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Generasi Berikutnya: Sel Punca Mesenkim Sebagai Sistem Penghantaran Obat Berbasis Sel
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Mesenchymal Stem Cells (MSCs) atau sel punca mesenkim merupakan sel punca dewasa yang bersifat multipoten unik yang berasal dari sumsum tulang. MSCs memiliki sifat regeneratif yang luas dan imunomodulator yang dapat digunakan dalam perbaikan jaringan dan penyembuhan luka. MSCs juga mampu bermigrasi ke tempat peradangan, lokasi jaringan yang cedera, infeksi, dan tumor dengan imunomodulasi lingkungan mikro melalui kontak sel ke sel dan pelepasan faktor terlarut sehingga memfasilitasi adanya perbaikan pada jaringan yang rusak serta merespons kemokin, sitokin, dan faktor pertumbuhan. Berkat adanya karakteristik tersebut MSCs mulai gencar dikembangkan sebagai vektor terapi gen untuk berbagai penyakit termasuk kanker, IDD, epilepsi, gangguan pendengaran sensorineural hingga stroke iskemik. Metode yang digunakan dalam artikel review ini yaitu dengan melakukan peninjauan terhadap literatur, sehingga di dapatkan 6 jurnal internasional yang diperoleh dari PubMed dan ScienceDirect yang telah memenuhi kriteria inklusi, sumber data dipublikasi paling lambat 10 tahun terakhir. Dari beberapa hasil penelitian praklinis yang dilakukan, ditemukan bahwa MSCs memiliki potensi untuk dikembangkan sebagai sistem penghantaran obat berbasis sel generasi berikutnya, yang menjanjikan dalam terapi penyakit glioblastoma, gangguan pendengaran sensorineural, kanker kolekteral, epilepsi, stroke iskemik dan Intervertebral Disc Degeneration (IDD). Namun pada pengembangannya masih ditemui adanya tantangan dalam sistem tersebut, sehingga MSCs saat ini masih memerlukan penelitian lebih lanjut agar ke depannya dapat digunakan secara optimal sebagai sistem penghantaran obat serta dapat dikembangkan secara lebih luas.
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Huleihel L, Sellares J, J C, N A, D F, R S, et al. Modified mesenchymal stem cells using miRNA transduction alter lung unjury in a bleomycin model. Am J Physiol. 2017;313:L92–103.
Skalko-Basnet N. Biologics: the role of delivery systems in improved therapy. Biol Targets Ther. 2014;4(8):107–14.
Su Y, Zhang T, Huang T, Gao J. Current advances and challenges of mesenchymal stem cells-based drug delivery system and their improvements. Int J Pharm. 2021;1–10.
Ashton S, Song Y., Nolan J, Cadogan E, Murray J, Odedra R, et al. Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutics index in vivo. Sci Transl Med. 2016;8(325):1–12.
Ayer M, Klok H. Cell-mediated delivery of synthetic nano and microparticles. J Control Release. 2017;259:92–104.
Thanuja M., Anupama C, Ranganath S. Bioengineered cellular and cell membrane-derived vehicle for actively targeted drug delivery: so near and yet so far. Adv Drug Deliv Rev. 2018;132:57–80.
Tariq I, Ali muhammad yasir, Sohail M., Amin M., Ali S, Bukhari N., et al. Lipodendriplexes mediated enhanced gene delivery: cellular to pre-clinical ivestigation. Sci Rep. 2020;10:21446.
Wang X, Gao J, Ouyang X, Wang J, Sun X, Lv Y. Mesenchymal stem cells loaded with paclitaxel-poly(lactic-co-glycolic acid) nanoparticles for glioma targeting therapy. Int J Nanomedicine. 2018;13:5231–48.
Ouyang X, Wang X, Kratz heinz bernhard, Ahmadi S, Gao J, Lv Y, et al. A trojan horse biomimetic delivery strategy using mesenchymal stem cells for PDT/PTT therapy againts lung melanoma metastasis. Biomater Sci. 2020;8:1160–70.
Krueger TE., Thorek DL., Denmeade SR, Isaacs JT, Brennen WN. Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise. 2018;651–63.
Hartono B. Sel Punca: Karakteristik, Potensi dan Aplikasinya. J Kedokt Meditek. 2016;22(60):72–5.
Sisca, Azizah N, Aldi M salas al. Potensial Mesenchymal stem cell-derived extracellular vesicles (MSC-EVS) sebagai terapi terbaru dalam iskemik retinal. Al Iqra Med J. 2018;1(2):65–73.
Fajarwati S. Hambatan mesenchymal stem cells terhadap poliferasi limfosit T. J Biosains Pascasarj. 2018;20(3):212–25.
Clavreul A, Porbaghi-Masouleh M, Roger E, Lautram N, Montero-Menei claudia N, Menei P. Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma theraphy: a good deal? J Exp Clin Cancer Res. 2017;36(135):1–11.
Stupp R, Mason W., M.J van den bent, Weller M, Fisher B, Taphoorn MJ. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.
Stupp R, Hegi ME, Mason WP, Bent MJ Van Den, Janzer robert C. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66.
Polivka J, Holubec L, Kubikova T, Priban V, Hes O, Pivovarcikova K, et al. Advances in experimental targeted therapy and immunotherapy for patients with glioblastoma multiforme. Anticancer Res. 2017;37(1):21–33.
Staedtke V, Bai R, Laterra J. Investigational new drugs for brain cancer. Expert Opin Investig Drugs. 2017;25:937–56.
Kang jennifer H. Novel chemotherapeutics and other therapies for treating high-grade glioma. Expert Opin Investig Drugs. 2015;24(10):1361–79.
Wilhelm S, Carter C, Kelley S, Lynch M, Lowinger T, Dumas J, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–44.
Carra E, Barbieri F, Marubbi D, Pattarozzi A, Favoni RE, Florio T, et al. Sorafenib selectively depletes human glioblastoma tumor-initiating cells from primary cultures. Cell Cycle. 2013;12(3):491–500.
Siegelin markus D, Raskett CM, Gilbert CA, Ross AH, Altieri DC. Sorafenib exerts anti-glioma activity in vitro and in vivo. Neurosci Lett. 2010;478(3):165–70.
Roger M, Clavreul A, Sindji L, Chassevent A, Schiller PC, Montero-Menei CN, et al. in vitro and in vivo interactions between glioma and marrow-isolated adult multilineage inducible (MIAMI) cells. Brain Res. 2012;1473:193–203.
Mangraviti A, Tzeng S, Gullotti D, Kozielski KL, Kim JE, Seng M, et al. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival. Biomaterials. 2016;100:53–6.
Balyasnikova I v, Prasol MS, Ferguson SD, Zhang L. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors. Mol Ther. 2014;22(1):140–8.
Pacioni S, Giorgio Q, Giannetti S, Morgante L, Cocce V, Bonomi A, et al. Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts. Stem Cell Resarch Ther. 2017;8(53):1–15.
Menon LG, Pratt J, Yang hong wei, M P, A G, S R. Imaging of human mesenchymal stromal cells: homing to human brain tumors. J Neurooncol. 2012;107:257–67.
Bhere D, Shah K. Stem Cell-Based Therapies for Cancer. Nat Rev Cancer. 2014;14:683–91.
Namba H, Kawaji H, Yamasaki T. Use of genetically engineered stem cells for glioma therapy. Oncol Lett. 2016;11:9–15.
Roger M, Clavreul A, Huynh N trinh, Passirani C, Schiller P, Vessieres A, et al. Ferrociphenol lipid nanocapsule delivery by mesenchymal stromal cells in brain tumor therapy. Int J Pharm. 2012;423(1):63–8.
Pacioni S, D’Alessandris Q, Giannetti S, Morgante L, De PI, Cocce V. Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic. Stem Cell Resarch Ther. 2015;6(194):1–11.
Li L, Guan Y, Liu H, Hao N, Liu T, Meng X, et al. Silica nanorattle-doxorubixicin-anchored mesenchymal stem cells for tumor-tropic therapy. ACS Nano. 2011;5:7462–70.
Clavreul A, Montagu A, Laine A-L, Tetaud C, Lautram N, Franconi F. Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules. Int J Nanomedicine. 2015;10:1259–71.
Zhang X, Yao S, Liu C, Jiang Y. Tumor tropic delivery of doxorubicin-polymer conjugates using mesenchymal stem cells for glioma therapy. Biomaterials. 2015;39:269–81.
Pessina A, Bonomi A, Cocce V, Invernici G, Navone S, Cavicchini L, et al. Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS One. 2011;6(12):e28321.
Danielyan L, Schafer R, Ameln andreas von, Buadze M, Geisler J, Klopfer T, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol. 2009;88(6):315–24.
Danielyan L, Hammer B, Stolzing A, Schafer R, Siegel G, Fabian C, et al. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Azheimer’s and Parkinson’s disease. Eur J Cell Biol. 2014;23:S123-139.
Velthoven cindy TJ Van, Kavelaars A, Bel frank Van, Heijnen CJ. Nasal administration of stem cells: a promising novel route to traet neonatal ischemic brain damage. Pediatr Res. 2010;68:419–22.
NIDCD. Cochlear implants. Bethesda, MD: National Institute of Health/National Institute on Deafness and Other Communication Disorders. 2017.
Zilberstein Y, Liberman C, Corfas G. Inner hair cells are not required for survival of spiral ganglion neurons in the adult cochlea. J Neurosci. 2012;32(2):405–10.
Liu W, Edin F, Atturo F, Rieger G, H L, P S, et al. The pre- and post-somatic segments of the human type I spiral ganglion neurons-structural and functional considerations related to cochlear implantation. Neuroscience. 2015;284:470–82.
Whitlon DS. Drug discovery for hearing loss: phenotypic screening of chemical compunds on primary cultures of the spiral ganglion. Hear Res. 2017;349:177–81.
Seyyedi M, Viana LM, Nadol JBJ. Within-subject comparison of word recognition and spiral ganglion cell count in bilateral cochlear implant recipient. Otol Neurotol. 2014;35(8):1446–50.
Leake patricia A, Stakhovskaya O, Hetherington A, Rebscher SJ, Bonham B. Effects of brain-derived neurotrophic factor (BDNF) and electrical stimulation on survival and function of cochlear spiral ganglion neurons in deafened, developing cats. J Assoc Reasearch Otolaryngol. 2013;14:187–211.
Leake patricia A, Hradek GT, Hetherington A, Stakhovskaya O. Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and functions in deafened, developing cats. J Comp Neurol. 2011;519(8):1526–45.
Scheper V, Hoffmann A, M.Gepp M, Schulz A, Hamm A, Pannier C, et al. Stem cell based drug delivery for protection of auditory neurons in a guinea pig model of cochlear implantation. Front Cellulsr Neurosci. 2019;13:177.
Prenzler NK, Salcher R, Timm M, Gaertner L, Lenarz T, Warnecke A. Intracochlear administration of steroids with a catheter during human cochlear implantation: a safety and feasibility study. Drug Deliv Transl Res. 2018;8:1191–9.
David RM, Doherty AT. Viral vectors: the road to reducing genotoxicity. Toxicol Sci. 2017;155(2):315–25.
Warnecke A, Sasse S, Wenzel GI, Hoffman A, Gross G, Paasche G, et al. Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in vitro and in vivo. Hear Res. 2012;289(1–2):86–97.
Gillespie LN, Zanin MP, Shepherd RK. Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig. J Control Release. 2015;198:26–34.
Hutten M, Dhanasingh A, Hessler R, Stover T, Esser K, Moller M, et al. In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment. PLoS One. 2014;9(8):e104564.
Zhang Y, Chen Y, Lo C, Zhuang J, Angsantikul P, Zhang Q, et al. Inhibition of pathogen adhesion by bacterial outer membrane-coated nanoparticles. Angew Chemie Int Ed. 2019;58(33):11404–8.
Parodi A, Quattrocchi N, L A, Chiappini C, Evangelopoulos M, O J, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol. 2013;8:61–8.
Piao J, Wang L, Gao F, You ye zi, Xiong Y, Yang L. Erythrocyte membrane is an alternative coating to polethylene glycol for prolonging the circulation lifetime of gold nanocages for photothermal therapy. ACS Nano. 2014;8(10):10414–25.
Chen Z, Zhao P, Luo Z, Zheng M, Tian H, Gong P, et al. Cancer cell membrane-biomimetic nanoparticles for homologous-targeting dual-modal imaging and photothermal therapy. ACS Nano. 2016;10(11):10049–57.
Wei X, Gao J, H R, T B, V A, Dehaini D, et al. Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia. Biomaterials. 2016;111:116–23.
Mirzael H, Sahebkar A, Jaafari mahmoud reza, Goodarzi M, Mirzael hamid reza. Diagnostic and therapeutic potential of exosomes in cancer: the beginning of a new tale? J Cell Physiol. 15384BC;232(12):3251–60.
Bagheri E, Abnous K, Farzad sara amel, Taghdisi seyed mohammad, Ramezani M, Alibolandi M. Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting againts colorectal cancer. Life Sci. 2020;261:118369.
Schindler C, Collinson A, Matthews C, Pointon A, Jenkinson L, R R, et al. Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. PLoS One. 2019;14(3):1–19.
Hadla M, Palazzolo S, Corona G, Caligiuri I, Canzonieri V, Toffoli G, et al. Exosome increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models. Nanomedicine. 2016;11(18):2431–41.
Alibolandi M, Abnous K, Mohammadi M, Hadizadeh F, Sadeghi F, Taghavi S, et al. Extensive preclinical investigation of polmersomal formulation of doxorubicin versus Doxil-mimic formulation. J Control Release. 2017;264:228–36.
Alvarez L, Seow Y, Yin H, Betts C, Lakhal S, J M. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341–5.
Melzer C, Rehn V, Yang Y, Bahre H, Ohe juliane Von der, Hass R. Taxol-loaded MSC-derived exosomes provide a therapeutic vehicle to target metastatic breast cancer and other carcinoma cells. Cancers (Basel). 2019;11(6):798.
Kalluri R, Lebleu VS. The biology, function and biomedical applications of exosomes. Science (80- ). 2020;367(6478):1–40.
Huang pei yu, Shih yang hsin, Tseng yi jhan, Ko tsui ling, Fu yu show, Lin yung yang. Xenograft of human umbilical mesenchymal stem cells from Wharton’s jelly as a potential therapy for rat pilocarpine-induced epilepsy. Brain, Behav an Immun. 2016;54:45–58.
Roper SN, Steindler DA. Stem cells as a potential therapy for epilepsy. Exp Neurol. 2013;244:59–66.
Cunningham M, Cho jun hyeong, Leung A, Kim kwang soo, Bolshakov vadim y, Chung S. hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell Stem Cell. 2014;15:559–73.
Hunt RF, Girskis KM, Rubenstein JL, Alvarez A, Baraban SC. GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior. Nat Neurosci. 2013;16:692–7.
Lin yu ching, Ko M. tsui ling, Shih yang hsin, Lin maan yuh anya, Fu T win, Hsiao hsiao sheng, et al. Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke. 2011;42:2045–53.
Lee H, Yun S, Kim I, Lee I, Shin jeong eun, Park soo chul, et al. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restain seizures in rat models of temporal lobe epilepsy. PLoS One. 2014;9(8):e104092.
Costa-ferro ZS., Souza BS., Leal MM., Kaneto C martins, Machado C, Campos I, et al. Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulate pro-inflammatory cytokine production in epileptic rats. Neurobiol Dis. 2012;46(2):302–13.
Huicong K, Zheng X, Furong W, Zhouping T, Feng X, Qi H, et al. The imbalanced expression of adenosine receptors in an epilepsy model corrected using targeted mesenchymal stem cell transplantation. Mol Neurobiol. 2013;48:921–30.
Leal marcus mauricio tosta, Munhoz zaquer suzana, Solano B, Machado C, Meneses T, Kaneto C martins, et al. Early transplantation of bone marrow mononuclear cells promotes neuroprotection and modulation of inflammatory after status epilepticus in mice by paracrine mechanism. Neurochem Res. 2014;39:259–68.
Chen L, Zhang G, Khan ahsan ali, Guo X, Gu Y. Clinical Efficacy and meta-analysis of stem cell therapies for patients with brain ischemia. Stem Cells Int. 2016;2016(6129579).
Kim han young, Kim tae jung, Kang L, Kim young ju, Kang min kyoung, Kim J, et al. Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke. Biomaterials. 2020;243(119942).
Zhang T, Lee yuk wai, Rui yun feng, Cheng tin yang, Jiang xiao hua, Li G. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Resarch Ther. 2013;4(70):1–15.
Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–83.
Smyth T, Kullberg M, Malik N, Smith-jones P, Graner michael w., Anchordoquy thomas j. Biodistribution and delivery efficiency of unodified tumor-derived exosomes. J Control Release. 2015;10(199):145–55.
W J, J K, J Y, D J, S C, H J, et al. Large-scale generation of cell-derived nanovesicles. Nanoscale. 2014;6(20):12056–64.
J K, L L, Y J, N L, T P, C W, et al. Biotransformations of magnetic nanoparticles in the body. Nano Today. 2016;11(3):280–4.
Gorth deborah j, Shapiro irving m, Risbund makarand v. A new understanding of the role of IL-1 in age-related intervertebral disc degeneration in a murine model. J Bone Miner Reasearch. 2019;34(8):1531–42.
Ji ming liang, Jiang H, Zhang xue jun, Shi pei liang, Li C, Wu H, et al. Preclinical development of a micro RNA-based therapy for intervertebral disc degeneration. Nat Commun. 2018;9(1):5051.
Liao Z, Li S, Lu S, Lu H, Li G, Ma L, et al. Metformin facilitates mesenchymalstem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration. Biomaterials. 2021;274(120850).
Brennan meadhbh a, Layrolle P, Mooney david j. Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration. Adv Funct Mater. 2020;30(37).
Minasian suzy varderidou, Lorenowicz magdalena j. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics. 2020;10(13):5979–97.
Liao Z, Luo R, Li G, Song Y, Zhan S, Zhao K, et al. Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect againts nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo. Theranostics. 2019;9(14):4084–100.
Xia C, Zeng Z, Fang B, Tao M, Gu C, Zheng L, et al. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radic Biol Med. 2019;143:1–15.
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