I-PRP yanamhlanje: "I-PRP yezonyango"
Kwiminyaka eyi-10 edlulileyo, isikimu sonyango se-PRP senziwe utshintsho olukhulu.Ngophando lovavanyo kunye nolweklinikhi, ngoku sinokuqonda okungcono kweplatelet kunye nezinye iiseli zefiziyoloji.Ukongezelela, uvavanyo oluninzi olusemgangathweni olucwangcisiweyo oluphezulu, uhlalutyo lwe-meta kunye nezilingo ezilawulwa ngokungahleliwe zibonise ukusebenza kwe-PRP biotechnology kwiinkalo ezininzi zonyango, kuquka i-dermatology, utyando lwentliziyo, utyando lweplastiki, utyando lwamathambo, ulawulo lweentlungu, izifo zomgogodla, kunye neyeza lezemidlalo. .
Uphawu lwangoku lwe-PRP lugxininiso olupheleleyo lweplatelet, olutshintshayo kwinkcazo yokuqala ye-PRP (kubandakanywa ukuxinwa kweplatelet ephezulu kunexabiso lesiseko) ukuya ngaphezu kwe-1 × 10 6 / µ L okanye malunga namaxesha angama-5 ubuncinci boxinzelelo lweplatelet kwiiplatelet ukusuka isiseko.Kuphononongo olubanzi nguFadadu et al.Iinkqubo ze-33 ze-PRP kunye neeprotokholi zavavanywa.Ubalo lweplatelet yolungiselelo lokugqibela lwe-PRP oluveliswe zezinye zezi nkqubo luphantsi kunolo lwegazi lilonke.Bachaza ukuba i-platelet factor ye-PRP inyuke iphantsi njenge-0.52 kunye ne-single spin kit (Selphyl®).Ngokwahlukileyo, i-double-rotation EmCyte Genesis PurePRPII ® I-concentration yeplatelet eveliswa sisixhobo iyona ephezulu (1.6 × 10 6 /µL) .
Ngokucacileyo, i-in vitro kunye neendlela zezilwanyana ayiyona ndawo ifanelekileyo yophando yotshintsho oluyimpumelelo kuqheliselo lweklinikhi.Ngokufanayo, uphononongo lokuthelekisa isixhobo aluxhasi isigqibo, kuba lubonisa ukuba i-concentration yeplatelet phakathi kwezixhobo ze-PRP ihluke kakhulu.Ngethamsanqa, ngeteknoloji esekelwe kwiproteomics kunye nohlalutyo, sinokunyusa ukuqonda kwethu imisebenzi yeseli kwi-PRP echaphazela iziphumo zonyango.Ngaphambi kokufikelela kwimvumelwano kumalungiselelo e-PRP asemgangathweni kunye nokuqulunqwa, i-PRP kufuneka ilandele iifomyula ze-PRP zeklinikhi ukukhuthaza iindlela ezinkulu zokulungisa izicubu kunye neziphumo zeklinikhi eziqhubekayo.
Ifomula yekliniki ye-PRP
Okwangoku, i-PRP yeklinikhi esebenzayo (C-PRP) ibonakaliswe njengento eyinkimbinkimbi ye-autologous multicellular components kwi-plasma encinci yevolumu efunyenwe kwinxalenye yegazi le-peripheral emva kwe-centrifugation.Emva kwe-centrifugation, i-PRP kunye ne-non-platelet cell components ingafunyanwa kwisixhobo soxinaniso ngokwee-cell densities ezahlukeneyo (apho i-platelet density iphantsi).
Sebenzisa i-PurePRP-SP ® izixhobo zokwahlula i-Cell density (EmCyte Corporation, Fort Myers, FL, USA) yayisetyenziselwa igazi elipheleleyo emva kweenkqubo ezimbini ze-centrifugation.Emva kwenkqubo yokuqala ye-centrifugation, icandelo legazi elipheleleyo lahlulwa libe ngamacandelo amabini asisiseko, i-platelet (i-lean) i-plasma suspension kunye ne-red blood cell layer.Kwi-A, inyathelo lesibini le-centrifugation ligqityiwe.Umthamo we-PRP wangempela unokukhutshwa kwisicelo sesigulane.Ukwandiswa kwe-B kubonisa ukuba kukho i-multi-component erythrocyte sedimentation sedimentation layer emdaka (emelwe ngumgca oluhlaza) ezantsi kwesixhobo, equlethe ukugxila okuphezulu kweeplatelet, i-monocytes kunye ne-lymphocytes, ngokusekelwe kwi-gradient yoxinaniso.Kulo mzekelo, ngokwe-C-PRP yokulungiselela iprotocol kunye ne-neutrophils embi, ipesenti encinci ye-neutrophils (<0.3%) kunye ne-erythrocytes (<0.1%) iya kukhutshwa.
Igranule yePlatelet
Kwisicelo sokuqala se-PRP yeklinikhi, i-α- Granules iyona nto ichazwe ngokuqhelekileyo isakhiwo sangaphakathi seplatelet, kuba ziqulethe izinto ezidibeneyo, inani elikhulu le-PDGF kunye nabalawuli be-angiogenic, kodwa banomsebenzi omncinci we-thrombogenic.Ezinye izinto ziquka i-chemokine engaziwa kakhulu kunye ne-cytokine components, ezifana ne-platelet factor 4 (PF4), iprotheni esisiseko yangaphambi kweplatelet, i-P-selectin (i-activator ye-integrin) kunye ne-chemokine RANTES (ilawulwa ngokusebenza, ukuvakalisa iiseli ze-T eziqhelekileyo kwaye mhlawumbi ukufihla).Umsebenzi opheleleyo wale nxalenye yegranule yeplatelet kukufumana kunye nokwenza ezinye iiseli zomzimba zisebenze okanye kubangele ukudumba kweeseli ze-endothelial.
Izinto ezixineneyo zegranular ezifana ne-ADP, i-serotonin, i-polyphosphate, i-histamine kunye ne-adrenaline zisetyenziswa ngokuthe ngqo njengabalawuli bokusebenza kweplatelet kunye ne-thrombosis.Okona kubaluleke kakhulu, uninzi lwezi zinto zinomsebenzi wokuguqula iiseli zomzimba.I-Platelet ADP ibonwa yi-P2Y12ADP receptor kwiiseli ze-dendritic (DC), ngaloo ndlela inyusa i-antigen endocytosis.I-DC (i-antigen ebonisa iseli) ibaluleke kakhulu ekuqaliseni i-T cell immune response kunye nokulawula impendulo ekhuselayo yokuzivikela, edibanisa inkqubo ye-innate immune system kunye ne-adaptive immune system.Ukongezelela, i-platelet adenosine triphosphate (ATP) ithumela izibonakaliso nge-T cell receptor P2X7, ekhokelela ekunyuseni ukuhlukana kweeseli ze-CD4 T ezincedisayo kwiiseli ze-proinflammatory T ze-17 (Th17).Ezinye iiplatelet ezixineneyo zegranule (ezifana ne-glutamate kunye ne-serotonin) zibangela ukufuduka kweeseli ze-T kunye nokwandisa ukwahlula kwe-monocyte kwi-DC, ngokulandelanayo.Kwi-PRP, la ma-immunomodulators aphuma kumasuntswana axineneyo atyetyiswe kakhulu kwaye anemisebenzi emininzi yokuzikhusela.
Inani lokusebenzisana ngokuthe ngqo kunye nokungathanga ngqo phakathi kweeplatelet kunye nezinye (i-receptor) iiseli zibanzi.Ngoko ke, ukusetyenziswa kwe-PRP kwindawo yendawo ye-pathological tissue kunokubangela iintlobo ezahlukeneyo zokuvuvukala.
Ugxininiso lwePlatelet
I-C-PRP kufuneka iqulethe iidosi zeklinikhi zeeplatelet ezigxininisiweyo ukuvelisa iziphumo zonyango ezinoncedo.Iiplatelets kwi-C-PRP kufuneka zikhuthaze ukwanda kweeseli, ukuhlanganiswa kwezinto ze-mesenchymal kunye neurotrophic, ukukhuthaza ukufuduka kweeseli ze-chemotactic kunye nokuvuselela umsebenzi we-immunoregulatory, njengoko kuboniswe kumfanekiso.
Iiplatelets ezisebenzayo, ukukhululwa kwe-PGF kunye ne-adhesion molecules zidibanisa iintlobo ezahlukeneyo zokusebenzisana kweeseli: i-chemotaxis, i-cell adhesion, i-migration, kunye nokwahlukana kweeseli, kunye nokulawula imisebenzi yokulawula i-immune.Ezi ntsebenziswano zeplatelet cell-cell zinegalelo kwi-angiogenesis kunye nomsebenzi wokuvuvukala, kwaye ekugqibeleni zivuselela inkqubo yokulungisa izicubu.Izifinyezo: i-BMA: i-bone marrow aspirate, i-EPC: iiseli ze-endothelial progenitor, i-EC: iiseli ze-endothelial, i-5-HT: i-5-hydroxytryptamine, i-RANTES: umgaqo osebenzayo we-T cell expression kunye ne-putive secretion, i-JAM: i-junction adhesion molecule, i-CD40L: iqoqo I-40 ligand, i-SDF-1 α: i-Stromal cell-derived factor-1 α, i-CXCL: i-chemokine (i-CXC motif) i-ligand, i-PF4: i-platelet factor 4. Ithathwe kwi-Everts et al.
UMarx wayengumntu wokuqala ukubonisa ukuba ukuphulukiswa kwethambo kunye nezicubu ezithambileyo kwaphuculwa, kwaye inani elincinci leplatelet laliyi-1 × 10 6 /µL. Ezi ziphumo zaqinisekiswa kuphononongo lwe-lumbar fusion ngokusebenzisa i-intervertebral foramen, xa idosi yeplatelet yayinkulu kunoko. 1.3 × Kwi-106 platelets/µ L, olu phononongo lubonise ukudibanisa ngakumbi.Ukongeza, uGiusti et al.Kutyhilwa i-1.5 × Indlela yokulungisa izicubu kwi-dose ye-109 idinga iiplatelet / mL ukukhupha i-angiogenesis esebenzayo ngokusebenzisa umsebenzi weseli endothelial.Kuphononongo lwamva nje, ugxininiso oluphezulu lwehlise amandla e-angiogenesis yeeplatelet ngaphakathi najikelele kwiifollicles.Ukongezelela, idatha yangaphambili ibonise ukuba i-dose ye-PRP iya kuchaphazela iziphumo zonyango.Ngoko ke, ukwenzela ukuba kubangele kakhulu ukusabela kwe-angiogenesis kunye nokukhuthaza ukwanda kweeseli kunye nokufuduka kweeseli, i-C-PRP kufuneka iqulethe ubuncinane i-7.5 kwibhotile yonyango ye-5-mL ye-PRP × 10 9 inokuhambisa iiplatelet.
Ukongeza kukuxhomekeka kwethamo, umphumo we-PRP kumsebenzi weseli ubonakala uxhomekeke kakhulu kwixesha.USophie et al.Ezi ziphumo zibonisa ukuba ukubonakaliswa kwexesha elifutshane kwi-lysates yeplatelet yomntu kunokuvuselela ukwanda kweeseli zethambo kunye ne-chemotaxis.Ngokuchasene noko, ukubonakaliswa kwexesha elide kwi-PRP kuya kukhokelela kumanqanaba aphantsi e-alkaline phosphatase kunye nokubunjwa kwamaminerali.
Iseli ebomvu yegazi
Iiseli ezibomvu zegazi zinoxanduva lokuhambisa ioksijini kwizicubu kunye nokuhambisa icarbon dioxide ukusuka kwizicubu ukuya emiphungeni.Azinayo i-nucleus kwaye zenziwe ngeemolekyuli ze-heme ezibophelela kwiiprotheni.Isinyithi kunye neenxalenye zeheme kwiiseli ezibomvu zegazi zikhuthaza ukudibanisa ioksijini kunye nekharbon diokside.Ngokuqhelekileyo, umjikelo wobomi beeseli ezibomvu zegazi umalunga neentsuku ezili-120.Ziyasuswa kujikelezo yi macrophage ngenkqubo ebizwa RBC ukuguga.Iiseli ezibomvu zegazi kwiisampuli ze-PRP zingonakaliswa phantsi kweemeko ze-shear (umzekelo, utyando lwegazi elipheleleyo, inkqubo ye-immune-mediated, uxinzelelo lwe-oxidative okanye isikimu sokugxininiswa kwe-PRP enganeleyo).Ngoko ke, i-RBC cell membrane iyabola kwaye ikhuphe i-hemoglobin enetyhefu (Hb), ilinganiswa nge-plasma ye-hemoglobin yamahhala (PFH), i-heme kunye nentsimbi.].I-PFH kunye neemveliso zayo zokuthotywa (i-heme kunye nentsimbi) ngokudibeneyo zikhokelela kwimiphumo eyingozi kunye ne-cytotoxic kwizicubu, ezikhokelela kuxinzelelo lwe-oxidative, ukulahlekelwa kwe-nitric oxide, ukusetyenziswa kweendlela ezivuthayo kunye nokunyanzeliswa kwe-immunosuppression.Ezi ziphumo ekugqibeleni ziya kubangela ukungasebenzi kakuhle kwe-microcirculation, i-vasoconstriction yendawo kunye nokulimala kwe-vascular, kunye nomonakalo omkhulu wezicubu.
Into ebaluleke kakhulu kukuba xa i-RBC equkethe i-C-PRP ihanjiswa kwizicubu, iya kubangela ukusabela kwendawo ebizwa ngokuba yi-eryptosis, eya kubangela ukukhululwa kwe-cytokine esebenzayo kunye ne-macrophage migration inhibitor.Le cytokine inqanda ukufuduka kwe-monocytes kunye ne-macrophages.Isebenzisa imiqondiso eyomeleleyo ye-pro-inflammatory kwizicubu ezijikelezileyo, inqanda ukufuduka kweeseli ze-stem kunye nokwanda kwe-fibroblast, kwaye ikhokelela kukungasebenzi kakuhle kweeseli zendawo.Ngoko ke, kubalulekile ukunciphisa ukungcola kwe-RBC kumalungiselelo e-PRP.Ukongezelela, indima yeeseli ezibomvu zegazi ekuvuseleleni izicubu azizange zimiselwe.I-C-PRP eyaneleyo ye-centrifugation kunye nenkqubo yokulungiselela ngokuqhelekileyo iya kunciphisa okanye ikhuphe ubukho beeseli ezibomvu zegazi, ngaloo ndlela igweme imiphumo emibi ye-hemolysis kunye ne-polycythemia.
I-Leukocytes kwi-C-PRP
Ubukho beeseli ezimhlophe zegazi kumalungiselelo e-PRP kuxhomekeke kwisixhobo sonyango kunye neskimu sokulungiselela.Kwizixhobo ze-PRP ezisekelwe kwi-plasma, iiseli ezimhlophe zegazi zipheliswe ngokupheleleyo;Nangona kunjalo, iiseli zegazi ezimhlophe zazigxininiswe kakhulu kulungiselelo lwe-PRP lwe-erythrocyte sedimentation brown layer.Ngenxa yeendlela zayo zokuzikhusela kwi-immune kunye ne-host, iiseli ezimhlophe zegazi zichaphazela kakhulu i-biology yangaphakathi yeemeko ezibukhali kunye nezingapheliyo.Ezi mpawu ziya kuxoxwa ngakumbi ngezantsi.Ngoko ke, ubukho bee-leukocyte ezithile kwi-C-PRP kunokubangela imiphumo ebalulekileyo yeselula kunye nezicubu.Ngokukodwa ngakumbi, iinkqubo ezahlukeneyo ze-PRP erythrocyte sedimentation brown-yellow layer layers zisebenzisa izikimu zamalungiselelo ahlukeneyo, ngaloo ndlela zivelisa umlinganiselo ohlukeneyo we-neutrophils, lymphocytes kunye ne-monocytes kwi-PRP.I-Eosinophils kunye ne-basophils ayinakulinganiswa kumalungiselelo e-PRP ngenxa yokuba i-membrane zabo zeeseli zibuthathaka kakhulu ukuba zingamelana namandla okucubungula i-centrifugal.
Iineutrophils
Iineutrophils zibalulekile leukocyte kwiindlela ezininzi zokuphilisa.Ezi ndlela zidibanisa kunye neeprotheyini ze-antimicrobial ezikhoyo kwiiplatelet ukwenza umqobo oshinyeneyo ngokuchasene neentsholongwane ezihlaselayo.Ubukho be-neutrophils bunqunywe ngokwenjongo yonyango ye-C-PRP.Ukunyuka kwamanqanaba okuvuvukala kwezicubu kunokufuneka kukhathalelo olungapheliyo lwe-PRP biotherapy okanye kwizicelo ezijoliswe ekukhuleni kwamathambo okanye ukuphilisa.Okubalulekileyo, imisebenzi eyongezelelweyo ye-neutrophil ifunyenwe kwiimodeli ezininzi, igxininisa indima yabo kwi-angiogenesis kunye nokulungiswa kwezicubu.Nangona kunjalo, i-neutrophils inokubangela iziphumo ezinobungozi, ngoko ke azifanelekanga kwezinye izicelo.UZhou noWang babonise ukuba ukusetyenziswa kwe-PRP ecebileyo kwi-neutrophils kunokukhokelela ekwandeni komlinganiselo wohlobo lwe-III i-collagen ukuthayipha i-collagen ye-I, ngaloo ndlela ikhulisa i-fibrosis kunye nokunciphisa amandla e-tendon.Ezinye iimpawu ezinobungozi ezixutywe yi-neutrophils kukukhululwa kwe-cytokines evuthayo kunye ne-matrix metalloproteinases (MMPs), enokukhuthaza ukuvuvukala kunye ne-catabolism xa isetyenziswe kwizicubu.
Leukomonocyte
Kwi-C-PRP, i-lymphocyte ye-T kunye ne-B ye-mononuclear igxininiswe ngakumbi kunanoma yiyiphi enye iiseli zegazi ezimhlophe.Zinxulumene ngokusondeleyo ne-cell-mediated cytotoxic adaptive immunity.Iilymphocyte zinokubangela ukusabela kweeseli ukulwa nosulelo kwaye ziqhelane nabahlaseli.Ukongezelela, i-T-lymphocyte evela kwi-cytokines (i-interferon- γ [IFN- γ] kunye ne-interleukin-4 (IL-4) iphucula i-polarization ye-macrophages. Verassar et al. Kungqinwe ukuba i-lymphocyte ye-T eqhelekileyo inokukhuthaza ngokungathanga ngqo ukuphiliswa kwezicubu kwi-macrophages. imodeli yempuku ngokulawula ukwahlulwa kwe-monocytes kunye ne-macrophages.
I-Monocyte - iseli yokulungisa izinto ezininzi
Ngokutsho kwesixhobo sokulungiselela i-PRP esisetyenzisiweyo, i-monocytes inokugqithisa okanye ingabikho kwibhotile yonyango ye-PRP.Ngelishwa, ukusebenza kwabo kunye nokukwazi kwabo ukuvuselela akufane kuxoxwe kwiincwadi.Ngoko ke, ingqalelo encinci ihlawulwa kwi-monocytes kwindlela yokulungiselela okanye ifomula yokugqibela.Iqela le-Monocyte liyi-heterogeneous, livela kwiiseli ze-progenitor kumongo wethambo, kwaye zithuthelwa kwizicubu ze-peripheral ngokusebenzisa i-hematopoietic stem cell pathway ngokwe-microenvironment stimulation.Ngexesha le-homeostasis kunye nokuvuvukala, i-monocytes ejikelezayo ishiya umsinga wegazi kwaye igaywe kwizicubu ezonzakeleyo okanye ezonakalisiwe.Ziyakwazi ukusebenza njenge-macrophages (M Φ) Iiseli ze-Effector okanye iiseli ze-progenitor.I-Monocytes, i-macrophages kunye neeseli ze-dendritic zibonisa inkqubo ye-phagocytic ye-mononuclear (MPS) .Kwizicubu ezonakeleyo, i-macrophages ehlala kuyo, izinto ezikhula kwindawo, i-cytokines e-pro-inflammatory, iiseli ze-apoptotic okanye ze-necrotic kunye neemveliso ze-microbial ziqala i-monocytes ukuhlula kumaqela eeseli ze-MPS.Masithi xa i-C-PRP iqulethe i-monocyte ephezulu yesivuno ifakwe kwi-microenvironment yendawo yesifo, i-monocytes inokuthi ihluke kwi-M Φ Ukwenza utshintsho olukhulu lweeseli.
Ukusuka kwi-monocyte ukuya kwi-M Φ Kwinkqubo yokuguqulwa, i-M Φ Phenotype ethile.Kwiminyaka elishumi edlulileyo, imodeli iye yaphuhliswa, edibanisa i-M Φ Inkqubo eyinkimbinkimbi yokusebenza ichazwa njenge-polarization yamazwe amabini aphikisanayo: M Φ Phenotype 1 (M Φ 1, i-Classic activation) kunye ne-M Φ Phenotype 2 (M Φ 2, enye indlela yokuvula).I-M Φ 1 ibonakaliswe ngokutshatyalaliswa kwe-cytokine secretion (IFN- γ) kunye ne-nitric oxide ukuvelisa indlela esebenzayo yokubulala i-pathogen.M Φ I-phenotype iphinda ivelise i-vascular endothelial growth factor (VEGF) kunye ne-fibroblast factor factor (FGF).M Φ I-phenotype yenziwe ngamaseli achasene nokuvuvukala kunye ne-phagocytosis ephezulu.M Φ 2 Ukuvelisa amacandelo e-matrix e-extracellular, i-angiogenesis kunye ne-chemokines, kunye ne-interleukin 10 (IL-10).Ukongeza kwi-pathogen yokukhusela, i-M Φ inokunciphisa ukuvuvukala nokukhuthaza ukulungiswa kwezicubu.Kuyaphawuleka ukuba i-M Φ 2 iye yahlulelwa kwi-M in vitro Φ 2a, M Φ 2b kunye ne-M Φ 2. Kuxhomekeke kwi-stimulus.Kwi-vivo ukuguqulelwa kwezi subtypes kunzima kuba izicubu zinokuqulatha umxube we-M Φ Amaqela.Kuyathakazelisa, ngokusekelwe kwimiqondiso yendawo yendawo kunye namanqanaba e-IL-4, i-proinflammatory M Φ 1 inokuguqulwa ukuze ikhuthaze ukulungiswa kwe-M Φ 2. Ukusuka kule datha, kunengqiqo ukucinga ukuba kukho ukugxilwa okuphezulu kwe-monocytes kunye ne-M Φ C-PRP amalungiselelo. inokuba negalelo ekulungisweni kwezicubu ezingcono kuba zinokulungiswa kwezicubu ezichasayo kunye nesakhono sokuhambisa umqondiso weseli.
Inkcazo edidayo yeqhekeza legazi elimhlophe kwi-PRP
Ubukho beeseli ezimhlophe zegazi kwiibhotile zonyango ze-PRP kuxhomekeke kwisixhobo sokulungiselela i-PRP kwaye kunokuba nentlukwano ebalulekileyo.Kukho iingxabano ezininzi malunga nobukho be-leukocytes kunye negalelo labo kwiimveliso ezahlukeneyo ze-PRP (ezifana ne-PRGF, i-P-PRP, i-LP-PRP, i-LR-PRP, i-P-PRF kunye ne-L-PRF) Kuphononongo lwamva nje, ezintandathu izilingo ezilawulwayo (inqanaba lobungqina be-1) kunye nezifundo ezintathu ezilindelekileyo zokuthelekisa (inqanaba lobungqina be-2) libandakanya izigulane ze-1055, ezibonisa ukuba i-LR-PRP kunye ne-LP-PRP inokhuseleko olufanayo.Umbhali waphetha ukuba ukusabela okungathandekiyo kwe-PRP akunakunxulumana ngokuthe ngqo nokuxinana kweeseli ezimhlophe zegazi.Kwesinye isifundo, i-LR-PRP ayizange itshintshe i-interleukin evuthayo (IL-1) kwi-OA idolo β, IL-6, IL-8 kunye ne-IL-17).Ezi ziphumo zixhasa imbono yokuba indima ye-leukocytes kumsebenzi we-biological we-PRP kwi-vivo inokuvela kwi-crosstalk phakathi kweeplatelet kunye ne-leukocytes.Oku kusebenzisana kunokukhuthaza i-biosynthesis yezinye izinto (ezifana ne-lipoxygen), ezinokuthi zikhuphe okanye zikhuthaze ukuhla kokuvuvukala.Emva kokukhululwa kokuqala kweeamolekyu ezivuthayo (i-arachidonic acid, i-leukotriene kunye ne-prostaglandin), i-lipoxygen A4 ikhutshwa kwiiplatelets ezisebenzayo ukukhusela i-neutrophil activation.Kulo mmandla apho i-M Φ Phenotype ukusuka ku-M Φ 1 Tshintshela kwi-M Φ 2. Ukongezelela, kukho ubungqina obuninzi bokuthi ukujikeleza iiseli ze-mononuclear ziyakwazi ukuhlukana kwiindidi ze-non-phagocytic cell cell ngenxa yobuninzi babo.
Uhlobo lwe-PRP luya kuchaphazela inkcubeko ye-MSC.Xa kuthelekiswa ne-PRP ecocekileyo okanye iisampulu ze-PPP, i-LR-PRP inokubangela ukwanda okuphezulu komongo we-MSCs (BMMSCs), kunye nokukhululwa ngokukhawuleza kunye nokusebenza okungcono kwe-PGF yezinto eziphilayo.Zonke ezi mpawu zilungele ukongeza i-monocytes kwibhotile yonyango ye-PRP kunye nokuqaphela amandla abo okuzivikela kunye nokwahlulahlula.
I-Congenital kunye ne-adaptive immune regulation ye-PRP
Owona msebenzi udumileyo we-physiological of platelets kukulawula ukopha.Ziqokelela kwindawo yomonakalo wezicubu kunye nemithambo yegazi eyonakalisiweyo.Ezi ziganeko zibangelwa ukubonakaliswa kwee-interins kunye ne-selectins ezikhuthaza ukunamathela kweplatelet kunye nokudibanisa.I-endothelium eyonakalisiweyo iqhubela phambili ngakumbi le nkqubo, kwaye i-collagen evezwayo kunye nezinye iiprotheni ze-matrix ze-subendothelial zikhuthaza ukusebenza okunzulu kweeplatelet.Kule meko, indima ebalulekileyo yentsebenziswano phakathi kwe-von Willebrand factor (vWF) kunye ne-glycoprotein (GP), ngakumbi i-GP-Ib, ibonakaliswe.Emva kokusebenza kweplatelet, i-platelet α-, iDense, i-lysosome kunye ne-T-granules zilawula i-exocytosis kwaye zikhulule imixholo yazo kwindawo ye-extracellular.
Imolekyuli yokubambelela kwiplatelet
Ukuze siqonde kakuhle indima ye-PRP kwii-tissue ezivuthayo kunye neeplatelet kwiimpendulo ze-immune, kufuneka siqonde indlela eyahlukileyo i-platelet surface receptors (i-integrins) kunye ne-junction adhesion molecules (JAM) kunye nokusebenzisana kweeseli kunokuqalisa iinkqubo ezibalulekileyo kwi-innate and adaptive immunity.
Ii-Integrins ziimolekyuli zokubambelela kumphezulu weeseli ezifumaneka kwiindidi ezahlukeneyo zeeseli kwaye zibonakaliswa ngobuninzi kwiiplatelet.Ii-Integrins ziquka i-a5b1, i-a6b1, i-a2b1 LFA-2, (GPIa / IIa) kunye ne-aIIbb3 (GPIIb / IIIa).Ngokuqhelekileyo, zibakho kwimeko emileyo kunye nephantsi yobudlelwane.Emva kokusebenza, batshintshela kwimeko yobudlelwane obubophezelayo obuphezulu be-ligand.I-Integrins inemisebenzi eyahlukeneyo kwiiplatelet kwaye ithatha inxaxheba ekusebenzisaneni kweeplatelet ezineentlobo ezininzi zeeseli ezimhlophe zegazi, iiseli ze-endothelial kunye ne-matrix engaphandle.Ukongezelela, i-GP-Ib-V-IX i-complex ibonakaliswe kwi-membrane yeplatelet kwaye iyona receptor ephambili yokubopha nge-von vWF.Olu nxibelelwano ludibanisa unxibelelwano lokuqala phakathi kweeplatelet kunye nezakhiwo eziveziweyo ze-subendothelial.I-Platelet integrin kunye ne-GP complex zihambelana neenkqubo ezahlukeneyo zokuvuvukala kwaye zidlala indima ebalulekileyo ekubunjweni kwe-platelet-leukocyte complex.Ngokukodwa, i-integrin aIIbb3 iyimfuneko ukwenza i-complex ezinzile ngokudibanisa i-fibrinogen kunye ne-macrophage 1 antigen (Mac-1) i-receptor kwi-neutrophils.
Iiplatelets, i-neutrophils kunye neeseli ze-vascular endothelial zivakalisa iimolekyuli ezithile zokubambelela kweeseli, ezibizwa ngokuba yi-selectin.Ngaphantsi kweemeko ezivuthayo, iiplatelet zivakalisa i-P-selectin kunye neutrophil L-selectin.Emva kokusebenza kweplatelet, i-P-selectin inokubophelela kwi-ligand PSGL-1 ekhoyo kwi-neutrophils kunye ne-monocytes.Ukongezelela, ukubopha kwe-PSGL-1 kuqalisa i-intracellular signal cascade reaction, eyenza i-neutrophils nge-neutrophil integrin Mac-1 kunye ne-lymphocyte ehlobene nomsebenzi we-antigen 1 (LFA-1).I-Mac-1 esebenzayo ibophelela kwi-GPIb okanye i-GPIIb/IIIa kwiiplatelets ngokusebenzisa i-fibrinogen, ngaloo ndlela izinzile intsebenziswano phakathi kwe-neutrophils kunye neeplatelet.Ukongeza, i-LFA-1 esebenzayo inokudibanisa ne-platelet intercellular adhesion molecule 2 ukuqhubela phambili ukuzinzisa i-neutrophil-platelet complex ukukhuthaza ukunamathela kwexesha elide kunye neeseli.
IiPlatelets kunye ne-leukocyte zidlala indima ephambili kwiimpendulo ze-immune zangaphakathi kunye neziguquguqukayo
Umzimba unokwazi ukubona imizimba yangaphandle kunye nezicubu ezonzakeleyo kwizifo ezibukhali okanye ezingapheliyo ukuqalisa ukuphiliswa kwenxeba lokusabela kunye nendlela yokuvuvukala.Amajoni omzimba azelwe kwaye alungelelanisiweyo akhusela umkhosi kusulelo, kwaye iiseli ezimhlophe zegazi zidlala indima ebalulekileyo ekugqitheni phakathi kwezi zimbini iinkqubo.Ngokukodwa, i-monocytes, i-macrophages, i-neutrophils kunye neeseli ezibulalayo zendalo zidlala indima ebalulekileyo kwinkqubo yokuzalwa, ngelixa i-lymphocytes kunye ne-subsets yazo idlala indima efanayo kwi-immune system.
Ukusebenzisana kwePlatelet kunye ne-leukocyte kwintsebenziswano ye-innate immune cell.I-Platelet isebenzisana ne-neutrophils kunye ne-monocytes, kwaye ekugqibeleni kunye ne-M Φ Ukusebenzisana, ukulungelelanisa nokwandisa imisebenzi yabo ye-effector.Olu nxibelelwano lweplatelet-leukocyte lukhokelela ekudumbeni ngeendlela ezahlukeneyo, kubandakanya iNETosis.Izifinyezo: i-MPO: i-myeloperoxidase, i-ROS: iintlobo ze-oksijini ezisebenzayo, i-TF: i-tissue factor, i-NET: i-neutrophil extracellular trap, NF- κ B: I-Nuclear factor kappa B, M Φ: Macrophages.
Amajoni omzimba azalwa nawo
Indima yesistim somzimba esizalwa naso kukuchonga into engacacanga ii-microorganisms ezihlaselayo okanye amaqhekeza ezicubu kunye nokukhuthaza ukukhutshwa kwazo.Xa izakhiwo ezithile zeemolekyuli ezibizwa ngokuba yi-surface expression pattern recognition receptors (PRRs) zidibanisa neepatheni zemolekyuli ezinxulumene ne-pathogen kunye neepatheni zemolekyuli ezinxulumene nomonakalo, inkqubo yokuzikhusela engaphakathi iya kwenziwa isebenze.Kukho iintlobo ezininzi ze-PRRs, kuquka i-Toll-like receptor (TLR) kunye ne-RIG-1 njenge-receptor (RLR).La ma-receptors angenza i-transcription factor i-kappa B (NF- κ B) iphinde ilawule iinkalo ezininzi ze-innate and adaptive immune response.Kuyathakazelisa ukuba iiplatelet nazo zivakalisa iindidi ze-immunoregulatory receptor molecules ebusweni babo kunye ne-cytoplasm, njenge-P-selectin, i-protein ye-transmembrane CD40 ligand (CD40L), i-cytokines (njenge-IL-1 β, TGF- β) kunye ne-platelet-specific TLR. Ngoko ke, iiplatelets zinokusebenzisana neeseli ezahlukeneyo zokuzikhusela kwizifo.
Ukusebenzisana kweplatelet-white cell kwi-innate immunity
Xa iiplatelet zingena okanye zihlasela ukuhamba kwegazi okanye izicubu, iiplatelet enye yeeseli ezibona ukulimala kwe-endothelial kunye ne-microbial pathogens kuqala.I-Platelet aggregation kunye nokukhuthaza ukukhululwa kwee-agonists ze-platelet ADP, i-thrombin kunye ne-vWF, okubangelwa ukusebenza kweplatelet kunye nokubonakaliswa kwe-platelet chemokine receptors C, i-CC, i-CXC kunye ne-CX3C, ngaloo ndlela ibangela iiplatelet kwindawo enesifo okanye ukulimala.
Umxokomezelo wemvelo wokuzikhusela kwizifo umiselwa kwangaphambili ngokwemfuza ukuze kubonwe abahlaseli, njengeentsholongwane, iibhaktheriya, izifunxi-gazi kunye neetyhefu, okanye amanxeba ezicwili namanxeba.Yinkqubo engeyiyo ngqo, kuba nayiphi na i-pathogen iya kuchongwa njengeyangaphandle okanye engeyiyo kwaye ifumaneke ngokukhawuleza.Isistim somzimba sokuzivikela sixhomekeke kwiseti yeeprotheyini kunye ne-phagocytes, eziqaphela iimpawu ezigcinwe kakuhle ze-pathogens kwaye zisebenze ngokukhawuleza impendulo yokuzivikela ekuncedeni ukuphelisa abahlaseli, nokuba ngaba umkhosi awuzange uvelele kwiintsholongwane ezithile ngaphambili.
I-neutrophils, i-monocytes kunye neeseli ze-dendritic zezona ziqhelekileyo iiseli ze-immune zangaphakathi egazini.Ukuqeshwa kwabo kuyimfuneko kwimpendulo eyaneleyo yokuzikhusela kwangethuba.Xa i-PRP isetyenziselwa unyango lokuvuselela, ukusebenzisana kwe-platelet-white cell kulawula ukuvuvukala, ukuphulukiswa kwesilonda kunye nokulungiswa kwezicubu.I-TLR-4 kwiiplatelet ivuselela ukusebenzisana kweplatelet-neutrophil, elawula into ebizwa ngokuba yi-leukocyte oxidative burst ngokulawula ukukhululwa kweentlobo ze-oksijini ezisebenzayo (ROS) kunye ne-myeloperoxidase (MPO) kwi-neutrophils.Ukongezelela, ukusebenzisana phakathi kweplatelet-neutrophil kunye ne-neutrophil degranulation kukhokelela ekubunjweni kwe-neutrophil-extracellular traps (NETs).I-NETs zenziwe nge-nucleus ye-neutrophil kunye nezinye iziqulatho ze-neutrophil ze-intracellular, ezinokubamba iibhaktheriya kwaye zibabulale nge-NETosis.Ukwenziwa kwee-NETs yindlela ebalulekileyo yokubulala i-neutrophils.
Emva kokusebenza kweplatelet, i-monocytes inokufudukela kwizicubu ezigulayo kunye ne-degenerative, apho zenza imisebenzi yokubambelela kwaye zikhuphe iimolekyuli ezivuthayo ezinokutshintsha i-chemotaxis kunye neproteolytic properties.Ukongezelela, iiplatelet zingenza i-monocyte i-NF- κ B isebenze ukulawula umsebenzi we-effector we-monocytes, umlamli oyintloko wempendulo yokuvuvukala kunye nokusebenza kunye nokuhlukana kweeseli zomzimba.IiPlatelets ziqhubela phambili ukukhuthaza i-endogenous oxidative burst of monocytes ukukhuthaza ukutshatyalaliswa kwe-phagocytic pathogens.Ukukhutshwa kwe-MPO kuxutyushwa ngokusebenzisana ngokuthe ngqo phakathi kweplatelet-monocyte CD40L-MAC-1.Kuyathakazelisa ukuba xa i-P-selectin ivuselela iiplatelet phantsi kweemeko zezicubu ezivuthayo kunye nezingapheliyo, i-chemokines ephuma kwiplatelet PF4, i-RANTES, i-IL-1 β kunye ne-CXCL-12 inokuthintela i-apoptosis ezenzekelayo ye-monocytes, kodwa ikhuthaze ukuhlukana kwabo kwi-macrophages.
Isistim somzimba esilungelelanisiweyo
Emva kokuba isistim somzimba somzimba esingachanekanga sibona umonakalo wentsholongwane okanye wezicubu, amajoni omzimba athile aya kuthatha indawo.Iinkqubo eziguqukayo ziquka i-antigen-binding B lymphocytes (iiseli ze-B) kunye ne-T lymphocytes eziqhelekileyo (i-Treg) ezilungelelanisa ukucocwa kweentsholongwane.Iiseli ze-T zinokwahlulwa ngokweeseli ezincedisayo (iiseli ze-T) kunye neeseli ze-T ze-cytotoxic (iiseli ze-Tc, ezikwabizwa ngokuba zii-T killer cells).Iiseli ze-T ziphinde zahlulwe zibe yi-Th1, i-Th2 kunye neeseli ze-Th17, ezinemisebenzi ephambili ekudumbeni.Iiseli zinokukhupha i-proinflammatory cytokines (umz. IFN- γ, TNF- β) kunye ne-interleukins ezininzi (umzekelo, i-IL-17) Zisebenza ngokukodwa ekukhuseleni i-intracellular virus kunye nosulelo lwebhaktheriya. Iiseli ze-Tc ziiseli ezisebenzayo, ezinokuthi ziphelise i-intracellular kunye ne-extracellular microorganisms kunye neeseli.
Kuyathakazelisa ukuba iiseli ze-Th2 zivelisa i-IL-4 kwaye zichaphazela i-M Φ Polarization, M Φ Ukuvuselelwa okukhokelwayo M Φ 2 Phenotype, ngelixa i-IFN- γ M Φ Ukutshintsha kwi-inflammatory M Φ 1 Phenotype, exhomekeke kwidosi kunye nexesha le-cytokines.Emva kokuba i-IL-4 isebenze, i-M Φ 2 yenza iiseli ze-Treg ukuba zihluke kwiiseli ze-Th2, kwaye emva koko zivelise i-IL-4 eyongezelelweyo (i-loop feedback loop).Iiseli ze-T ziguqula i-M Φ I-phenotype iqondiswe kwi-phenotype yokuvuselela ngokuphendula kwii-biological agents zemvelaphi yezicubu.Le ndlela isekelwe kubungqina bokuba iiseli ze-T zidlala indima ebalulekileyo ekulawuleni ukuvuvukala kunye nokulungiswa kwezicubu.
Ukusebenzisana kweplatelet-white cell kwi-adaptive immunity
Isixokelelwano somzimba esiguqukayo sisebenzisa i-antigen-specific receptors kwaye sikhumbula iipathogens ebezidibene nazo ngaphambili, kwaye zizitshabalalise xa zidibana nomkhosi.Nangona kunjalo, ezi mpendulo ze-immune eziguqukayo zakhula kancinci.UKonias et al.Ibonisa ukuba inxalenye yeplatelet inegalelo ekuboneni umngcipheko kunye nokulungiswa kwezicubu, kunye nokuba ukusebenzisana phakathi kweeplatelet kunye ne-leukocytes kukhuthaza ukusebenza kwempendulo ye-immune eguquguqukayo.
Ngexesha lokuphendula kwe-immune eguquguqukayo, iiplatelet zikhuthaza iimpendulo ze-monocyte kunye ne-macrophage ngokusebenzisa i-DC kunye ne-NK ye-cell maturation, ekhokelela kwi-cell T kunye neempendulo zeseli ze-B.Ke ngoko, amacandelo egranule yeplatelet achaphazela ngokuthe ngqo ukhuselo lomzimba ngokuchaza i-CD40L, imolekyuli eyimfuneko ekulawuleni impendulo eguquguqukayo yamajoni omzimba.IiPlatelets nge-CD40L azidlali kuphela indima kwi-antigen presentation, kodwa zikwachaphazela ukusabela kweeseli ze-T.ULiu et al.Kwafunyaniswa ukuba iiplatelet zilawula impendulo yeseli ye-CD4 T ngendlela entsonkothileyo.Lo mmiselo ohlukeneyo we-CD4 T cell subsets uthetha ukuba iiplatelet zikhuthaza iiseli ze-CD4 T ukuba ziphendule kwi-inflammation stimuli, ngaloo ndlela zivelise iimpendulo ezinamandla ezixhasayo kunye nezichasayo.
IiPlatelets zikwalawula impendulo ye-B cell-mediated adaptive to microbial pathogens.Kuyaziwa ukuba i-CD40L kwiiseli ze-CD4 T ezisebenzayo ziya kubangela i-CD40 yeeseli ze-B, ukubonelela ngesibonakaliso sesibini esifunekayo kwi-T-cell-dependent B lymphocyte activation, ukuguqulwa okulandelayo kwe-allotype, kunye nokwahlukana kweeseli ze-B kunye nokwanda.Ngokubanzi, iziphumo zibonisa ngokucacileyo imisebenzi eyahlukeneyo yeeplatelet kwi-immunity eguquguqukayo, ebonisa ukuba iiplatelet zidibanisa ukusebenzisana phakathi kweeseli ze-T kunye neeseli ze-B nge-CD40-CD40L, ngaloo ndlela ziphucula impendulo ye-cell exhomekeke kwi-T-cell.Ukongezelela, iiplatelets zizityebi kwi-cell surface receptors, ezinokukhuthaza ukusebenza kweplatelet kunye nokukhulula inani elikhulu leemolekyuli ezivuthayo kunye ne-biological esebenzayo egcinwe kwiintlobo zeplatelet ezahlukeneyo, ngaloo ndlela zichaphazela impendulo ye-immune ye-innate kunye ne-adaptive.
Indima eyandisiweyo ye-serotonin ephuma kwiplatelet kwi-PRP
I-Serotonin (i-5-hydroxytryptamine, i-5-HT) inendima ecacileyo ecacileyo kwinkqubo ye-nervous central (CNS), kuquka ukunyamezela intlungu.Kuqikelelwa ukuba ininzi ye-5-HT yomntu iveliswa kwi-gastrointestinal tract kwaye emva koko ngokujikeleza kwegazi, apho ixutywe ngamaplatelet ngokusebenzisa i-serotonin reuptake transporter kwaye igcinwe kwiincinci ezixineneyo kwi-concentration ephezulu (65 mmol / L).I-5-HT i-neurotransmitter eyaziwayo kunye ne-hormone enceda ukulawula iinkqubo ezahlukeneyo ze-neuropsychological kwi-CNS (ephakathi kwe-5-HT).Nangona kunjalo, ininzi ye-5-HT ikhona ngaphandle kwe-CNS (i-peripheral 5-HT), kwaye ibandakanyeka ekulawuleni imisebenzi ye-biological systemic kunye ne-cellular biological systems ye-multiple organ systems, kubandakanywa ne-cardiovascular, lung, gastrointestinal, urogenital kunye ne-platelet functional systems.I-5-HT ine-metabolism exhomekeke kugxininiso kwiindidi zeentlobo zeeseli, kubandakanywa i-adipocytes, iiseli ze-epithelial kunye neeseli ezimhlophe zegazi.I-Peripheral 5-HT iphinde ibe yimodyuli enamandla yokuzivikela, enokuthi ivuselele okanye ivimbele ukuvuvukala kwaye ichaphazele iiseli ezahlukeneyo ze-immune ngokusebenzisa i-5-HT receptor (5HTR).
IParacrine kunye ne-autocrine mechanism yeHT
Umsebenzi we-5-HT ulungelelaniswe ngokubambisana kwayo kunye ne-5HTRs, eyona nto i-superfamily enamalungu asixhenxe (5-HT 1 - 7) kwaye ubuncinane i-14 eyahlukeneyo ye-receptor subtypes, kubandakanywa ilungu elisanda kufunyanwa 5-HT 7, i-peripheral yayo kunye umsebenzi wokulawula intlungu.Kwinkqubo ye-platelet degranulation, iiplatelet ezisebenzayo zifihla inani elikhulu le-platelet-derived 5-HT, enokukhuthaza ukuchithwa kwe-vascular kunye nokukhuthaza ukusebenza kweeplatelet ezikufutshane kunye ne-lymphocytes ngokubonakaliswa kwe-5-HTR kwiiseli ze-endothelial, iiseli ze-muscle ezigudileyo kunye iiseli zomzimba.Pacala et al.Umphumo we-mitotic we-5-HT kwiiseli ze-vascular endothelial zafundwa, kwaye amandla okukhuthaza ukukhula kwemithambo yegazi eyonakalisiweyo ngokuvuselela i-angiogenesis yagqitywa.Indlela ezi nkqubo zilawulwa ngayo ayicacanga ngokupheleleyo, kodwa inokubandakanya ukuhlukana kweendlela ezimbini zomqondiso kwi-microcircuit yezicubu ukulawula imisebenzi yeeseli ze-vascular endothelial kunye neeseli ze-muscle ezigudileyo, i-fibroblasts kunye neeseli zomzimba ngokusebenzisa i-5-HT receptors ezithile kwezi seli. .Umsebenzi we-autocrine weplatelet 5-HT emva kokusebenza kweplatelet ichazwe [REF].Ukukhutshwa kwe-5-HT kwandisa ukusebenza kweeplatelet kunye nokuqeshwa kweeplatelet ezijikelezayo, ezikhokelela ekusebenzeni kwe-signal cascade reactions kunye ne-upstream effectors ezixhasa i-platelet reactivity.
Immunomodulatory 5-HT isiphumo
Ubungqina obuninzi nangakumbi bubonisa ukuba i-serotonin inokudlala indima kwi-5HTR eyahlukileyo njenge-modulator yomzimba.Ngokutsho kwe-5HTR echazwe kwii-leukocytes ezahlukeneyo ezibandakanyekayo kwi-reaction inflammatory, i-platelet-derived 5-HT isebenza njengomlawuli we-immune kuzo zombini izistim zokuzivikela ezizalwa kunye neziguquguqukayo.I-5-HT inokuvuselela ukwanda kwe-Treg kunye nokulawula imisebenzi yeeseli ze-B, iiseli ezibulalayo zendalo kunye ne-neutrophils ngokugaya i-DC kunye ne-monocytes kwindawo yokuvuvukala.Uphando olutshanje lubonise ukuba i-platelet-derived 5-HT inokulawula umsebenzi weeseli zokuzivikela phantsi kweemeko ezithile.Ngoko ke, usebenzisa i-C-PRP, i-concentration yeplatelet inkulu kune-1 × 10 6 / µ L inokunceda kakhulu ukuthutha i-concentration ye-5-HT evela kwiiplatelet ezinkulu ukuya kwizicubu.Kwi-microenvironment ebonakaliswe ngamacandelo avuthayo, i-PRP inokusebenzisana kunye neeseli ezininzi ze-immune ezidlala indima ephambili kwezi pathologies, ezinokuchaphazela iziphumo zeklinikhi.
Umzobo obonisa i-multifaceted 5-HT impendulo emva kokusebenza kweeplatelet ze-PRP ezivuthayo.Emva kokusebenza kweeplatelet, iiplatelet zikhulula iigranules zazo, kubandakanywa i-5-HT kwiigranules ezixineneyo, ezinoluhlu olubanzi lweempembelelo ezihlukeneyo kwiiseli ezikhuselayo, iiseli ze-endothelial kunye neeseli ze-muscle ezigudileyo.Izifinyezo: i-SMC: iiseli ze-muscle ezigudileyo, i-EC: iiseli ze-endothelial, i-Treg: i-lymphocytes ye-T eqhelekileyo, i-M Φ: i-Macrophages, i-DC: iiseli ze-dendritic, i-IL: i-interleukin, i-IFN- γ: I-Interferon γ。 Uhlengahlengiso kwaye uguqulelwe kwi-Everts et al.kunye noHull et al.
Impembelelo ye-analgesic ye-PRP
Iiplatelet ezisetyenzisiweyo ziya kukhulula abalamli abaninzi be-pro-inflammatory kunye ne-anti-inflammatory, abangenakubangela intlungu kuphela, kodwa nokunciphisa ukuvuvukala kunye nentlungu.Xa sele isetyenzisiwe, i-platelet dynamics ye-PRP itshintsha i-microenvironment ngaphambi kokulungiswa kwezicubu kunye nokuvuselelwa ngeendlela ezahlukeneyo eziyinkimbinkimbi ezinxulumene ne-anabolism kunye ne-catabolism, ukwanda kweeseli, ukuhlukana kunye nokulawulwa kwe-stem cell.Ezi mpawu ze-PRP zikhokelela ekusebenziseni i-PRP kwiimeko ezahlukeneyo ze-pathological zeklinikhi ngokuqhelekileyo zihambelana neentlungu ezingapheliyo (ezifana nokulimala kwezemidlalo, isifo samathambo, isifo somgogodla kunye nesilonda esinzima esinzima), nangona indlela echanekileyo ayizange igqitywe ngokupheleleyo.
Kwi-2008, u-Evertz et al.Lulingo lokuqala olulawulwa ngokungenamkhethe ukunika ingxelo ngesiphumo se-analgesic yokulungiswa kwe-PRP, elungiselelwe ukusuka kumqolo omdaka wesantya se-autologous erythrocyte sedimentation kwaye isebenze nge-autologous thrombin emva kotyando lwamagxa.Baye baqaphela ukunciphisa okubonakalayo kumanqaku e-analogue scale scale, ukusetyenziswa kwe-opioid esekelwe kwi-analgesics, kunye nokubuyisela ngempumelelo emva kokuhlinzwa.Kuyaphawuleka ukuba zibonakalisa umphumo we-analgesic we-platelet esebenzayo kwaye uqikelele kwindlela yeeplatelet ezikhupha i-5-HT.Ngamafutshane, iiplatelet zilele kwi-PRP esanda kulungiswa.Emva kokusebenza kweeplatelet ngokuthe ngqo okanye ngokungathanga ngqo (i-tissue factor), iiplatelet zitshintsha imilo kwaye zivelise ubuxoki ngokwaneleyo ukukhuthaza ukuhlanganiswa kweeplatelet.Emva koko, bakhupha i-intracellular α- Kwaye amasuntswana ashinyeneyo.Izicubu eziphathwe nge-PRP esebenzayo ziya kuhlaselwa yi-PGF, i-cytokines kunye nezinye i-lysosomes zeplatelet.Ngokukodwa ngakumbi, xa iincinci ezixineneyo zikhupha iziqulatho zazo, ziya kukhulula inani elikhulu le-5-HT elawula intlungu.Kwi-C-PRP, ukugxininiswa kweplatelet yi-5 kumaxesha e-7 aphezulu kunokuba kwi-peripheral blood.Ngoko ke, ukukhululwa kwe-5-HT kwiiplatelet yi-astronomical.Okubangela umdla kukuba, uSprott et al.Ingxelo yabona ukuba intlungu ikhululwe kakhulu emva kwe-acupuncture kunye ne-moxibustion, ukuxinwa kweplatelet ephuma kwi-5-HT yancitshiswa kakhulu, kwaye ke inqanaba le-plasma ye-5-HT yanda.
Kwi-peripheral, iiplatelet, iiseli zemast kunye neeseli ze-endothelial ziya kukhulula i-5-HT engapheliyo ngexesha lokulimala kwezicubu okanye ukwenzakala kotyando.Kuyathakazelisa ukuba iintlobo ezahlukeneyo ze-5-HT ze-receptors ze-neurons zifunyenwe kwindawo ye-peripheral, eqinisekisa ukuba i-5-HT inokuphazamisa ukuhanjiswa kwe-nociceptive kwindawo ye-peripheral.Ezi zifundo zibonisa ukuba i-5-HT inokuchaphazela ukuhanjiswa kwe-nociceptive yezicubu ze-peripheral ngokusebenzisa i-5-HT1, 5-HT2, 5-HT3, 5-HT4 kunye ne-5-HT7 receptors.
Inkqubo ye-5-HT imele inkqubo enamandla enokunciphisa kunye nokwandisa iqondo lentlungu emva kokuvuselela okuyingozi.Ukulawulwa kwe-central and peripheral of signals nociceptive kunye notshintsho kwinkqubo ye-5-HT iye yaxelwa kwizigulane ezinentlungu engapheliyo.Kwiminyaka yakutshanje, inani elikhulu lezifundo ligxininise indima ye-5-HT kunye ne-receptors echaphazelekayo ekuqhubeni nasekulawuleni ulwazi oluyingozi, okubangelwa iziyobisi ezifana ne-serotonin reuptake inhibitors (SSRI) ekhethiweyo.Eli chiza livimbela ukuphinda kuthathwe i-serotonin kwi-presynaptic neurons emva kokukhululwa kwe-serotonin.Ichaphazela ubude kunye nokuqina konxibelelwano lwe-serotonin kwaye yolunye unyango lweentlungu ezingapheliyo.Uphando olongezelelweyo lweklinikhi luyadingeka ukuze uqonde ngokucacileyo indlela ye-molecular ye-PRP-derived 5-HT yokulawulwa kweentlungu kwizifo ezingapheliyo kunye nezifo eziphazamisayo.
Enye idatha yokusombulula umphumo onokuthi ube ne-analgesic ye-PRP inokufumaneka emva kovavanyo lwemodeli yezilwanyana ze-analgesic.Izigqibo zamanani othelekiso kwezi modeli zingumngeni kuba ezi zifundo ziqulethe izinto ezininzi eziguquguqukayo.Nangona kunjalo, ezinye izifundo zeklinikhi ziye zajongana nemiphumo ye-nociceptive kunye ne-analgesic ye-PRP.Izifundo ezininzi zibonise ukuba izigulane ezifumana unyango lwe-tendinosis okanye i-rotator cuff iinyembezi zineentlungu ezincinci.Ngokwahlukileyo, ezinye izifundo ezininzi zibonise ukuba i-PRP inokunciphisa okanye isuse intlungu yezigulane ezine-tendon degeneration, i-OA, i-plantar fasciitis kunye nezinye izifo zeenyawo kunye ne-ankle.Ingqungquthela yokugqibela yeplatelet kunye nokwakheka kweeseli ze-biological ziye zachongwa njengeempawu eziphambili ze-PRP, ezinceda ukujonga umphumo ohambelanayo we-analgesic emva kokusetyenziswa kwe-PRP.Ezinye izinto eziguquguqukayo ziquka indlela yokuhanjiswa kwe-PRP, iteknoloji yesicelo, iprotocol activation protocol, inqanaba lomsebenzi we-biological we-PGF kunye ne-cytokines ekhutshwe, uhlobo lwe-tissue yesicelo se-PRP kunye nohlobo lokulimala.
Kuyaphawuleka ukuba i-Kuffler yasombulula amandla e-PRP ekunciphiseni intlungu kwizigulane ezinobunzima obuncinci ukuya kwiintlungu ezingapheliyo ze-neuropathic, okwesibini kwi-nerve eyonakalisiweyo engahlaziyiyo.Injongo yolu phononongo kukuphanda ukuba intlungu ye-neuropathic ingancitshiswa okanye ikhutshwe ngenxa ye-PRP yokukhuthaza ukuvuselelwa kwe-axonal kunye ne-target nerve reinnervation.Okumangalisayo kukuba, phakathi kwezigulane ezifumana unyango, iintlungu ze-neuropathic zisacinywa okanye zincitshiswe ubuncinane kwiminyaka emithandathu emva kokuhlinzwa.Ukongezelela, zonke izigulane zaqala ukukhulula intlungu kwiiveki ezintathu emva kokusetyenziswa kwe-PRP.
Kungekudala, iziphumo ezifanayo ze-PRP ze-analgesic ziye zabonwa kwintsimi yenxeba emva kokusebenza kunye nokunyamekela kwesikhumba.Kuyathakazelisa ukuba, ababhali baxela imiba ye-physiological yentlungu yesilonda ehambelana nokulimala kwe-vascular kunye ne-skin tissue hypoxia.Baphinde baxoxe ngokubaluleka kwe-angiogenesis ekuphuculeni i-oxygenation kunye nokuhanjiswa kwezondlo.Uphononongo lwabo lubonise ukuba xa kuthelekiswa neqela lolawulo, izigulane ezifumana unyango lwe-PRP zineentlungu ezincinci kwaye zanda kakhulu i-angiogenesis.Ekugqibeleni, uJoal kunye noogxa bakhe benza uphononongo olucwangcisiweyo kunye nohlalutyo lwe-meta kwaye bagqiba ukuba i-PRP inokunciphisa intlungu emva kokusebenzisa i-PRP kwizibonakaliso zamathambo, ngakumbi kwizigulane ezifumana i-epicondylitis yangaphandle kunye ne-knee OA unyango.Ngelishwa, olu pho nonongo aluzange lucacise iziphumo zeeseli ezimhlophe zegazi, i-concentration yeplatelet okanye ukusetyenziswa kwe-activators ye-platelet exogenous, kuba ezi ziguquko ziya kuchaphazela ukusebenza ngokupheleleyo kwe-PRP.Olona gxininiso lweplatelet ye-PRP luphezulu kakhulu alucaci.Kwimodeli yegundane ye-tendinosis, i-concentration ye-platelet yayiyi-1.0 × 10 6 / μ Kwi-L, intlungu inokukhululeka ngokupheleleyo, ngelixa intlungu ebangelwa yi-PRP kunye nesiqingatha soxinzelelo lweplatelet iyancipha kakhulu.Ngoko ke, sikhuthaza izifundo ezininzi zeklinikhi ukuphanda imiphumo ye-analgesic yamalungiselelo ahlukeneyo e-PRP.
I-PRP kunye ne-angiogenesis effect
Amalungiselelo e-C-PRP kwiyeza elichanekileyo lokuvuselela avumela ukuhanjiswa kwee-biomolecules ezikhutshwe ngamaqondo aphezulu eeplatelet asebenze kwiindawo ezijoliswe kuzo.Ke ngoko, kuye kwaqaliswa iindlela ezahlukeneyo zokusabela kwe-cascade, ezinegalelo kulawulo lokhuselo lomzimba kwindawo, inkqubo yokuvuvukala kunye ne-angiogenesis ukukhuthaza ukuphilisa kunye nokulungiswa kwezicubu.
I-Angiogenesis yinkqubo eguquguqukayo enamanyathelo amaninzi ebandakanya ukuhluma kunye ne-microvessels yezicubu ukusuka kwimithambo yegazi esele ikhona.I-Angiogenesis iqhubekile ngenxa yeendlela ezahlukeneyo zezinto eziphilayo, kubandakanywa ukufuduka kweeseli ze-endothelial, ukwanda, ukuhlukana kunye nokwahlula.Ezi nkqubo zeselula ziyimfuneko yokwenziwa kwemithambo yegazi emitsha.Zibalulekile ekukhuleni kwemithambo yegazi ekhoyo ngaphambili ukubuyisela ukuhamba kwegazi kunye nokuxhasa umsebenzi ophezulu we-metabolic wokulungiswa kwezicubu kunye nokuvuselelwa kwezicubu.Le mithambo yegazi emitsha ivumela ukuhanjiswa kweoksijini kunye nezondlo, kunye nokususwa kweemveliso ezivela kwizicubu eziphathwayo.
Umsebenzi we-Angiogenesis ulawulwa ngokuvuselela i-angiogenic factor VEGF kunye ne-anti-angiogenic factor (umzekelo, i-angiostatin kunye ne-thrombospondin-1 [TSP-1]).Kwi-microenvironment egulayo kunye neyonakalisiwe (kubandakanywa ukunyanzeliswa kwe-oksijeni ephantsi, i-pH ephantsi kunye nenqanaba eliphezulu le-lactic acid), izinto ze-angiogenic zendawo ziya kubuyisela umsebenzi we-angiogenesis.
Imithombo yeendaba ezininzi ezinyibilikayo zeplatelet, njengesiseko seFGF kunye ne-TGF- β Kwaye i-VEGF inokuvuselela iiseli ze-endothelial ukuvelisa imithambo yegazi emitsha.I-Landdown kunye ne-Fortier ibike iziphumo ezahlukeneyo ezinxulumene nokubunjwa kwe-PRP, kubandakanywa nemithombo ye-intraplatelet yabalawuli abaninzi be-angiogenic.Ukongezelela, bagqiba ukuba ukwanda kwe-angiogenesis kuncedisa ukuphulukiswa kwesifo se-MSK kwiindawo ezine-vascularization embi, njenge-meniscus tear, ukulimala kwe-tendon kunye nezinye iindawo ezine-vascularization embi.
Ukukhuthaza kunye ne-anti-angiogenic platelet properties
Kwiminyaka embalwa edlulileyo, izifundo ezipapashiweyo zibonise ukuba iiplatelet zidlala indima ephambili kwi-hemostasis yokuqala, ukubunjwa kwe-clot, ukukhula kunye nokukhululwa kwe-cytokine, kunye nokulawulwa kwe-angiogenesis njengenxalenye yenkqubo yokulungiswa kwezicubu.Ngokumangalisayo, i-PRP α- I-granules iqulethe i-arsenal yezinto ezikhulayo ze-pro-angiogenic, iiprotheni ezichasayo kunye ne-cytokines (ezifana ne-PF4, i-plasminogen activator inhibitor-1 kunye ne-TSP-1), kwaye ijolise ekukhululweni kwezinto ezithile ezidlala indima. .Indima kwi-angiogenesis.Ngoko ke, indima ye-PRP ekulawuleni ukulawulwa kwe-angiogenesis inokuchazwa ngokusebenza kwe-cell cell receptors, i-TGF- β Qalisa i-pro-angiogenic kunye ne-anti-angiogenic reactions.Ukukwazi kweeplatelet ukusebenzisa indlela ye-angiogenesis kuye kwaqinisekiswa kwi-angiogenesis ye-pathological kunye ne-tumor angiogenesis.
Platelet-derived angiogenic growth factor and anti-angiogenic growth factor, derived from α- Kwaye ezishinyeneyo kunye iimolekyuli ezincamathelayo.Okona kubaluleke kakhulu, kuyamkelwa ngokubanzi ukuba isiphumo esipheleleyo seeplatelet kwi-angiogenesis yi-pro-angiogenic kunye ne-stimulating.Kulindeleke ukuba unyango lwe-PRP luya kulawula ukufakwa kwe-angiogenesis, eya kuba negalelo kwisiphumo sonyango lwezifo ezininzi, ezifana nokuphulukiswa kwesilonda kunye nokulungiswa kwezicubu.Ukulawulwa kwe-PRP, ngokukodwa ukulawulwa kwe-PGF ephezulu kunye nezinye ii-cytokines zeplatelet, kunokubangela i-angiogenesis, i-angiogenesis kunye ne-arteriogenesis, kuba i-stromal cell-derived factor 1a ibophelela kwi-CXCR4 receptor kwiiseli ze-progenitor endothelial.UBill et al.Kucetyiswa ukuba i-PRP ikhulise i-ischemic neovascularization, enokuthi ibe ngenxa yokuvuselela i-angiogenesis, i-angiogenesis kunye ne-arteriogenesis.Kwimodeli yabo ye-in vitro, ukwanda kweeseli ze-endothelial kunye nokwakheka kwe-capillary kwabangelwa inani elikhulu lee-PDG ezahlukeneyo, apho i-VEGF yayiyeyona nto ivuselela i-angiogenic.Enye into ebalulekileyo nebalulekileyo yokubuyisela indlela ye-angiogenesis yintsebenziswano phakathi kwee-PGF ezininzi.Richardson et al.Kuye kwangqinwa ukuba umsebenzi we-synergistic we-angiogenic factor platelet-derived growth factor-bb (PDGF-BB) kunye ne-VEGF ibangele ukusekwa ngokukhawuleza kwenethiwekhi ye-vascular ekhulile xa kuthelekiswa nomsebenzi wokukhula komntu ngamnye.Isiphumo esidityanisiweyo sale miba sisandul’ ukuqinisekiswa kuphononongo malunga nokwandiswa kwe-cerebral collateral circulation kwiimpuku ezine-hypoperfusion yexesha elide.
Okona kubaluleke kakhulu, uphononongo lwe-in vitro lulinganisa isiphumo sokwanda kweeseli ze-umbilical vein endothelial cell kunye nokugxilwa kweplatelet eyahlukeneyo ekukhetheni isixhobo sokulungiselela i-PRP kunye nesicwangciso sedosi yeplatelet, kwaye iziphumo zabonisa ukuba elona thamo lifanelekileyo leplatelet yi-1.5 × 10 6 platelets/ μ 50. Ukukhuthaza i-angiogenesis.Uxinzelelo lweplatelet ephezulu kakhulu inokuthintela inkqubo ye-angiogenesis, ngoko ke umphumo ubi.
Ukuguga kweeseli, ukuguga kunye ne-PRP
Ukukhula kweeseli kunokuphenjelelwa zizivuseleli ezahlukahlukeneyo.Le yinkqubo apho iiseli ziyeka ukuhlukana kwaye zitshintshe i-phenotypic ekhethekileyo ukukhusela ukukhula okungathintekiyo kweeseli ezonakalisiweyo, ezidlala indima ebalulekileyo ekuthinteleni umhlaza.Kwinkqubo yokuguga komzimba, ukuguga kokuphindaphinda kweeseli kuya kukhuthaza ukuguga kweeseli, kwaye amandla okuhlaziya ii-MSCs aya kuncitshiswa.
Iziphumo zokuguga kunye nokuguga kweeseli
Kwi-vivo, iintlobo ezininzi zeeseli ziya kuguga kwaye ziqokelele kwizicubu ezahlukeneyo ngexesha lokuguga, phakathi kwazo kukho inani elikhulu leeseli zokuguga.Ukuqokelela kweeseli eziguga kubonakala kunyuka ngokunyuka kweminyaka, umonakalo we-immune system, umonakalo wezicubu okanye izinto ezinxulumene noxinzelelo.Indlela yokuguga kwamaselula ichongiwe njengento ye-pathogenic yezifo ezinxulumene neminyaka yobudala, njenge-osteoarthritis, i-osteoporosis kunye ne-intervertebral disc degeneration.Iindidi ezahlukeneyo zokuvuselela ziya kwandisa ukuguga kweeseli.Ekuphenduleni, i-senescence-related secretory phenotype (SASP) iya kukhupha i-concentrations ephezulu yeeseli zeprotheyini kunye ne-cytokines.Le phenotype ekhethekileyo ihambelana neeseli zokuguga, apho zikhupha amanqanaba aphezulu e-cytokines evuthayo (njenge-IL-1, IL-6, IL-8), izinto zokukhula (ezifana ne-TGF- β, HGF, VEGF, PDGF), MMP, kunye necathepsin.Xa kuthelekiswa nabantu abatsha, i-SAPS ibonakaliswe ukuba ikhula ngokukhula, ngenxa yokuba inkqubo yokuzinza iyatshatyalaliswa, nto leyo ekhokelela ekugugeni kweeseli kunye nokuncipha kwamandla okuhlaziya.Ngokukodwa, kwizifo ezidibeneyo kunye nezifo ze-skeletal muscle.Kule nkalo, ukuguga kwe-immune kuthathwa njengotshintsho oluphawulekayo kwi-secretion spectrum ye-immune cells, ebonisa ukuba ukuxinwa kwe-TNF-a, IL-6 kunye / okanye i-Il-1b kwanda, okukhokelela ekuvukeni okuphantsi okungapheliyo.Kuyafaneleka ukuba uqaphele ukuba i-stem cell dysfunction inxulumene neendlela ezizimeleyo ezingezona zeselula, ezifana neeseli eziguga, ngokukodwa ukuveliswa kwezinto eziphazamisayo kunye ne-anti-regenerative nge-SASP.
Ngokuchasene noko, i-SASP inokuvuselela iplastiki yeeseli kunye nokuhlelwa ngokutsha kweeseli ezikufutshane.Ukongeza, i-SASP inokuququzelela unxibelelwano kunye nabalamli abahlukeneyo bomzimba kwaye isebenze iiseli zokhuselo lomzimba ukukhuthaza ukucocwa kweeseli ezigugayo.Ukuqonda indima kunye nomsebenzi weeseli eziguga kuya kuba negalelo ekuphulukiseni nasekuhlaziyeni izicubu zemisipha ye-MSK kunye namanxeba angapheliyo.
Kuyaphawuleka ukuba uRitcka et al.Uphononongo olubanzi lwenziwa, kwaye indima ephambili kunye nenzuzo ye-SASP ekukhuthazeni iplastiki yeeseli kunye nokuvuselelwa kwezicubu zafunyanwa, kwaye ingcamango yokunikezelwa konyango lwexeshana lweeseli eziguga yaqaliswa.Bakhankanye ngononophelo ukuba ukwaluphala ubukhulu becala kuyinkqubo enenzuzo nehlaziyayo.
Ukuguga kweeseli kunye nokubakho kwe-PRP
Njengoko inani leeseli ze-stem liyancipha, ukuguga kuya kuchaphazela ukusebenza kweeseli ze-stem.Ngokufanayo, kubantu, iimpawu ze-stem cell (ezifana nokomisa, ukwanda kunye nokwahlula) nazo ziyancipha ngokukhula.UWang noNirmala baxele ukuba ukuguga kuya kunciphisa iimpawu ze-tendon cell stem cell kunye nenani le-reaceiver factor receptors.Uphononongo lwezilwanyana lubonise ukuba ukuxinwa kwePDGF kumahashe amancinci kwakuphezulu.Baye bagqiba ukuba ukwanda kwenani le-GF receptors kunye nenani le-GF kubantu abancinci banokuba nempendulo engcono yeselula kunyango lwe-PRP kunabantu abadala kubantu abancinci.Ezi ziphumo zityhila ukuba kutheni unyango lwe-PRP lunokungasebenzi kakuhle okanye lungasebenzi kwizigulane ezisele zikhulile ezineeseli ze-stem ezimbalwa kunye "nomgangatho ophantsi".Kuye kwafakazelwa ukuba inkqubo yokuguga ye-cartilage yokuguga iguqulwa kwaye ixesha lokuphumla le-chondrocytes linyuswa emva kwe-injection ye-PRP.Jia et al.Isetyenziselwa ukufunda i-mouse dermal fibroblasts in vitro photoaging, kunye nangaphandle konyango lwe-PRP, ukucacisa indlela yokuchasana kwe-PGF kulo mzekelo.Iqela le-PRP libonise umphumo othe ngqo kwi-matrix ye-extracellular, uhlobo olwandisiweyo lwe-collagen kunye nokunciphisa i-synthesis ye-metalloproteinases, ebonisa ukuba i-PRP inokumelana nokuguga kweeseli, kunye nesifo se-MSK esiwohlokayo.
Kwesinye isifundo, i-PRP yayisetyenziselwa ukuqokelela iiseli ze-bone marrow ezikhulile kwiigundane ezindala.Kuye kwagqitywa ukuba i-PRP inokubuyisela imisebenzi eyahlukeneyo ye-stem cell ukusuka ekuguga, njengokunyuka kweeseli kunye nokwakhiwa kwekholoni, kunye nokuvuselela abamakishi abanxulumene nokuguga kweeseli.
Kungekudala, u-Oberlohr kunye noogxa bakhe bafunde ngokubanzi indima yokuguga kweeseli ekunciphiseni ukuvuselelwa kwemisipha, kwaye bavavanya i-PRP kunye ne-platelet-poor plasma (PPP) njengokhetho lwe-biological unyango lokulungiswa kwemisipha.Baye bacinga ukuba unyango lwe-PRP okanye i-PPP yokulungiswa kwemisipha ye-skeletal iya kusekelwe kwizinto ze-biological ezilungiselelwe i-SASP impawu ezithile zeeseli kunye nezinye izinto ezikhokelela ekuphuhlisweni kwe-fibrosis.
Kunengqiqo ukukholelwa ukuba ngaphambi kokusetyenziswa kwe-PRP, ukuguga kweseli ekujoliswe kuyo kunokuphucula iimpawu zokuhlaziywa kwe-biological treatment efficacy ngokunciphisa izinto ze-SASP zendawo.Kuye kwacetyiswa ukuba enye inketho yokuphucula iziphumo ze-PRP kunye ne-PPP yonyango yokuvuselelwa kwemisipha ye-skeletal kukukhupha ngokukhethiweyo iiseli eziguga kunye nama-scavengers aguga.Akungabazeki ukuba iziphumo zophando lwakutsha nje kwisiphumo se-PRP ekugugeni kweeseli kunye nokuguga zinomdla, kodwa zisekwinqanaba lokuqala.Ngoko ke, akukho ngqiqweni ukwenza naziphi na iingcebiso ngeli xesha.
(Imixholo yeli nqaku ishicilelwe, kwaye asiboneleli nasiphi na isiqinisekiso esicacileyo okanye esichaziweyo sokuchaneka, ukuthembeka okanye ukugqibelela kokuqulathwe kweli nqaku, kwaye abanaxanduva ngezimvo zeli nqaku, nceda uqonde.)
Ixesha lokuposa: Mar-01-2023