesis iqala ngamaseli e-hematopoietic stem emnkomeni womlomo ehlukana abe ama-megakaryocyte progenitors ngaphansi kwethonya le-thrombopoietin. Ukubopha kwe-TPO ku-receptor ye-c-Mpl kuqala ukudluliswa kwezimpawu ngaphakathi komzimba okukhuthaza ukuvuthwa kwama-megakaryocyte, amanye amakhamera amakhulu anama-polyploid akwazi ukukhiqiza ama-platelet ayizinkulungwane ngayinye.

Njengoba ama-megakaryocyte evuthwa, akhulisa izitho zeselula ezibizwa ngama-proplatelet angene emithanjeni yegazi emathanjeni, lapho ama-platelet ekhishwa khona egazini. Izinga lokukhiqizwa kwama-platelet lilawulwa kahle ngamazinga ajikelezayo e-TPO, ahambisana ngokungafani nenani lama-platelet. Lapho inani lama-platelet liwela phansi, i-TPO yamahhala ethe xaxa iyatholakala ukuze ivuselele ama-megakaryocyte, yandise ukuphuma kwama-platelet.

I-Stellar Biotech Limited igxile ekuthuthukisweni nasekuthengisweni kwemikhiqizo ye-recombinant human thrombopoietin (rhTPO) esebenzisa le ndlela yemvelo ukwelapha i-thrombocytopenia. Umkhiqizo wabo, i-TPIAO, uklanyelwe ukulingisa umsebenzi we-endogenous TPO futhi usekele ukubuyiselwa kwamaplatelet ezigulini ezinamanani aphansi amaplatelet abangelwa izimo ezahlukahlukene zezokwelapha.

Imikhiqizoikhasi linikeza ulwazi oluningiliziwe mayelana nalezi zindlela zokwelapha.

Ukulinganisela kwamaplatelet akulawulwa kuphela ngokukhiqizwa kodwa nangokususwa kwamaplatelet asekhulile noma angasebenzi. Impilo ejwayelekile yamaplatelet isilinganiso sezinsuku ezingu-7 kuye kweziyi-10, ngemuva kwalokho asuswa ikakhulukazi yi-reticuloendothelial system, ikakhulukazi e-spleen nase-liver. Ama-macrophages aqaphela izinguquko ku-platelet membrane glycoproteins kanye nokuchayeka kwe-phosphatidylserine njengezimpawu zokususwa.

I-thrombopoietin feedback loop iqonda ubukhulu bamathambo ngokubopha kwe-TPO kumamukeli e-platelet c-Mpl. Amaplatelet ajikeleza e-TPO eboshiwe, anciphisa ngempumelelo ukugxila kwe-TPO yamahhala lapho izinombolo zamathambo ziphezulu, okunciphisa ukukhiqizwa kwamathambo okwengeziwe. Ngokuphambene, ukwehla kwezinombolo zamathambo kuholela ekwandeni kokutholakala kwe-TPO, kukhuthaza umnkantsha ukuthi ugcwalise amathambo.

Ukuphazamiseka ezindleleni zokususwa kwamathambo kungaba nomthelela ku-thrombocytopenia noma i-thrombocytosis, okwenza kube nzima ukuphathwa kwezinkinga zegazi. Ukuqonda lezi zinqubo kubalulekile ekuthuthukiseni imikhuba eqondisiwe elinganisa ukukhiqizwa nokususwa kwamathambo.

Ukwelula kwamaplatelet kuhilela izinguquko zamakhemikhali nezokwakheka ezikhombisa ukususwa kwawo ekujikelezeni kwegazi. Amaplatelet asekhulile abonisa ukwehliswa komsebenzi we-metabolic, ukuguquka kokwakheka kwe-membrane, nokudalulwa kwezimpawu ezithi “eat-me” njenge-phosphatidylserine, ezikhuthaza ukudliwa ngama-macrophages.

Ucwaningo lubonisa ukuthi ukucindezeleka kwe-oxidative nezimo zokuvuvukala kukhulisa ukuguga kwamaplatelet, kunciphisa isikhathi sawo sokuphila futhi kungaholela ku-thrombocytopenia. Le nqubo yokuguga ihlobene kakhulu nokusebenzisana kwesistimu yokuzivikela komzimba, njengoba amaplatelet agugile angathinta izindlela zokuvuvukala nokuvuselelwa kwamangqamuzana omzimba.

Izindlela zokwelapha ezihlanganisa indlela ye-thrombopoietin zisiza ukugcina inani lamaplatelet naphezu kokwanda kokususwa okuhambisana nokuguga noma isifo. Ngokukhuthaza ukukhiqizwa kwamaplatelet, imithi ye-thrombopoietin ebuyiselwe kabusha ilungisa ukulahleka futhi ibuyisele umsebenzi wokumisa igazi.

Ngaphandle kwendima yayo ekwakheni igazi, i-thrombopoietin ithonya izimpendulo zomzimba zokuzivikela. Ukuthumela isignali kwe-TPO receptor kuthonya umsebenzi wama-megakaryocyte nama-platelet, alawula ukuzivikela komzimba okungokwemvelo nokuvuvukala. Ama-platelet abamba iqhaza ngokusebenzayo ekugadweni komzimba ngokuxhumana nama-leukocyte, ukukhulula ama-cytokine, nokufaka isandla ekuvikelweni kwezifo.

Izimo ezizenzakalelayo ezifana ne-immune thrombocytopenia (ITP) zihlanganisa ama-antibody aqondise ama-platelet, okuholela ekususweni kwawo nasekwancipha kwezibalo zawo. Abathuthukisi be-thrombopoietin receptor, okuhlanganisa namafomu e-TPO aphindaphindwe kabusha, seba yizindlela zokwelapha ezibalulekile ku-ITP ngokukhuthaza ukukhiqizwa kwama-platelet naphezu kokucekelwa phansi okuqhubekayo okubangelwa umzimba.

Umkhiqizo we-rhTPO we-Stellar Biotech Limited, i-TPIAO, ukhonjiswa ngokwelashwa kwe-ITP engapheli neqhubekayo, usekela ukululama kwama-platelet nokunciphisa ubungozi bokopha ezigulini ezingaphenduli ezindleleni zokwelapha ezijwayelekile.

Ukuze uthole ulwazi olwengeziwe, vakashela i-Ukusekela ikhasi.

I-Thrombocytopenia, ebonakala ngokuba namazinga amaplatelet aphansi kunezinga elivamile, ingavela ekukhiqizeni okuncishisiwe, ukubhujiswa okwandisiwe, noma ukugcinwa kwamaplatelet. Ama-recombinant thrombopoietin nama-thrombopoietin receptor agonists ashintshe kakhulu ukwelashwa ngokuqondisa ukukhuthaza umnkala ukuthi wandise ukuphuma kwamaplatelet.

Izicelo zokwelapha zihlanganisa ukwelashwa kwe-chemotherapy-induced thrombocytopenia, i-aplastic anemia, ne-immune thrombocytopenia. Lezi zinto zithuthukisa imiphumela yeziguli ngokunciphisa izinkinga zokopha nokunciphisa isidingo sokudluliselwa kwamaplatelet.

Umkhiqizo we-Stellar Biotech Limited i-TPIAO ufanekisela ukuguqulwa okuphumelelayo kwe-thrombopoietin biology emithini ephumelelayo. Unikeza indlela esheshayo, elawulwayo, futhi ehambisana nemithetho yokwandisa inani lama-platelet, eliwusizo ezigulini ezidinga ukululama okuthuthukisiwe kwama-platelet.

Ucwaningo oluqhubekayo luyaqhubeka nokuhlola imininingwane ye-molecular yezindlela zokudlulisa isignali ze-thrombopoietin, ukwakheka kwamaplatelet, kanye nezinqubo zokususwa. Izifundo ezivelayo zigxile ekusebenzelaneni phakathi kwe-thrombopoiesis kanye nokulawulwa komgudu womgudu womgudu, ukuguga, kanye nezifo zokuvuvukala.

Ukusungulwa kobuchwepheshe be-recombinant thrombopoietin, ukuhlonza izinto ezibonakalisa izifo, kanye nokuhlela izakhi zofuzo kunikeza ithemba ngemithi eyenzelwe ngabanye ebhekana nezinkinga zamaplatelet. Ngaphezu kwalokho, ukuqonda imiphumela yesikhathi eside ye-thrombopoietin modulation ekulinganiseni kwesistimu yokuzivikela komzimba kuhlala kuyindawo ebalulekile yocwaningo.

I-Stellar Biotech Limited ihlala izibophezele ekusekeleni ukusungulwa kwezokwelapha kanye nentuthuko kwezempilo ngohlu lwayo oluphelele lwemikhiqizo namasevisi. Vakashela i-Isevisiikhasi ukuze ufunde kabanzi ngeminikelo yabo ezixazululweni zezempilo.

Umdwebo obonisa indlela ye-thrombopoietin elawula ukukhiqizwa nokususwa kwamathambo emnkantshweni nasemgqeni wegazi.

Ngokufingqiwe, indlela ye-thrombopoietin ibalulekile ekugcineni ukulingana kwamaplatelet nokusekela imisebenzi yokuzivikela komzimba. Ukuqhubeka ekuqondeni le ndlela kuye kwakhuthaza ukuthuthukiswa kwezindlela zokwelapha eziphumelelayo ze-thrombocytopenia nezifo ezihlobene nayo. Ngemikhiqizo emisha efana ne-recombinant human thrombopoietin, i-Stellar Biotech Limited idlala indima enkulu ekuthuthukiseni ukunakekelwa kweziguli nasekuthuthukiseni impilo ye-hematological emhlabeni jikelele.