STEM CELLS: FRAM­ING THE FU­TURE OF HEALTH­CARE

Stem cells are be­lieved to have the abil­ity to di­vide with­out limit and to give rise to spe­cial­ized cells. Stem cell re­search is an ex­cit­ing yet com­plex and con­tro­ver­sial sci­ence. It holds the prom­ise of help­ing us bet­ter un­der­stand the most fun­da­men­tal p

BioSpectrum (Asia) - - Bio Content - Priyanka Ba­j­pai priyanka.ba­j­pai@mmac­tiv.com

Stem cells are be­lieved to have the abil­ity to di­vide with­out limit and to give rise to spe­cial­ized cells. Stem cell re­search is an ex­cit­ing yet com­plex and con­tro­ver­sial sci­ence. It holds the prom­ise of help­ing us bet­ter un­der­stand the most fun­da­men­tal pro­cesses of cel­lu­lar spe­cial­iza­tion and hu­man de­vel­op­ment, and many na­tions have there­fore in­vested heav­ily in stem cell re­search and its ap­pli­ca­tions. Stem cell re­search is one of the most ex­cit­ing ar­eas of the 21st cen­tury sci­ence and has the po­ten­tial to rev­o­lu­tion­ize the way we treat con­di­tions, in­clud­ing re­gen­er­a­tive dis­eases for which few ef­fec­tive treat­ments cur­rently ex­ist. There is a lot of hope in­vested in this field by re­searchers, gov­ern­ments and the gen­eral pub­lic.

Since the ad­vent of in­duced pluripo­tent stem cells (iPSC) through the No­bel lau­re­ate win­ning rev­o­lu­tion­ary work of Shinya Ya­manaka and col­leagues, the field of pluripo­tent stem cell re­search and cell ther­apy de­vel­op­ment has seen an ex­plo­sion in ac­tiv­ity. Pre­vi­ously, this area had been lim­ited to a few spe­cial­ized cen­tres that had ac­cess to and ex­per­tise in the cul­ture of hu­man pre-im­plan­ta­tion blas­to­cyst-de­rived em­bry­onic stem cells.

“It spurred Ja­pan, the coun­try where iPSC tech­nol­ogy emerged, into action with ded­i­cated gov­ern­ment sup­port, to be­come a leader in cell ther­apy de­vel­op­ment, hav­ing the ben­e­fit of re­gen­er­a­tive medicine for both the econ­omy and their aging pop­u­la­tion in mind,” says Thorsten

Gorba,

Trans­lat­ing Cen­ter Director, IQVIA Stem Cell Cen­ter.

Sci­en­tists are en­gaged in dis­cov­er­ing novel meth­ods to cre­ate hu­man stem cells. This is to ad­dress the in­creas­ing de­mand for stem cell pro­duc­tion for po­ten­tial in­ves­ti­ga­tion in disease man­age­ment. This fac­tor is cer­tainly ex­pected to ac­cel­er­ate the de­vel­op­ment of re­gen­er­a­tive medicine, thus driv­ing in­dus­trial growth. More­over, cel­lu­lar ther­a­pies are rec­og­nized as the next ma­jor ad­vance­ments in trans­form­ing health­care. Re­gen­er­a­tive medicine is one of the fastest grow­ing ther­a­peu­tic ap­pli­ca­tions of stem cells. It in­volves the us­age of in­no­va­tive med­i­cal ther­a­pies for the body to re­pair or re­place the dis­eased or dam­aged cells.

Stem cell re­search is de­vel­op­ing fast, with some ex­per­i­men­tal pluripo­tent stem cell treat­ments al­ready in clin­i­cal tri­als. Com­ment­ing on the ex­cit­ing ad­vance­ments in the field of stem-cell re­search in re­cent times, Gorba says, “The new ef­fec­tive gene edit­ing tech­nolo­gies will have a pro­found en­abling and en­hanc­ing ef­fect on stem cell and other cell ther­a­pies, in­clud­ing CAR-T (chimeric anti­gen re­cep­tor T-cell), im­mune-on­col­ogy (I-O) cancer treat­ments.”

Speak­ing on last year’s ap­provals of the Kym­riah and Yescarta I-O au­tol­o­gous CAR-T ther­a­pies for leukemias he says “the ap­provals have pro­vided a huge boost for the whole cell and stem cell ther­apy field, as ev­i­denced by suc­cess­ful stock mar­ket IPO launches and avail­abil­ity of in­vestor cap­i­tal, de­spite, strictly speak­ing, au­tol­o­gous T-cell treat­ments not be­ing stem cell ther­a­pies. How­ever, next gen­er­a­tion CAR-T and nat­u­ral killer (NK) cell al­lo­geneic, I-O ther­a­pies, de­rived from iPSC, are al­ready in the late pre­clin­i­cal stage and will en­ter clin­i­cal trial soon. These new I-O prod­ucts, aided by gene-edit­ing mod­i­fi­ca­tions, have the po­ten­tial to over­come lim­i­ta­tions of the cur­rent au­tol­o­gous CAR-T prod­ucts, e.g. lack of suc­cess in solid tu­mours, less side ef­fects and the abil­ity to ef­fec­tively counter tu­mour eva­sion strate­gies. In ad­di­tion, masspro­duced, “off-the-shelf” I-O cell prod­ucts will have sig­nif­i­cantly re­duced man­u­fac­tur­ing costs per pa­tient dose, will make wide-spread use and re­im­burse­ment in com­mon can­cers pos­si­ble.”

Chal­lenges and reme­dies

Reg­u­la­tory

Ac­tive de­bates are un­der­way to adapt reg­u­la­tory frame­works to ad­dress the spe­cific chal­lenges of de­vel­op­ing, stan­dard­iz­ing, and dis­tribut­ing cell-based ther­a­pies, while ad­vances in ba­sic re­search con­tinue to pro­vide a fuller un­der­stand­ing of how stem cells can be safely and ef­fec­tively used. Cell re­place­ment or trans­plan­ta­tion ther­a­pies are not the only ap­pli­ca­tion of stem cell re­search: al­ready the first steps are be­ing taken to­wards use of cells de­rived from pluripo­tent stem cells, in drug dis­cov­ery and test­ing.

The field holds the po­ten­tial to rev­o­lu­tion­ize the way hu­man dis­eases are treated, and many na­tions have there­fore in­vested heav­ily in stem cell re­search and its ap­pli­ca­tions. How­ever, hu­man stem cell re­search is also con­tro­ver­sial with many eth­i­cal and reg­u­la­tory ques­tions that im­pact a na­tion’s poli­cies. Tech­ni­cal

Con­trol­ling stem cells isn’t easy. Both adult and em­bry­onic stem cells present chal­lenges. Though stem cells ex­ist in adult tis­sue, they’re not present in great num­bers, so they can be hard to find and to ex­tract for growth.

Work­ing with em­bry­onic stem cells has its own chal­lenges, too. Though they’re eas­ier to grow into batches of un­spe­cial­ized cells, re­searchers need to bet­ter un­der­stand how these cells re­pro­duce in

“The ap­provals have pro­vided a huge boost for the whole cell and stem cell ther­apy field, as ev­i­denced by suc­cess­ful stock mar­ket IPO launches and avail­abil­ity of in­vestor cap­i­tal, de­spite, strictly speak­ing, au­tol­o­gous T-cell treat­ments not be­ing stem cell ther­a­pies. How­ever, next gen­er­a­tion CAR-T and nat­u­ral killer (NK) cell al­lo­geneic, I-O ther­a­pies, de­rived from iPSC, are al­ready in the late pre­clin­i­cal stage and will en­ter clin­i­cal trial soon. These new I-O prod­ucts, aided by ge­need­it­ing mod­i­fi­ca­tions, have the po­ten­tial to over­come lim­i­ta­tions of the cur­rent au­tol­o­gous CAR-T prod­ucts, e.g. lack of suc­cess in solid tu­mours, less side ef­fects and the abil­ity to ef­fec­tively counter tu­mour eva­sion strate­gies.” - Thorsten Gorba, Trans­lat­ing Cen­ter Director, IQVIA Stem Cell

Cen­ter

the lab­o­ra­tory, and how to re­li­ably trig­ger them to dif­fer­en­ti­ate into the spe­cific types of cells needed. There are also concerns that trans­planted stem cells may not work in con­junc­tion with the tis­sue of the per­son re­ceiv­ing them.

Be­cause of the tech­ni­cal lim­i­ta­tions in­volved in us­ing adult stem cells, em­bry­onic stem cells are gen­er­ally pre­ferred by stem cell re­searchers. How­ever, we find eth­i­cal ques­tions per­tain to the use of em­bry­onic stem cells.

The field of stem cell and gen­er­ally cell ther­a­pies is still young. Con­se­quently, most of the com­pa­nies in it are young and small emerg­ing bio­pharma, too. Gorba be­lieves that there are some se­ri­ous ef­forts needed to cre­ate, study, and ul­ti­mately use stem cells and their off­spring in early-phase ex­per­i­men­tal hu­man ther­a­pies and bring the most promis­ing ther­a­pies from the lab into clin­i­cal tri­als in peo­ple.

“Of­ten these are re­cent univer­sity spin-outs with few em­ploy­ees that know their sci­ence well, but lack the ex­per­tise and ex­pe­ri­ence in for­mal drug de­vel­op­ment. When seek­ing help from in­de­pen­dent con­sul­tants, emerg­ing cell ther­apy com­pa­nies will of­ten have to grap­ple with con­fus­ing, or even con­tra­dic­tory and non-com­pat­i­ble pieces of ad­vice. To make their re­search ac­tiv­i­ties run smoothly, IQVIA has come up with an in­te­grated as­set de­vel­op­ment ser­vice, in which a cross-func­tional team of drug de­vel­op­ment and cell ther­apy ex­pe­ri­enced ex­perts work to­gether with the client to de­velop, a risk-bal­anced ap­proach for the great­est like­li­hood of prod­uct suc­cess, in the fastest and most cost-ef­fi­cient way. This in­te­grated ap­proach plans and con­sid­ers pre­clin­i­cal and clin­i­cal de­vel­op­ment, as well as man­u­fac­tur­ing and reg­u­la­tory strat­egy to­gether. An im­por­tant tool for this plan is the gen­er­a­tion of a tar­get prod­uct pro­file (TPP), which tries to de­fine the even­tual la­bel of the ap­proved prod­uct, and spec­i­fies in­di­ca­tion and pa­tient pop­u­la­tion se­lec­tion. A health eco­nomic out­come re­search (HEOR), will pre­dict the mar­ket size for the prod­uct and its like­li­hood to be ob­tain com­mer­cially vi­able re­im­burse­ment. Hence, such an as­sess­ment will be of great value for de­vis­ing a man­u­fac­tur­ing strat­egy that will be able to meet de­mand sus­tain­ably, at a rea­son­able cost of goods. Once a ther­apy can­di­date reaches clin­i­cal tri­als, en­rol­ment pro­jec­tion and site se­lec­tion op­ti­miza­tion, will avoid costly de­lays in en­rol­ment and timely trial com­ple­tion for com­pa­nies with a lim­ited fi­nan­cial run­way.”

Gorba, who is op­ti­mistic of the fu­ture of stem cell re­search in the com­ing years, con­cludes, “Dur­ing the com­ing 10 years, the first wave of stem cell ther­a­pies that we will see pro­gres­sion from clin­i­cal tri­als to the mar­ket and gen­eral pa­tient pop­u­la­tions, are tis­sue-de­rived stem cells, with the ma­jor­ity of near fu­ture ap­proved prod­ucts ex­pected to fall into the two dom­i­nant cell type cat­e­gories mes­enchy­mal stem cells (MSC) and gene-mod­i­fied hematopoi­etic stem cells (GM-HSC). Next, the iPSC rev­o­lu­tion will then man­i­fest it­self with a sec­ond wave of pluripo­tent stem cell-de­rived re­gen­er­a­tive medicine prod­uct clin­i­cal tri­als, and per­haps the first cou­ple of ap­provals.

These cell ther­apy prod­ucts will pro­vide func­tional re­place­ment of lost and im­paired cell types with the aim of true re­gen­er­a­tion and restora­tion; set­ting back the clock on dis­eases, rather than just halt­ing their pro­gres­sion. In ad­di­tion to pure cell ther­a­pies, tis­sue en­gi­neer­ing 2.0, based on stem and pro­gen­i­tor cell tech­nolo­gies, will make a re­vival”.

Much re­mains to be learned about stem cells, in­clud­ing po­ten­tial haz­ards. Real ap­pli­ca­tions, for the most part, are still years away. But if progress with blood and bone mar­row trans­plants is any in­di­ca­tion, stem cell re­search may some­day help many peo­ple. These cells may sig­nif­i­cantly ad­vance disease treat­ment and ex­pand hu­man knowl­edge of the body’s ba­sic pro­cesses.

Newspapers in English

Newspapers from India

© PressReader. All rights reserved.