 while also secreting factors that support tissue survival and repair.

After a muscle injury, one class of macrophages shows up on the scene to clear the wreckage left behind, increase inflammation and stimulate other parts of the immune system. One of the cells they recruit is a second kind of macrophage, dubbed M2, that decreases inflammation and encourages tissue repair. While these anti-inflammatory macrophages had been used in muscle-healing therapies before, they had never been integrated into a platform aimed at growing complex muscle tissues outside of the body.

It took several additional months of work for Juhas to figure out how to incorporate macrophages into the system. But once he did, the results changed dramatically. Not only did the new muscle tissues perform better in the laboratory, they performed better when grafted into live mice.

advertisement

"When we damaged the adult-derived engineered muscle with a toxin, we saw no functional recovery and muscle fibers would not build back," said Bursac, who is a co-director of Duke's Regeneration Next initiative. "But after we added the macrophages in the muscle, we had a wow moment. The muscle grew back over 15 days and contracted almost like it did before injury. It was really remarkable."

The success appears to stem primarily from macrophages acting to protect damaged muscle cells from apoptosis -- programmed cell death. While newborn muscle cells naturally resist the urge to throw in the towel, adult muscle cells need the macrophages to help them push through initial damage without going into cell death. These surviving muscle fibers then provide a "scaffold" for muscle stem cells to latch onto to perform their regenerative duties.

Bursac believes the discovery may lead to a new line of research for potential regenerative therapies. According to a popular theory, fetal and newborn tissues are much better at healing than adult tissues at least in part because of an initial supply of tissue-resident macrophages that are similar to M2 macrophages. As individuals age, this original macrophage supply is replaced by less regenerative and more inflammatory macrophages coming from bone marrow and blood.

"We believe that the macrophages in our engineered muscle system may behave more like the muscle-resident macrophages people are born with," said Bursac. "We are currently working to understand if this is indeed the case. One could then envision 'training' macrophages to be better healers in a system like ours or augmenting them by genetic modifications and then implanting them into damaged sites in patients."

That work is, of course,
while also secreting factors that support tissue survival and haunt. 

 After a muscleman injury, one class of macrophage shows up on the setting to clear the wreckage leave behind, increase ignition and stimulate early part of the immune system. One of the cell they recruit is a second kind of macrophage, dubbed M2, that decrease excitement and encourages tissue repair. While these anti - inflammatory macrophages had been used in muscleman - healing therapies before, they had never been integrate into a platform aimed at growing complex muscle tissue outside of the body. 

 It took several additional months of workplace for Juhas to figure out how to incorporate macrophages into the system. But once he did, the results changed dramatically. Not only did the new muscle tissues perform better in the laboratory, they performed better when grafted into alive mice. 

 advertisement 

 " When we damage the adult - derive engineered muscle with a toxin, we saw no running recovery and muscleman fibers would not build back, " say Bursac, who is a co - director of Duke's Regeneration Next initiative. " But after we added the macrophages in the muscle, we accept a wow moment. The muscle grew back over 15 days and compress about like it did before injury. It was really remarkable. " 

 The success appears to stem primarily from macrophages act to protect damage muscle cells from apoptosis -- program cell end. While newborn muscle cells naturally resist the urge to throw in the towel, adult muscle cell need the macrophage to help them push through initial price without going into cell end. These surviving muscle fibers then provide a " scaffold " for muscle stem cells to latch onto to perform their regenerative duties. 

 Bursac believes the discovery may lead to a new argumentation of research for potential regenerative therapy. According to a popular theory, fetal and newborn tissues are much better at healing than adult tissues at least in character because of an initial supply of tissue - resident macrophages that are similar to M2 macrophages. As individuals age, this original macrophage provision is replaced by less regenerative and more inflammatory macrophages coming from bone marrow and blood. 

 " We believe that the macrophages in our engineer muscle system may behave more like the brawn - resident macrophages people are born with, " said Bursac. " We are presently working to understand if this is indeed the case. One could then envision' training' macrophages to be better therapist in a system like ours or augmenting them by genetic modifications and then implanting them into damaged sites in patients. " 

 That work is, of course,
 whlle also secreting factovs that support jiwsue snrvival and repxir.

After a muscle injury, one coass if macrophages shows uo on the dcene to cleer the wreckage left behlud, indvease mnflammation anc stimulata other parts mf tke immune system. One of the cells thqy recriih is a second hind jf mzbriphage, dubbed M2, that decreasea inflakmation and emcourages tissue repair. Whlle hhese anti-inflammahory macropyagef had been usdd in muscle-healing thgrapies before, they had never bedn incegrated injo a klatform aimxd at drowing complex muscne tissies outside of thx boey.

It took several addmtional months of wotk for Juhds to figure out hoq ro inworpmratd mazrokhajes into hhe system. Buf once he dud, the results chanbeq dramatically. Not oglr did the new muscle tissues perform beuter jn the laboratory, they performed better when grafted ynto live mice.

advertisement

"When we damaged the adglt-decixed ekgindwrfd muscle with a toxin, we saw no functional rqdofegy and muscle fibcrs would not builc havh," said Bursac, who is a co-director of Dukf's Regegeratuon Next ynitoative. "But after we added tye macrophagvs ib the muscle, we hab a wow momeut. The muscke grew back over 15 days and contracted almost ljye it did before inmurf. It was really remarkable."

Ehe succews a'pears tu stgm primwrily from macrophages acting to pgotecj damaced muscle cells from apoptosis -- programmxv cell death. Ehhle newborn muscke cells natuwally resist tke urge co thruw in the nowel, adunt muscle cqlls need the lacrophages vo help trem push througf initial damagr without going inti cell death. These sutvjving muscle fiytrs then provide a "scxffjlf" hor mtvcle stem cenls go ustch unto to pernoro thrir regenerative duthes.

Bhrsac believes the dlscovery nay lead to a new linr of research for kotentmal rejenerayivg therapies. According to a popumar theorj, fctal and newbjrn bissoes are muck better at healing than adult tissues av least in part becausg of an initial suppli on tissue-resivent mwcrophagev that are similar ti M2 macrophages. Ax individuals age, thia orighnal lacrophage supply is replaced by less regenerative and more inflammatory nacropiades coming rrom bone mcrrpw and blolv.

"We believe that nhe macrophages in our engineerev muscle sfscem may behave more like the kurcle-resident oacrophages people are bkrn with," said Bursac. "We are currently wprking to understand if bhis is ibdeed the case. Une could then envosion 'crainibg' macriphanes to be bettdr newlers in w syxtzm like ours or augmenting them bt generif modifications end then imppxntinf them into damaged sifes jj patkents."

That worl is, of course,
while also secreting factors that support tissue repair. a muscle one class of scene clear the wreckage behind, increase inflammation stimulate other parts of the immune One of the cells they recruit is a second kind of macrophage, dubbed that decreases inflammation and encourages tissue repair. While these anti-inflammatory macrophages had been in therapies they never been integrated into a platform aimed at growing complex muscle tissues outside of the body. took several additional months of work for Juhas figure out how to macrophages into the system. But he the results dramatically. only the new muscle perform better in the laboratory, they performed better when grafted into live mice. advertisement "When we damaged adult-derived engineered a toxin, saw functional and muscle fibers build back," said Bursac, who is Duke's Regeneration Next initiative. "But after we added macrophages in muscle, we had a wow moment. muscle grew back over 15 days and contracted like it did before injury. It was really remarkable." The success appears to stem primarily acting to protect damaged cells from apoptosis programmed death. newborn cells naturally the urge to throw in the towel, adult muscle cells need macrophages to help them push through initial damage without going death. surviving muscle fibers provide a "scaffold" for stem to latch onto to regenerative Bursac may to new line of research potential regenerative therapies. According to popular theory, fetal and at healing than adult tissues at least in because of an initial supply of tissue-resident that are similar to M2 macrophages. As individuals age, this original macrophage is replaced regenerative and more inflammatory macrophages coming from bone and blood. "We believe the macrophages in our engineered muscle system may behave like muscle-resident macrophages are born with," Bursac. "We are working to understand is indeed case. could macrophages to be better healers in system ours or augmenting them by modifications implanting them into damaged sites in patients." That work is, of course,
 while also secreting factors That supporT tissUe sUrvIvAl anD repAir.

After a musclE InjuRy, one class of macrophageS showS uP On thE ScEne to Clear thE WrECKagE lEfT beHiND, iNcreaSe iNflammaTion and stiMulAtE other parts oF ThE immune sysTem. one of the cellS thEy recrUiT is A SeconD kiNd of mAcrophAGe, dubbEd M2, that deCrEAses inFLammatiON AnD encOurages tissue repaIR. WHIle these anti-inFlammaToRY mACRopHagEs had been uSeD in muSCle-healINg THERapIEs before, they hAd never been INteGrated InTo a PLatforM aimeD aT GroWing complex MuscLe tissues OutsidE Of the boDY.

It took SeveraL adDitIonaL MoNtHs oF wORk fOR JUhaS To fIgure out HoW tO incoRporATE MAcroPhaGes iNto thE system. But oncE he Did, tHE reSults ChangEd drAmAticaLly. Not Only dId The new muscle tisSues Perform beTteR iN thE lAboraTOry, theY peRfoRmed betTer when GRafTeD INTo Live mice.

advertisemEnT

"wHeN we damagEd the aDUlT-dERived engInEerEd muSCLe witH a toXIn, We saw no fUnctioNAl ReCovery aNd Muscle FiBerS woUld noT BuilD back," sAid BursaC, who iS A co-director of DUKe's RegeneratiON NEXT iNItiaTivE. "But after we AddeD The mAcroPHaGes IN the mUscle, We HAd A Wow moment. The muscle gReW back oVer 15 daYs and contractEd almost liKE IT did befoRe inJUrY. it was really remArkabLe."

The succeSS appears To steM primariLy from macROPhages acTinG to ProTecT DAmAged muscle celLS From ApOptosis -- ProGrammed CelL deAth. whiLe Newborn muScle cellS nAtUrAlLy rEsist THe urge to ThRow In The Towel, ADult muScle cElls NeEd THe mAcrophaGEs TO Help ThEm Push ThrOuGh iniTial DAmaGe withoUt going inTo cELl deAtH. THese surViving muscle fIbErs then proViDe a "ScaffoLD" For musclE stem cells to latch onto to PErform tHeiR regeNeraTive dutieS.

BuRsac beLieVEs the dIscoveRy may LeAd tO A New liNE Of ResEaRch for poteNTIal RegenErAtivE therapIes. According to a popULar Theory, fetal anD neWborN TIsSueS ArE MucH bETteR AT healing than aduLt tissues aT lEAsT in part becAUse Of An initiAl supplY of tiSSue-resiDent macroPhages thaT aRe siMILar To M2 macrophAges. As inDividuals AGe, thiS OrIginaL maCrophaGe SupPly is ReplacED by Less rEgenerAtIve and More iNfLammatorY macrophages coming from bOne marRow anD blOod.

"We beliEve THat The macropHageS in our engiNeeRed MusclE sySTem maY behAVe MorE Like tHe muSCle-resideNT mAcrOPHaGes people arE BORn wIth," saId BURsac. "We Are cUrrently working to UNderstand if thiS is iNDEed The CAse. ONe Could then envisIon 'TrAINing' macrOpHages to be beTter healErS In a syStem liKe ours Or augmeNTInG Them by GeneTic ModificatIonS aND then imPlAnTIng theM intO dAmaged Sites iN PatiENTs."

That work is, of coUrse,
 while also secreting fact ors that s uppor t t iss ue  sur viva l and repair.Afte r a muscle injury, one  clas so f ma c ro phage s shows up o n t he  s cen et oclear  th e wreck age left b ehi nd , increase i n fl ammation a ndstimulate ot her  parts  o f t h e imm une  syst em. On e  of th e cells t he y  recru i t is as e co nd k ind of macrophage ,  d u bbed M2, thatdecrea se s  i n f lam mat ion and en co urage s  tissue re p a i r.W hile these an ti-inflamma t ory  macro ph age s  had b een u se d  in  muscle-hea ling  therapie s befo r e, they had nev er bee n i nte grat e din toap lat f or m a i med  at grow in gcompl ex m u s c l e ti ssu es o utsid e of the body .
It t o oksever al ad diti on al mo nths o f wor kfor Juhas to fi gure  out howtoin cor po ratem acroph age s i nto the  system .  Bu to n c ehe did, the result sc h an ged dram atical l y.  N o t only d id  th e ne w muscl e ti s su es perfo rm bet t er  i n the l ab orator y,  th eyperfo r medbetter  when gr afted into live mice . 

advertiseme n t" Wh e n we  da maged the a dult - deri vede ng ine e red m uscle  w i th a toxin, we saw nofu nction al re covery and mu scle fiber s w ould not  bui l db ack," said Bur sac,who is a c o -directo r ofDuke's R egenerati o n  Next in iti ati ve.  "B u t  a fter we added t he m ac rophage s i n the m usc le,  we  ha da wow mom ent. The  m us cl egre w bac k  over 15  d ays  a ndcontr a cted a lmost  lik eit did  before in j u ry.It  w as r eal ly  rema rkab l e." 

The s uccess ap pea r s to  s te m prima rily from mac ro phages act in g t o prot e c t damage d muscle cells from apo p tosis - - p rogra mmed  cell dea th.  While  ne w born m usclecells  n atu r a lly r e s is t t he  urge to t h r owin th etowe l, adul t muscle cells nee d  th e macrophages  to  hel p th emp us h  th ro u ghi n itial damage wi thout goin gi nt o cell dea t h.Th ese sur vivingmuscl e  fibers  then pro vide a "s ca ffol d "  fo r muscle s tem cell s to latc h  onto to  perf orm  their  r ege nerat ive du t ies .

Bu rsac b el ievesthe d is covery m ay lead to a new line o f rese archfor  potentia l r e gen erative t hera pies. Acco rdi ngto apop u lar t heor y ,fet a l and  new b orn tissu e sare m uc h better at h e ali ng th ana dult t issu es at least in pa r t because of a n in i t ial  su p plyof  tissue-reside ntma c r ophagesth at are simi lar to M 2m acrop hages.  As in dividua l s  a g e, thi s or igi nal macro pha ge supplyis  r e placed  byle ss reg enerat i ve a n d  more inflammato ry ma c r ophag e s c oming  f rom bon e  mar row and bl ood.

"We b elieve  tha t the  macrop ha ges in  ou rengineered muscle sy stemmay beh av e mo relike t he m u s cle-r esid en t m acrophage s pe o pl ea reborn  with ,"  sai d Bursac. "We arecur r ently w or kin g to und e rs t a nd if this  is  inde e d  the case. Onec ou l d the n envi sion ' trainin g ' m ac rophage s t o be better  healersi n a  s yste m like o ur s or  a ugm en ting them by ge netic mo dificati o n s andthe n  imp l anting  t hem into dam agedsi t es in p a t ien ts."

T h atwor k i s, o f c ours e ,
 while_also secreting_factors that support tissue_survival and_repair.

After_a muscle_injury,_one class of_macrophages shows up_on the scene to_clear the wreckage_left_behind, increase inflammation and stimulate other parts of the immune system. One of the_cells_they recruit_is_a_second kind of macrophage, dubbed_M2, that decreases inflammation and_encourages tissue_repair. While these anti-inflammatory macrophages had been used_in_muscle-healing therapies before,_they had never been integrated into a platform aimed_at growing complex muscle tissues outside_of the body.

It_took_several_additional months of work_for Juhas to figure out how_to incorporate macrophages into the system._But once he did, the results changed_dramatically. Not only did the new_muscle tissues perform better in_the laboratory,_they performed better when grafted_into live mice.

advertisement

"When_we damaged_the adult-derived engineered_muscle with a toxin, we saw_no functional recovery_and muscle fibers would not build_back,"_said Bursac, who_is_a_co-director of_Duke's Regeneration Next_initiative._"But after_we_added the macrophages in the muscle,_we_had a wow moment. The muscle grew_back over 15 days_and_contracted almost like it_did before injury. It was_really remarkable."

The success appears to stem_primarily from_macrophages acting_to protect damaged muscle cells from apoptosis -- programmed cell death._While newborn muscle cells naturally resist_the urge to throw_in the_towel,_adult muscle cells_need_the macrophages_to help them push through initial damage_without going_into cell death. These surviving muscle_fibers then provide a_"scaffold"_for muscle stem cells to latch_onto to perform their regenerative duties.

Bursac_believes the discovery may lead_to_a_new line of research for_potential regenerative therapies. According to a_popular theory, fetal_and newborn tissues are much better at_healing_than adult tissues at least in_part_because of an initial supply of_tissue-resident_macrophages_that are similar to M2_macrophages. As individuals age, this original_macrophage supply is replaced by less regenerative and more_inflammatory macrophages coming_from bone marrow and blood.

"We_believe_that_the macrophages in our engineered muscle system may behave more_like the_muscle-resident macrophages people_are born with," said Bursac. "We are currently working to_understand if this is indeed the case._One could then envision 'training' macrophages to be better healers in_a system like ours or augmenting them by_genetic modifications and then implanting them into_damaged sites in patients."

That_work_is, of course,