Kuwunika kwa Chitetezo ndi Kuchita bwino kwa Neurotrophic factor therapy mu Ischemic Stroke

Cerebral stroke, yomwe imadziwikanso kuti "stroke" kapena "cerebrovascular accident" (CVA), ndi matenda oopsa a cerebrovascular omwe amadziwika ndi kuphulika kwadzidzidzi kwa mitsempha muubongo kapena kutsekeka kwa magazi kupita ku ubongo, zomwe zimapangitsa kuwonongeka kwa minofu yaubongo. Zimaphatikizapo zikwapu zonse za ischemic ndi hemorrhagic. Stroke ndi yachiwiri yomwe imayambitsa imfa padziko lonse lapansi, yomwe ili ndi chiwerengero chachikulu cha imfa ndi olumala mwa akuluakulu.

Ischemic Stroke (IS) imatanthawuza kukomoka kwa ischemic necrosis kapena kufewetsa kwa minofu ya muubongo chifukwa cha kusokonezeka kwa kayendedwe ka ubongo, ischemia, ndi hypoxia. Chifukwa cha kuchuluka kwake, kuchuluka kwa anthu, kufa, komanso kulumala, chakhala chimodzi mwazinthu zazikulu zomwe zikubweretsa matenda padziko lonse lapansi. Malinga ndi ziwerengero, pafupifupi anthu 15 miliyoni padziko lonse lapansi amadwala sitiroko ya ischemic chaka chilichonse, pomwe 5 miliyoni amafa ndi 5 miliyoni omwe ali ndi olumala kwakanthawi.

The Mechanism of Stem Cell Therapy for Ischemic Stroke

Maselo a Mesenchymal Stem Cells (MSCs) ndi mtundu wa maselo amtundu wambiri omwe amatha kudzipatula kumagulu osiyanasiyana, kuphatikizapo mafupa, adipose, ndi magazi a umbilical. Chifukwa cha kuchuluka kwawo, amatha kusiyanitsa ma osteoblasts, chondrocytes, adipocytes, ngakhale ma neurons. Pakadali pano, kupatsirana kwa MSC kwawoneka ngati njira yatsopano yochizira matenda a ischemic, kuphatikiza sitiroko, matenda amtsempha yamagazi, komanso matenda amtsempha wamagazi. Kafukufuku wambiri awonetsa kuti mphamvu yabwino kwambiri ya neuroprotective ya MSC ndi chinthu chofunikira kwambiri pochiza ischemic stroke.

Malipoti aposachedwa akuwonetsa kuti MSC imalimbikitsa makamaka kukonza kuwonongeka kwa minofu ya neural, kubwezeretsanso magwiridwe antchito a minyewa, kuchepetsa kukula kwa cerebral infarction, ndikulimbikitsa neurogenesis ndi angiogenesis kudzera mu paracrine zotsatira, immunomodulatory effects, ndi anti-apoptotic effect, motero kuchita gawo lachirengedwe. mu ischemic stroke.

Paracrine zotsatira

Ma paracrine a MSC, kuphatikiza ma exosomes ndi ma vesicles akunja, ndi omwe amathandizira kwambiri pakuchiritsa kwawo. M'dera la kuvulala kwa ubongo, MSCs ikhoza kuwonetsa zinthu zosiyanasiyana za kukula, kuphatikizapo ubongo-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), fibroblast yoyambirira. kukula factor (bFGF), glial cell-derived neurotrophic factor, ndi hepatocyte kukula factor, pakati pa ena. Zinthuzi zimathandizira kuchepetsa gawo la cerebral infarction ndikubwezeretsanso ntchito ya neural, potero kumapangitsa kuvulala kwa ubongo.

Mphamvu ya immunomodulatory

Kafukufuku wapeza kuti MSCs imakhalanso ndi ntchito ziwiri zoyendetsera chitetezo chapakati pa chitetezo chamthupi pambuyo pa sitiroko: Kumbali imodzi, amatha kuonjezera kwambiri chiwerengero cha maselo a B, ma cell a NK, ndi maselo a T mu minofu ya ubongo, zomwe zimapangitsa kuti chitetezo cha mthupi chitetezeke. Kumbali ina, kuchuluka kwa zinthu zotupa kumatha kuyambitsa ntchito ya immunosuppressive ya MSCs, potero kumapangitsa kuti pakhale zoletsa ziwiri pakuchulukira kwa ma lymphocyte komanso kupanga zinthu zotupa, zomwe zimapangitsa anti-inflammatory phenotype.

Kuwongolera kwa cell apoptosis

Cell apoptosis ndi njira yofunikira yakuvulala kwa neuronal mu sitiroko ya ischemic, ndipo ma MSC amatha kuletsa neuronal apoptosis, kukhala ndi zotsatira za neuroprotective. Thandizo la MSC limathanso kuchepetsa ischemic stroke-induced astrocyte necrosis, komanso, ma MSC omwe ali ndi hypoxia-preconditioned amawonetsa zotsatira zabwino zochiritsira zochepetsera ma cell necrosis oyambitsidwa ndi kukha magazi muubongo.

Kuwunika kwachipatala kwa stem cell therapy ya ischemic stroke.

Kusintha kwa maselo amtundu wa mesenchymal stem (MSCs) pochiza sitiroko ya ischemic kwawonetsa zotsatira zabwino m'maphunziro a preclinical. Ochita kafukufuku adachita kafukufuku wa mayeso achipatala a 20 okhudzana ndi odwala 1127, kuphatikizapo 573 mu gulu loyesera (lomwe linachitidwa ndi MSCs) ndi 554 mu gulu lolamulira (mankhwala ochiritsira). Poyerekeza ndi mankhwala ochiritsira, kupatsirana kwa MSC kunachepetsa kwambiri chiwerengero cha National Institutes of Health Stroke Scale (NIHSS) pa 1, 3, miyezi 6, ndi chaka chimodzi pambuyo pa chithandizo. Zinathandiziranso kwambiri ntchito za index ya moyo watsiku ndi tsiku pa miyezi 1 ndi 6, komanso magwiridwe antchito agalimoto komanso kuchuluka kwaodziyimira pawokha pa 1, 3, ndi 6 miyezi.

Zizindikiro zazikulu zowunikira zikuphatikizapo: (1) National Institutes of Health Stroke Scale (NIHSS); (2) Barthel Index (BI); (3) Chigoli cha Fugl-Meyer Assessment (FMA); (4) Ntchito Yodziyimira payokha (FIM) chiwerengero; ndi (5) Modified Rankin Scale (mRS) mphambu.

Poyerekeza ndi mankhwala ochiritsira, chithandizo cha mesenchymal stem cell (MSC) cha stroke chimachepetsa kwambiri chiwerengero cha NIH Stroke Scale (NIHSS) pa miyezi ya 3.

Poyerekeza ndi mankhwala ochiritsira, panalibe kusiyana kwakukulu mu chiwerengero cha Barthel Index (BI) pa miyezi ya 3 ndi mesenchymal stem cell (MSC) mankhwala a stroke.

Poyerekeza ndi mankhwala ochiritsira, chithandizo cha mesenchymal stem cell (MSC) cha stroke chinathandiza kwambiri chiwerengero cha Functional Movement Assessment (FMA) pa miyezi ya 3.

Poyerekeza ndi mankhwala ochiritsira, chithandizo cha mesenchymal stem cell (MSC) cha stroke chinathandiza kwambiri chiwerengero cha Functional Independence Measure (FIM) pa miyezi ya 3.

Poyerekeza ndi mankhwala ochiritsira, chithandizo cha mesenchymal stem cell (MSC) cha sitiroko sichinasonyeze kusiyana kwakukulu mu chiwerengero cha Modified Rankin Scale (mRS) pa miyezi ya 3.

Kuphatikizidwa pamodzi, gulu lalikulu la maphunziro a preclinical likuwonetsa kuthekera ndi mphamvu ya mesenchymal stem cell (MSC) transplantation therapy pochiza sitiroko ya ischemic, yomwe pamlingo wina imathandizira kuperewera kwa minyewa, kuyendetsa bwino kwa magalimoto, ndi zochitika za tsiku ndi tsiku kwa odwala omwe ali ndi ischemic. sitiroko.

Tsogolo ndi Zoyembekeza

M'zaka zaposachedwa, kuchokera pakusiyanitsa kosavuta ndikusintha kuzindikira kwa kafukufuku wa stem cell mpaka kukuya kosalekeza ndi kukulitsa njira zosiyanasiyana za kafukufuku wa MSC, kutukuka kwa gawo la kafukufuku wama cell cell kwakula komanso kwatsopano. Pakadali pano, kuyesa kwa nyama sikungotsimikizira zotsatira zochiritsira zama cell tsinde, komanso kuthekera kwa chithandizo cha MSC cha sitiroko ya ischemic kwaperekedwa. M'mayesero ambiri azachipatala, chithandizo cha MSC cha sitiroko ya ischemic chikupita patsogolo.

Posachedwapa, pakhala pali mayesero achipatala okwana 101 omwe adalembetsedwa mu database ya US Clinical trial for stem cell therapy for stroke, ndi maphunziro 25 okhudzana ndi chithandizo cha MSC cha ischemic stroke. Mayesero azachipatala awonetsa kuti ma MSC ali ndi kusintha kwakukulu muubongo kwa odwala omwe ali ndi ischemic stroke, kutsimikizira mphamvu zawo komanso chitetezo chanthawi yayitali.

M'tsogolomu, padzakhala zopambana zambiri zachipatala zomwe zikuphatikizapo MSCs zomwe zidzamasuliridwe ku ntchito zachipatala, zomwe zikuthandizira makampani azachipatala komanso kuteteza thanzi ndi moyo wa anthu padziko lonse lapansi.