As Japan ap­proves a stem cell treat­ment for spinal cord in­juries in a land­mark — if lit­tle no­ticed — de­ci­sion, ex­perts around the world have voiced con­cerns that un­der­score the trou­ble that still plague first-gen stem cell ther­a­pies. Com­ment­ing at the re­quest of Na­ture News, 10 spe­cial­ists in stem cell sci­ence or spinal cord in­juries poke holes in the small clin­i­cal tri­al that formed the ba­sis of the con­di­tion­al ap­proval, ques­tion­ing both the ef­fi­ca­cy and safe­ty of the treat­ment. The ther­a­py, Stemirac, in­volves ex­tract­ing mes­enchy­mal stem cells from a per­son who suf­fered from a spinal cord in­jury, grow­ing about 50 mil­lion to 200 mil­lion of them in a lab, then in­tra­venous­ly in­fus­ing the MSCs back in­to the pa­tient with­in 40 days of the in­jury. Ex­act­ly how it works to re­pair dam­age to the spinal cord is a bit of a black box now: Re­searchers led by pro­fes­sor Os­amu Hon­mo at Sap­poro Med­ical Uni­ver­si­ty be­lieve it might have to do with re­duc­ing in­flam­ma­tion, pro­tect­ing ex­ist­ing neu­rons or turn­ing in­to nerve cells them­selves. Their be­lief is based on an un­pub­lished 13-pa­tient tri­al, which saw 12 of them “im­prove by at least one lev­el on the Amer­i­can Spinal In­jury As­so­ci­a­tion im­pair­ment scale, an in­ter­na­tion­al­ly rec­og­nized sys­tem that ranks peo­ple’s abil­i­ty to con­tract mus­cles and sense touch on parts of the body,” Na­ture News re­port­ed. Skep­tics, how­ev­er, re­main leery. With­out a dou­ble-blind tri­al de­sign, there’s no way to prove that the im­prove­ments weren’t due to nat­ur­al heal­ing and phys­i­cal re­ha­bil­i­ta­tion in the months af­ter an in­jury, Bruce Dobkin, a neu­rol­o­gist at the Uni­ver­si­ty of Cal­i­for­nia, Los An­ge­les, told Na­ture News. “This tri­al, as de­signed, can­not re­veal ef­fi­ca­cy,” he said, adding the claim that the MSCs con­vert­ed to neu­rons in the tri­al is al­so a red flag. An­oth­er rea­son to be cau­tious, ac­cord­ing to NIH stem cell re­searcher Pamela Robey: The fact, shown in pre­vi­ous re­search, that MSCs in­fused in­tra­venous­ly tend to get trapped in the lungs “makes it dif­fi­cult to see how they can be ef­fec­tive in the spinal cord.” Masanori Fukushi­ma, a gov­ern­ment-fund­ed ad­vis­er to the project, has stood by Hon­mo’s work, em­pha­siz­ing that some pa­tients in the tri­al were too se­vere­ly in­jured to have had achieved nat­ur­al heal­ing. When the med­ical equip­ment man­u­fac­tur­er Nipro Corp be­gins sell­ing Stemirac, it can mark some long await­ed ac­tiv­i­ty for re­gen­er­a­tive med­i­cine in the mar­ket­place af­ter years of de­lays and dis­ap­point­ments. But it’s not nec­es­sar­i­ly the en­try that the in­dus­try — which is now ex­plor­ing next-gen, of­ten off-the-shelf, stem cell-based ther­a­pies for di­a­betes, Crohn’s dis­ease and graft ver­sus host dis­ease among oth­ers — has been look­ing for.
A stem cell therapy aimed at helping patients recover from spinal cord injuries has been greenlit in ef­fi­ca­cy. By extracting mesenchymal stem cells from injured individuals, growing 50-200 million of them in the lab, and then intravenously reintegrating them into the patient, Stemirac is meant to aid in injury recovery. After a small clinical trial, the decision was made to conditionally approve the method. However, specialists have raised concerns over the efficacy of the therapy. Little is known about how recovery is helped by the treatment, and the findings of the unpublished 13-person trial have been flagged as insufficient.