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Mechanism of Platelet Rich Plasma (PRP) Therapy Promoting Tissue Healing

Niaj hnub no, lub tswv yim hu ua PRP thawj zaug tau tshwm sim hauv thaj chaw hematology hauv xyoo 1970s.Hematologists tau tsim lub sij hawm PRP xyoo dhau los los piav txog cov ntshav tau los ntawm cov platelet suav siab dua li tus nqi ntawm cov ntshav peripheral.Ntau tshaj kaum xyoo tom qab, PRP tau siv nyob rau hauv maxillofacial phais raws li ib daim ntawv ntawm platelet nplua nuj fibrin (PRF).Cov ntsiab lus ntawm fibrin nyob rau hauv no PRP derivative muaj nuj nqis tseem ceeb vim nws adhesiveness thiab khov kho-lub xeev cov yam ntxwv, thaum PRP muaj sustained anti-inflammatory zog thiab stimulates cell proliferation.Thaum kawg, nyob ib ncig ntawm xyoo 1990, PRP tau pib nrov.Thaum kawg, cov cuab yeej no tau pauv mus rau lwm qhov chaw kho mob.Txij thaum ntawd los, qhov zoo ntawm biology no tau kawm dav dav thiab siv rau kev kho mob ntawm ntau yam kev raug mob musculoskeletal ntawm cov kws ncaws pob kws tshaj lij, uas tau txhawb nqa nws txoj kev xav thoob plaws hauv xov xwm.Ntxiv nrog rau kev ua haujlwm zoo hauv orthopedics thiab kis las tshuaj, PRP kuj tseem siv rau hauv ophthalmology, gynecology, urology thiab cardiology, pediatrics thiab phais yas.Nyob rau hauv xyoo tas los no, PRP kuj tau txais kev qhuas los ntawm cov kws kho mob dermatologist rau nws lub peev xwm hauv kev kho mob ntawm daim tawv nqaij, kho caws pliav, kho cov ntaub so ntswg, tawv nqaij rejuvenation thiab txawm plaub hau poob.

PRP

Xav txog qhov tseeb tias PRP tuaj yeem ncaj qha kho cov txheej txheem kho mob thiab cov txheej txheem inflammatory, nws yog ib qho tsim nyog los qhia txog kev kho mob cascade raws li kev siv.Cov txheej txheem kho tau muab faib ua plaub theem hauv qab no: hemostasis;Kev mob;Cell thiab matrix proliferation, thiab thaum kawg qhov txhab kho.

 

Hniav Hniav

Cov ntaub so ntswg kho cascade cov tshuaj tiv thaiv yog qhib, uas ua rau platelet aggregation Lub tsim ntawm cov hlab ntsha thiab kev loj hlob ntawm ib ntus extracellular matrix (ECM).Tom qab ntawd, platelets ua raws li cov collagen thiab ECM protein, ua rau kev tso tawm ntawm bioactive molecules tam sim no nyob rau hauv a-granules.Platelets muaj ntau yam bioactive molecules, nrog rau kev loj hlob yam tseem ceeb, cov tshuaj khomob thiab cytokines, nrog rau cov kws kho mob proinflammatory, xws li prostaglandin, prostate cyclin, histamine, thromboxane, serotonin thiab bradykinin.

Cov theem kawg ntawm cov txheej txheem kho yog nyob ntawm qhov kho qhov txhab.Kev kho cov ntaub so ntswg nruj nruj kom tsim kom muaj qhov sib npaug ntawm cov tshuaj anabolic thiab catabolic.Nyob rau theem no, platelet-derived growth factor (PDGF) thiab transforming growth factor (TGF- β) Fibronectin thiab fibronectin txhawb kev loj hlob thiab tsiv teb tsaws ntawm fibroblasts, nrog rau cov synthesis ntawm ECM Cheebtsam.Txawm li cas los xij, lub sij hawm ntawm qhov txhab loj hlob nyob ntawm qhov loj ntawm qhov mob ntawm qhov txhab, tus yam ntxwv ntawm tus kheej thiab lub peev xwm kho kom zoo ntawm cov ntaub so ntswg raug mob.Qee cov kab mob pathophysiological thiab metabolic tuaj yeem cuam tshuam rau cov txheej txheem kho, xws li cov ntaub so ntswg ischemia, hypoxia, kab mob, kev loj hlob tsis zoo, thiab txawm tias muaj cov kab mob metabolic.

Lub proinflammatory microenvironment cuam tshuam nrog cov txheej txheem kho.Ntau qhov nyuaj yog tias cov kev ua haujlwm siab protease inhibits qhov kev ua ntawm kev loj hlob zoo (GF).Ntxiv rau nws cov mitotic, angiogenic thiab chemotactic zog, PRP kuj yog ib qho chaw nplua nuj ntawm ntau yam kev loj hlob.Cov biomolecules no tuaj yeem tiv thaiv cov teeb meem tsis zoo hauv cov ntaub so ntswg los ntawm kev tswj cov kab mob o thiab tsim cov anabolic stimuli.Xav txog cov yam ntxwv no, cov kws tshawb fawb yuav pom muaj peev xwm kho tau ntau yam kev raug mob nyuaj.

Ntau yam kab mob, tshwj xeeb tshaj yog cov kab mob musculoskeletal, muaj zog nyob ntawm cov khoom siv roj ntsha uas tswj cov txheej txheem inflammatory, xws li PRP rau kev kho mob osteoarthritis.Hauv qhov no, kev noj qab haus huv ntawm pob txha pob txha pob txha nyob ntawm qhov sib npaug ntawm cov tshuaj anabolic thiab catabolic.Nrog rau lub hauv paus ntsiab lus no, kev siv qee cov tshuaj lom neeg muaj txiaj ntsig zoo tuaj yeem ua pov thawj ua tiav hauv kev ua tiav kev noj qab haus huv.PRP vim nws tso tawm platelets α- Kev loj hlob yam muaj nyob rau hauv granules yog dav siv los tswj lub peev xwm ntawm cov ntaub so ntswg hloov, uas kuj txo qhov mob.Qhov tseeb, ib lub hom phiaj tseem ceeb ntawm kev kho PRP yog kom tsis txhob muaj cov kab mob loj thiab catabolic microenvironment thiab txhawb kev hloov pauv mus rau cov tshuaj tiv thaiv kab mob.Lwm tus kws sau ntawv yav dhau los tau ua pov thawj tias thrombin qhib PRP nce qhov tso tawm ntawm ntau cov roj ntsha molecules.Cov yam tseem ceeb no muaj xws li hepatocyte growth factor (HGF) thiab qog necrosis factor (TNF- α), Transforming growth factor beta1 (TGF- β 1), vascular endothelial growth factor (VEGF) thiab epidermis Growth factor (EGF).Lwm cov kev tshawb fawb tau pom tias PRP txhawb kev nce qib ntawm hom II collagen thiab aggrecan mRNA qib, thaum txo qhov inhibition ntawm pro-inflammatory cytokine interleukin - (IL) 1 ntawm lawv.Nws kuj tau hais tias vim yog HGF thiab TNF- α [28] PRP tuaj yeem pab tsim kom muaj kev tiv thaiv kab mob.Ob qho tib si ntawm cov tshuaj molecular no txo ​​cov khoom siv hluav taws xob nuclear kappaB (NF- κВ) Los tiv thaiv kev ua haujlwm thiab kev qhia;Thib ob, los ntawm TGF- β 1 qhia kuj tiv thaiv monocyte chemotaxis, yog li tawm tsam TNF- α Cov nyhuv ntawm kev hloov pauv ntawm chemokines.HGF zoo li ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kev mob tshwm sim los ntawm PRP.Qhov no muaj zog tiv thaiv kab mob cytokine rhuav tshem NF- κ B kev taw qhia txoj hauv kev thiab proinflammatory cytokine qhia inhibit inflammatory teb.Tsis tas li ntawd, PRP tseem tuaj yeem txo cov qib siab ntawm nitric oxide (NO).Piv txwv li, hauv pob txha pob txha, qhov nce ntawm NO concentration tau ua pov thawj los inhibit collagen synthesis thiab induce chondrocyte apoptosis, thaum nce cov synthesis ntawm matrix metalloproteinases (MMPs), yog li txhawb kev hloov pauv ntawm catabolism.Nyob rau hauv cov nqe lus ntawm cell degeneration, PRP kuj suav hais tias yuav muaj peev xwm tswj tau autophagy ntawm cov cell tshwj xeeb.Thaum mus txog lub xeev laus kawg, qee pawg ntawm tes poob lub peev xwm ntawm lub xeev zoo li qub thiab rov ua dua tus kheej.Txawm li cas los xij, kev tshawb fawb tsis ntev los no tau pom tias kev kho PRP tuaj yeem thim rov qab cov xwm txheej tsis zoo no.Moussa thiab cov npoj yaig tau ua pov thawj tias PRP tuaj yeem ua rau muaj kev tiv thaiv chondrocytes los ntawm kev nce autophagy thiab anti-inflammatory markers, thaum txo cov apoptosis ntawm tib neeg osteoarthritis pob txha mos.Garcia Pratt et al.Nws tau tshaj tawm tias autophagy txiav txim qhov kev hloov pauv ntawm qhov so thiab kev laus txoj hmoo ntawm cov leeg qia hlwb.Cov kws tshawb fawb ntseeg tias, hauv vivo, qhov normalization ntawm kev sib xyaw ua ke ntawm autophagy zam kev txuam nrog kev puas tsuaj hauv lub cev thiab tiv thaiv kev laus thiab kev ua haujlwm tsis zoo ntawm cov hlwb satellite.Txawm hais tias nyob rau hauv cov laus tib neeg qia hlwb, xws li tsis ntev los no, Parrish thiab Rodes kuj tau koom tes tseem ceeb, ntxiv nthuav tawm cov peev xwm tiv thaiv kab mob ntawm PRP.Lub sijhawm no, kev tsom mus rau kev sib cuam tshuam ntawm platelets thiab neutrophils.Hauv lawv qhov kev tshawb nrhiav, cov kws tshawb fawb tau piav qhia tias cov platelets tso tawm los ntawm arachidonic acid tau nqus los ntawm neutrophils thiab hloov mus rau hauv leukotrienes thiab prostaglandins, uas yog lub npe hu ua inflammatory molecules.Txawm li cas los xij, kev sib cuam tshuam ntawm platelet neutrophil tso cai rau cov leukotriene hloov mus rau lipoproteins, uas tau raug pov thawj tias nws yog ib qho tshuaj tiv thaiv kab mob zoo uas tuaj yeem txo qis kev ua kom cov neutrophils thiab tiv thaiv kev lim ntshav, thiab txhawb kev xeeb tub mus rau theem kawg ntawm kev kho mob cascade.

Lub proinflammatory microenvironment cuam tshuam nrog cov txheej txheem kho.Ntau qhov nyuaj yog tias cov kev ua haujlwm siab protease inhibits qhov kev ua ntawm kev loj hlob zoo (GF).Ntxiv rau nws cov mitotic, angiogenic thiab chemotactic zog, PRP kuj yog ib qho chaw nplua nuj ntawm ntau yam kev loj hlob.Cov biomolecules no tuaj yeem tiv thaiv cov teeb meem tsis zoo hauv cov ntaub so ntswg los ntawm kev tswj kev mob ntxiv thiab tsim kom muaj kev txhawb nqa anabolic.

 

Cell Factor

Cytokines hauv PRP ua lub luag haujlwm tseem ceeb hauv kev tswj cov txheej txheem kho cov ntaub so ntswg thiab tswj kev puas tsuaj.Anti-inflammatory cytokines yog ntau yam ntawm biochemical molecules uas kho cov lus teb ntawm proinflammatory cytokines, feem ntau induced los ntawm activated macrophages.Anti-inflammatory cytokines cuam tshuam nrog tshwj xeeb cytokine inhibitors thiab soluble cytokine receptors los tswj qhov mob.Interleukin (IL) - 1 receptor antagonists, IL-4, IL-10, IL-11 thiab IL-13 yog cais raws li cov tshuaj tiv thaiv tseem ceeb, cytokines.Raws li qhov sib txawv ntawm qhov txhab, qee cov cytokines, xws li interferon, leukemia inhibitory yam, TGF- β Thiab IL-6, uas tuaj yeem ua rau muaj kev cuam tshuam los yog tiv thaiv kev mob.TNF- α, IL-1 thiab IL-18 muaj qee yam cytokine receptors, uas tuaj yeem cuam tshuam cov nyhuv proinflammatory ntawm lwm cov proteins [37].IL-10 yog ib qho zoo tshaj plaws los tiv thaiv cytokines, uas tuaj yeem tswj cov cytokines proinflammatory xws li IL-1, IL-6 thiab TNF- α, Thiab nce tswj cov tshuaj tiv thaiv kab mob.Cov txheej txheem tiv thaiv kev tswj hwm no ua lub luag haujlwm tseem ceeb hauv kev tsim khoom thiab kev ua haujlwm ntawm proinflammatory cytokines.Tsis tas li ntawd, qee cov cytokines tuaj yeem ua rau cov lus teb tshwj xeeb los txhawb cov fibroblasts, uas yog qhov tseem ceeb rau kev kho cov ntaub so ntswg.Inflammatory cytokine TGF β 1, IL-1 β, IL-6, IL-13 thiab IL-33 txhawb nqa fibroblasts kom sib txawv rau hauv myofibroblasts thiab txhim kho ECM [38].Nyob rau hauv lem, fibroblasts secrete cytokine TGF- β, IL-1 β, IL-33, CXC thiab CC chemokines txhawb inflammatory teb los ntawm activating thiab recruiting lub cev tiv thaiv kab mob xws li macrophages.Cov hlwb inflammatory ua si ntau lub luag haujlwm hauv lub qhov txhab, feem ntau yog los ntawm kev txhawb nqa qhov txhab tshem tawm - thiab biosynthesis ntawm chemokines, metabolites thiab loj hlob yam, uas yog qhov tseem ceeb rau kev tsim kho cov ntaub so ntswg tshiab.Yog li ntawd, cytokines hauv PRP ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa cell hom kho lub cev tiv thaiv kab mob thiab txhawb kev rov ua haujlwm ntawm theem inflammatory.Qhov tseeb, qee cov kws tshawb fawb tau xaiv cov txheej txheem no ua "kev mob rov ua dua tshiab", qhia tias theem inflammatory, txawm tias tus neeg mob muaj kev ntxhov siab, yog ib qho tsim nyog thiab tseem ceeb rau kev ua tiav ntawm cov txheej txheem kho cov ntaub so ntswg, suav nrog cov txheej txheem epigenetic uas ua rau mob. txhawb cell plasticity.

Lub luag haujlwm ntawm cytokines hauv fetal daim tawv nqaij o yog qhov tseem ceeb rau kev tshawb fawb ntawm cov tshuaj regenerative.Qhov sib txawv ntawm tus me nyuam hauv plab thiab cov neeg laus kho cov txheej txheem yog tias cov ntaub so ntswg puas ntsoog qee zaum rov qab mus rau lawv lub xeev qub raws li lub hnub nyoog fetal thiab cov ntaub so ntswg muaj feem xyuam.Hauv tib neeg, fetal tawv nqaij tuaj yeem rov tsim dua tshiab hauv 24 lub lis piam, thaum nyob rau hauv cov neeg laus, qhov txhab kho tuaj yeem ua rau muaj caws pliav.Raws li peb tau paub, piv nrog cov ntaub so ntswg noj qab haus huv, cov khoom siv kho tshuab ntawm cov caws pliav yog txo qis, thiab lawv cov dej num raug txwv.Kev saib xyuas tshwj xeeb yog them rau cytokine IL-10, uas pom tau hais tias muaj ntau heev hauv amniotic kua thiab fetal tawv nqaij, thiab tau raug pov thawj los ua lub luag haujlwm hauv kev kho tsis muaj caws pliav ntawm daim tawv nqaij hauv plab, txhawb nqa los ntawm cov nyhuv pleiotropic ntawm cytokine.ZgheibC et al.Kev hloov pauv ntawm fetal tawv nqaij mus rau hauv transgenic knockout (KO) IL-10 nas thiab tswj nas tau kawm.IL-10KO nas pom cov tsos mob ntawm o thiab caws pliav nyob ib ncig ntawm lub grafts, thaum lub grafts nyob rau hauv cov pab pawg neeg tswj pom tsis muaj kev hloov tseem ceeb nyob rau hauv biomechanical zog thiab tsis muaj caws pliav kho.

Qhov tseem ceeb ntawm kev tswj hwm qhov sib npaug ntawm qhov kev qhia ntawm cov tshuaj tiv thaiv thiab cov cytokines pro-inflammatory yog tias tom kawg, thaum overproduced, thaum kawg xa cov cim ntawm cell degradation los ntawm kev txo cov kev qhia ntawm qee cov noob.Piv txwv li, hauv cov tshuaj musculoskeletal, IL-1 β Down tswj SOX9, uas yog lub luag haujlwm rau pob txha mos.SOX9 tsim cov ntsiab lus tseem ceeb rau kev txhim kho pob txha mos, tswj hwm hom II collagen alpha 1 (Col2A1), thiab yog lub luag haujlwm rau kev hloov pauv hom II collagen noob.IL-1 β Thaum kawg, kev qhia ntawm Col2A1 thiab aggrecan tau txo qis.Txawm li cas los xij, kev kho mob nrog cov khoom lag luam platelet nplua nuj tau pom tias inhibit IL-1 β Nws tseem yog ib qho ua tau zoo ntawm cov tshuaj regenerative los tswj cov kev qhia ntawm collagen coding noob thiab txo cov apoptosis ntawm chondrocytes induced los ntawm proinflammatory cytokines.

Anabolic stimulation: Ntxiv nrog rau kev tswj hwm lub xeev ntawm cov ntaub so ntswg puas, cov cytokines hauv PRP kuj koom nrog cov tshuaj tiv thaiv anabolic los ntawm kev ua lawv lub luag haujlwm ntawm mitosis, tshuaj lom neeg thiab kev loj hlob.Nov yog kev kawm hauv vitro coj los ntawm Cavallo li al.Kawm txog cov teebmeem ntawm PRPs sib txawv ntawm tib neeg chondrocytes.Cov kws tshawb fawb tau pom tias PRP cov khoom uas muaj cov platelet tsawg thiab leukocyte concentrations txhawb kev ua haujlwm chondrocyte ib txwm, uas yog qhov tsim nyog los txhawb qee cov txheej txheem ntawm tes ntawm cov lus teb anabolic.Piv txwv li, kev qhia ntawm hom II collagen thiab aggregating glycans tau pom.Nyob rau hauv sib piv, siab concentrations ntawm platelets thiab leukocytes zoo li txhawb lwm yam cellular signaling txoj kev uas muaj ntau yam cytokines.Cov kws sau ntawv qhia tias qhov no yuav yog vim muaj cov qe ntshav dawb ntau hauv cov qauv PRP tshwj xeeb no.Cov hlwb no tshwm sim los ua lub luag haujlwm rau kev nthuav qhia ntawm qee yam kev loj hlob, xws li VEGF, FGF-b, thiab interleukins IL-1b thiab IL-6, uas tuaj yeem ua rau TIMP-1 thiab IL-10.Hauv lwm lo lus, piv nrog cov qauv "phem" PRP, PRP sib tov nplua nuj nyob rau hauv platelets thiab cov qe ntshav dawb zoo li txhawb cov txheeb ze invasiveness ntawm chondrocytes.

Ib txoj kev tshawb fawb tsim los ntawm Schnabel et al.tau tsim los ntsuas lub luag haujlwm ntawm autologous biomaterials hauv cov nqaij leeg nees.Cov kws sau ntawv sau cov ntshav thiab cov leeg nqaij los ntawm 6 tus neeg laus nees (hnub nyoog 2-4 xyoos), thiab tsom mus rau txoj kev tshawb fawb ntawm cov qauv qhia cov noob, DNA thiab collagen cov ntsiab lus ntawm cov leeg explants ntawm flexor digitorum superficialis ntawm nees cultured nyob rau hauv nruab nrab muaj PRP. los yog lwm yam khoom siv ntshav.Tendon explants tau coj mus rau hauv cov ntshav, ntshav, PRP, platelet deficient plasma (PPP) lossis pob txha pob txha aspirates (BMA), thiab cov amino acids tau ntxiv rau 100%, 50% lossis 10% serum dawb DMEM.Hauv kev khiav cov tshuaj biochemical uas siv tau tom qab ..., cov kws tshawb fawb tau sau tseg tias TGF- β Qhov siab ntawm PDGF-BB thiab PDGF-1 hauv PRP nruab nrab yog qhov tshwj xeeb tshaj li ntawm tag nrho lwm cov khoom siv ntshav kuaj.Tsis tas li ntawd, cov ntaub so ntswg kab lis kev cai nyob rau hauv 100% PRP nruab nrab pom tau hais tias muaj ntau cov noob qhia ntawm matrix proteins COL1A1, COL3A1 thiab COMP, tab sis tsis nce catabolic enzymes MMPs3 thiab 13. Tsawg kawg ntawm cov qauv leeg, qhov no hauv vivo txoj kev tshawb fawb txhawb kev siv cov autolo - cov khoom siv ntshav gouty, los yog PRP, rau kev kho mob ntawm cov tsiaj nyeg loj.

Chen et al.Cov txiaj ntsig rov tsim kho ntawm PRP tau tham ntxiv.Hauv lawv cov kev tshawb fawb yav dhau los, cov kws tshawb fawb tau ua pov thawj tias, ntxiv rau kev txhim kho cov pob txha mos, PRP kuj txhawb kev nce ntawm ECM synthesis thiab inhibited cov tshuaj tiv thaiv kab mob ntawm pob txha pob txha thiab nucleus pulposus.PRP tuaj yeem qhib TGF los ntawm phosphorylation ntawm Smad2 / 3- β Teeb liab txoj hauv kev ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tes thiab kev sib txawv.Tsis tas li ntawd, nws tseem ntseeg tau tias fibrin clots tsim tom qab PRP ua kom muaj cov qauv peb sab, ua kom cov hlwb ua raws, uas yuav ua rau kev tsim cov ntaub so ntswg tshiab.

Lwm cov kws tshawb fawb tau ua rau muaj txiaj ntsig zoo rau kev kho mob ntawm daim tawv nqaij ulcers nyob rau hauv daim ntawv ntawm dermatology.Qhov no kuj tseem ceeb.Piv txwv li, kev tshawb fawb los ntawm Hessler thiab Shyam hauv 2019 qhia tau hais tias PRP muaj nuj nqis raws li qhov ua tau thiab muaj txiaj ntsig zoo rau kev kho mob, thaum cov tshuaj tiv thaiv kab mob tseem ua rau muaj kev lag luam tseem ceeb rau kev kho mob.Tshwj xeeb, ntshav qab zib ko taw rwj yog qhov paub zoo txog kev noj qab haus huv, uas ua rau cov ceg tawv tau yooj yim rau kev txiav.Kev tshawb fawb luam tawm los ntawm Ahmed et al.Hauv xyoo 2017 tau pom tias autologous PRP gel tuaj yeem tsim kho qhov txhab ntawm cov neeg mob uas mob ntshav qab zib ko taw rwj los ntawm kev tso tawm qhov tsim nyog loj hlob, yog li txhim kho tus nqi kho tau zoo.Ib yam li ntawd, Gonchar thiab cov npoj yaig tau tshuaj xyuas thiab sib tham txog qhov muaj peev xwm rov tsim dua tshiab ntawm PRP thiab kev loj hlob zoo cocktails hauv kev txhim kho kev kho mob ntshav qab zib ko taw.Cov kws tshawb fawb tau hais tias kev siv cov kev loj hlob zoo sib xyaw ua ke yuav yog ib qho kev daws teeb meem, uas tuaj yeem txhim kho qhov zoo ntawm kev siv PRP thiab ib qho kev loj hlob zoo.Yog li ntawd, piv nrog rau kev siv ib qho kev loj hlob zoo, kev sib xyaw ntawm PRP thiab lwm cov tswv yim kho mob tuaj yeem txhawb kev kho mob ntawm cov kab mob ntev.

 

Fibrin

Platelets muaj ntau yam cuam tshuam nrog fibrinolytic system, uas tuaj yeem tswj hwm lossis txo qis cov tshuaj tiv thaiv fibrinolytic.Lub sij hawm kev sib raug zoo thiab kev txheeb ze ntawm cov hematological Cheebtsam thiab platelet muaj nuj nqi hauv cov hlab ntsha degradation tseem yog ib qho teeb meem tsim nyog ntawm kev sib tham dav hauv zej zog.Cov ntaub ntawv qhia txog ntau yam kev tshawb fawb uas tsuas yog tsom rau platelets, uas yog nto moo rau lawv lub peev xwm los cuam tshuam cov txheej txheem kho.Txawm hais tias muaj ntau cov kev tshawb fawb zoo, lwm yam hematological Cheebtsam, xws li coagulation factor thiab fibrinolytic systems, kuj tau pom tias yuav pab tau zoo rau kev kho qhov txhab.Los ntawm kev txhais, fibrinolysis yog ib txoj kev lom zem uas nyob ntawm kev ua kom muaj qee yam enzymes los txhawb kev degradation ntawm fibrin.Fibrinolysis cov tshuaj tiv thaiv tau raug thov los ntawm lwm tus kws sau ntawv tias cov khoom lag luam fibrin degradation (fdp) tuaj yeem yog cov tshuaj molecular lub luag haujlwm rau kev kho cov ntaub so ntswg.Cov txheej txheem tseem ceeb ntawm cov txheej txheem lom neeg ua ntej yog los ntawm fibrin deposition thiab tshem tawm ntawm angiogenesis, uas yog tsim nyog rau kev kho mob.Kev tsim cov ntshav txhaws tom qab raug mob ua haujlwm los tiv thaiv cov ntaub so ntswg los ntawm kev poob ntshav thiab kev cuam tshuam ntawm cov kab mob microbial, thiab tseem muab cov matrix ib ntus los ntawm cov hlwb tuaj yeem txav mus los thaum lub sijhawm kho.Cov hlab ntsha yog vim fibrinogen raug cleaved los ntawm serine protease, thiab platelets tau sau nyob rau hauv cross-linked fibrin fiber mesh.Cov tshuaj tiv thaiv no ua rau lub polymerization ntawm fibrin monomer, uas yog lub ntsiab tshwm sim ntawm cov ntshav txhaws.Cov hlab ntsha kuj tseem tuaj yeem siv los ua ib lub pas dej ntawm cytokines thiab kev loj hlob, uas tau tso tawm thaum lub sij hawm degranulation ntawm activated platelets.Lub fibrinolytic system yog nruj me ntsis tswj los ntawm plasmin, thiab plays lub luag hauj lwm tseem ceeb hauv kev txhawb cell migration, bioavailability ntawm kev loj hlob yam tseem ceeb thiab cov kev cai ntawm lwm yam protease systems koom nyob rau hauv cov ntaub so ntswg o thiab regeneration.Cov khoom tseem ceeb ntawm fibrinolysis, xws li urokinase plasminogen activator receptor (uPAR) thiab plasminogen activator inhibitor-1 (PAI-1), paub tias tau hais tawm hauv mesenchymal qia hlwb (MSCs), uas yog hom cell tshwj xeeb tsim nyog rau kev kho qhov txhab zoo. .

 

Cell Migration

Kev ua kom cov plasminogen los ntawm kev koom nrog uPA uPAR yog txheej txheem uas txhawb kev tsiv teb tsaws ntawm cov hlwb inflammatory vim nws txhim kho cov cellular proteolysis.Vim tsis muaj cov transmembrane thiab intracellular domains, uPAR xav tau co receptors xws li integrin thiab vitellin los tswj cov cell tsiv teb tsaws.Nws tau qhia ntxiv tias qhov kev sib txuas ntawm uPA uPAR ua rau muaj kev cuam tshuam ntawm uPAR rau vitrectonectin thiab integrin, uas txhawb nqa cell adhesion.Plasminogen activator inhibitor-1 (PAI-1) ua rau cov hlwb detach.Thaum nws khi rau uPA ntawm uPA upar integrin complex ntawm lub cell nto, nws rhuav tshem kev sib cuam tshuam ntawm upar vitellin thiab integrin vitellin.

Nyob rau hauv cov ntsiab lus ntawm cov tshuaj regenerative, cov pob txha pob txha mesenchymal qia hlwb raug mob los ntawm cov pob txha pob txha nyob rau hauv cov ntaub ntawv ntawm lub cev puas tsuaj loj heev, yog li lawv yuav pom nyob rau hauv cov kev ncig ntawm cov neeg mob uas muaj ntau yam fractures.Txawm li cas los xij, hauv cov xwm txheej tshwj xeeb, xws li lub raum tsis ua haujlwm kawg, lub siab tsis ua haujlwm kawg, lossis thaum lub sijhawm tsis lees txais tom qab hloov lub plawv, cov hlwb no yuav tsis raug kuaj pom hauv cov ntshav [66].Interestingly, cov tib neeg cov pob txha pob txha tau muab los ntawm mesenchymal (stromal) progenitor hlwb tsis tuaj yeem kuaj pom hauv cov ntshav ntawm cov neeg noj qab haus huv [67].Lub luag hauj lwm ntawm uPAR nyob rau hauv lub mobilization ntawm pob txha pob txha mesenchymal qia hlwb (BMSCs) tau npaj ua ntej, uas zoo ib yam li qhov tshwm sim ntawm uPAR nyob rau hauv lub mobilization ntawm hematopoietic qia hlwb (HSCs).Varabaneni et al.Cov txiaj ntsig tau pom tias kev siv cov granulocyte colony-stimulating factor nyob rau hauv uPAR cov nas uas tsis muaj peev xwm ua rau MSC tsis ua hauj lwm, uas ib zaug ntxiv ntxiv dag zog rau lub luag hauj lwm ntawm fibrinolysis system nyob rau hauv cell migration.Cov kev tshawb fawb ntxiv kuj tau pom tias glycosyl phosphatidylinositol anchors uPA receptors tswj adhesion, migration, proliferation thiab sib txawv los ntawm activating tej yam intracellular signaling pathways, raws li nram no: survivable phosphatidylinositol 4,5-diphosphate 3 / kiningdhase thiab pathways / kiningase. (FAK).

Hauv cov ntsiab lus ntawm MSC qhov txhab kho, fibrinolytic yam tau ua pov thawj nws qhov tseem ceeb ntxiv.Piv txwv li, cov nas uas tsis muaj plasminogen tau pom tias muaj kev ncua ntev hauv qhov txhab kho mob, qhia tias plasmin tseem ceeb hauv cov txheej txheem no.Hauv tib neeg, kev poob ntawm plasmin kuj tuaj yeem ua rau muaj teeb meem ntawm qhov txhab kho.Kev cuam tshuam ntawm cov ntshav ntws tuaj yeem cuam tshuam cov ntaub so ntswg rov tsim dua tshiab, uas tseem piav qhia tias vim li cas cov txheej txheem rov tsim dua tshiab no nyuaj rau cov neeg mob ntshav qab zib.

Cov pob txha pob txha mesenchymal qia hlwb raug xaiv mus rau qhov chaw mob kom nrawm qhov txhab kho.Nyob rau hauv cov xwm txheej ruaj khov, cov hlwb no qhia uPAuPAR thiab PAI-1.Qhov kawg ob lub proteins yog hypoxia inducible yam tseem ceeb α (HIF-1 α) Targeting yog yooj yim heev vim HIF-1 nyob rau hauv MSCs α Qhov ua rau ntawm FGF-2 thiab HGF txhawb txoj cai ntawm FGF-2 thiab HGF;HIF-2 α Nyob rau hauv lem, VEGF-A [77] yog up-regulated, uas ua ke pab rau lub qhov txhab zoo,.Tsis tas li ntawd, HGF zoo li txhim kho kev nrhiav neeg ua haujlwm ntawm cov pob txha pob txha mesenchymal qia hlwb rau hauv qhov chaw mob hauv qhov sib koom ua ke.Nws yuav tsum raug sau tseg tias cov mob ischemic thiab hypoxic tau pom tias cuam tshuam nrog kev kho qhov txhab.Txawm hais tias BMSCs zoo li nyob hauv cov ntaub so ntswg uas muab cov pa oxygen tsawg, kev ciaj sia ntawm BMSCs hauv vivo yuav raug txwv vim tias cov cell transplanted feem ntau tuag nyob rau hauv cov xwm txheej tsis zoo pom hauv cov ntaub so ntswg puas.Txoj hmoo ntawm adhesion thiab ciaj sia taus ntawm cov pob txha pob txha mesenchymal qia hlwb nyob rau hauv hypoxia nyob ntawm seb cov fibrinolytic yam secreted los ntawm cov hlwb.PAI-1 muaj affinity siab rau vitellin, yog li nws muaj peev xwm sib tw rau kev khi ntawm uPAR thiab integrin rau vitellin, yog li inhibiting cell adhesion thiab tsiv teb tsaws.

PRF

Monocyte thiab Regeneration System

Raws li cov ntaub ntawv, muaj ntau qhov kev sib tham txog lub luag haujlwm ntawm monocytes hauv kev kho qhov txhab.Macrophages feem ntau yog los ntawm cov ntshav monocytes thiab ua lub luag haujlwm tseem ceeb hauv cov tshuaj regenerative [81].Vim tias neutrophils secrete IL-4, IL-1, IL-6 thiab TNF- α, Cov hlwb no feem ntau nkag mus rau qhov txhab li 24-48 teev tom qab raug mob.Platelets tso tawm thrombin thiab platelet factor 4 (PF4), uas tuaj yeem txhawb kev nrhiav neeg ntawm monocytes thiab sib txawv rau hauv macrophages thiab dendritic hlwb.Ib qho tseem ceeb ntawm macrophages yog lawv cov yas, uas yog, lawv tuaj yeem hloov cov phenotypes thiab sib txawv rau lwm hom cell, xws li endothelial hlwb, thiab tom qab ntawd qhia cov haujlwm sib txawv rau kev sib txawv biochemical stimuli hauv qhov txhab microenvironment.Cov hlwb inflammatory qhia ob qhov loj phenotypes, M1 los yog M2, nyob ntawm seb lub zos molecular teeb liab raws li ib tug stimulation.M1 macrophages raug ntxias los ntawm cov kab mob microbial, yog li lawv muaj kev cuam tshuam ntau dua.Hauv qhov sib piv, M2 macrophages feem ntau yog tsim los ntawm hom 2 cov tshuaj tiv thaiv thiab muaj cov tshuaj tiv thaiv kab mob, feem ntau tshwm sim los ntawm kev nce hauv IL-4, IL-5, IL-9, thiab IL-13.Nws kuj tseem koom nrog kev kho cov ntaub so ntswg los ntawm kev tsim cov khoom loj hlob.Kev hloov ntawm M1 mus rau M2 subtype feem ntau yog tsav los ntawm lub sijhawm lig ntawm qhov txhab kho.M1 macrophages ua rau neutrophil apoptosis thiab pib tshem tawm cov hlwb).Lub phagocytosis ntawm neutrophils activates ib tug series ntawm cov txheej xwm, nyob rau hauv uas lub zus tau tej cov cytokines yog muab tua, polarizing macrophages thiab tso TGF- β 1. Qhov kev loj hlob ntawm no yog ib qho tseem ceeb regulator ntawm myofibroblast sib txawv thiab qhov txhab contraction, uas tso cai rau kev daws teeb meem ntawm o thiab qhov pib ntawm kev loj hlob theem hauv kev kho mob cascade [57]Lwm cov protein muaj feem cuam tshuam rau hauv cov txheej txheem ntawm tes yog serine (SG).Qhov no hemopoietic cell secretory granule proteoglycan tau pom tias tsim nyog los khaws cov proteins secretory hauv cov kab mob tiv thaiv kab mob, xws li mast cells, neutrophils thiab cytotoxic T lymphocytes.Txawm hais tias ntau lub hlwb uas tsis yog hematopoietic kuj tseem tsim cov plasminogen, tag nrho cov hlwb inflammatory tsim cov protein ntau thiab khaws cia rau hauv granules rau kev sib txuas ntxiv nrog lwm cov tshuaj kho mob, suav nrog cov proteases, cytokines, chemokines thiab loj hlob yam.Qhov tsis zoo them nqi glycosaminoglycan (GAG) chains hauv SG zoo li yog qhov tseem ceeb rau kev ruaj ntseg ntawm secretory granules, raws li lawv tuaj yeem khi rau thiab pab txhawb kev khaws cia ntawm cov khoom tseem ceeb ntawm cov khoom siv hauv cell, protein, thiab GAG saw tshwj xeeb.Hais txog lawv txoj kev koom tes hauv kev tshawb fawb PRP, Woulfe thiab cov npoj yaig tau qhia yav dhau los tias SG tsis txaus muaj feem cuam tshuam nrog kev hloov pauv ntawm platelet morphological;Platelet factor 4 β- Tsis zoo ntawm PDGF cia hauv thromboglobulin thiab platelets;Tsis zoo platelet aggregation thiab secretion hauv vitro thiab thrombosis defect hauv vivo.Cov kws tshawb fawb thiaj li xaus lus tias qhov no proteoglycan zoo li yog lub ntsiab tswj ntawm thrombosis.

Fibrinolytic

Platelet nplua nuj cov khoom tuaj yeem tau txais tus kheej tag nrho cov ntshav los ntawm kev sau thiab centrifugation, thiab faib cov khoom sib xyaw rau hauv cov txheej txheem sib txawv uas muaj cov ntshav, platelets, cov qe ntshav dawb thiab cov qe ntshav dawb.Thaum cov platelet concentration siab dua cov nqi pib, nws tuaj yeem ua kom cov pob txha loj hlob thiab cov nqaij mos, nrog rau kev phiv tsawg tshaj plaws.Daim ntawv thov ntawm autologous PRP cov khoom lag luam yog ib qho tshiab biotechnology, uas tau txuas ntxiv pom qhov ua tau zoo hauv kev txhawb nqa thiab txhim kho kev kho mob ntawm ntau yam kev raug mob.Qhov ua tau zoo ntawm txoj kev kho mob lwm txoj hauv kev no tuaj yeem raug ntaus nqi rau hauv zos xa khoom ntawm ntau yam kev loj hlob thiab cov proteins los simulate thiab txhawb nqa lub cev qhov txhab kho thiab kho cov ntaub so ntswg.Tsis tas li ntawd, fibrinolytic system pom tseeb muaj qhov tseem ceeb ntawm kev kho cov ntaub so ntswg tag nrho.Ntxiv nrog rau kev hloov pauv ntawm cov cell recruitment ntawm inflammatory cells thiab cov pob txha pob txha mesenchymal qia hlwb, nws tseem tuaj yeem tswj cov kev ua haujlwm proteolytic ntawm qhov chaw kho qhov txhab thiab cov txheej txheem rov tsim dua ntawm cov ntaub so ntswg mesodermal, suav nrog cov pob txha, pob txha thiab cov leeg, yog li nws yog ib qho tseem ceeb ntawm lub cev. tshuaj musculoskeletal.

Kev kho kom nrawm nrawm yog lub hom phiaj uas tau nrhiav los ntawm ntau tus kws tshaj lij hauv kev kho mob.PRP sawv cev rau cov cuab yeej lom neeg muaj txiaj ntsig zoo, uas txuas ntxiv muab kev cog lus kev loj hlob hauv kev txhawb nqa thiab kev sib koom tes ntawm cov xwm txheej ntawm cov txheej xwm rov ua dua tshiab.Txawm li cas los xij, vim tias cov cuab yeej kho mob no tseem nyuaj heev, tshwj xeeb tshaj yog vim nws tso tawm suav tsis txheeb bioactive yam thiab lawv cov kev sib cuam tshuam ntau yam thiab cov teeb liab cuam tshuam, xav tau kev tshawb fawb ntxiv.

(Cov ntsiab lus ntawm tsab xov xwm no tau luam tawm dua, thiab peb tsis muab ib qho kev qhia lossis kev lees paub rau qhov raug, kev ntseeg tau lossis ua tiav ntawm cov ntsiab lus muaj nyob rau hauv tsab xov xwm no, thiab tsis muaj lub luag haujlwm rau cov kev xav ntawm tsab xov xwm no, thov nkag siab.)


Post lub sij hawm: Dec-16-2022