Biotechnology-based Therapy for Stroke Treatment: Review

  • Hieronimus Adiyoga Nareswara Utama Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
  • Sela Septima Mariya Center for Biomedical Research, National Research and Innovation Agency (BRIN), Cibinong Science Centre, Jalan Raya Bogor KM 46, Cibinong, West Java, Indonesia
  • Alvian Dumingan Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
  • Ratih Rinendya Putri Center for Biomedical Research, National Research and Innovation Agency (BRIN), Cibinong Science Centre, Jalan Raya Bogor KM 46, Cibinong, West Java, Indonesia
  • Sunarno Sunarno Center for Biomedical Research, National Research and Innovation Agency (BRIN), Cibinong Science Centre, Jalan Raya Bogor KM 46, Cibinong, West Java, Indonesia
  • Amarila Malik Division of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia

Abstract

Stroke is a degenerative disease that can cause a decrease in the quality of life for its survivors. Currently, various therapeutic agents have been used to treat stroke, such as antifibrinolytic, antihypertensive, statin, and antiplatelet drugs that can be given when a stroke occurs or to prevent secondary stroke attacks. However, along with the development of biotechnology and biomedical science, there is currently a lot of exploration of new stroke therapeutic agent candidates by utilizing some new signaling routes involved in stroke pathophysiology and the development of therapeutic agents developed using biotechnology methods. These therapeutic agents differ from small molecule drugs, especially in terms of their mechanism of action and manufacturing methods. This article exhibits the use of biotechnology-based therapeutic agents for stroke, including tissue plasminogen activators, therapeutic peptides, microRNA, monoclonal antibodies, and stem cells. These therapeutic agents have not only been tested on test animals but have also begun to be tested in clinical studies or have obtained marketing approval for use in ischemic stroke patients.

References

[1] T. L. Schwinghammer, J. T. DiPiro, V. L. Ellingrod, and C. V. DiPiro, Pharmacotherapy Handbook, 11th ed. New York: McGraw Hill, 2021.

[2] N. Venketasubramanian, B. W. Yoon, J. Pandian, and J. C. Navarro, “Stroke epidemiology in south, east, and south-east asia: A review,” J. Stroke, vol. 19, no. 3, pp. 286–294, 2017, doi: 10.5853/jos.2017.00234.

[3] E. S. Donkor, “Stroke in the 21st Century: A Snapshot of the Burden, Epidemiology, and Quality of Life,” Stroke Res. Treat., vol. 2018, 2018, doi: 10.1155/2018/3238165.

[4] S. Sennfält, B. Norrving, J. Petersson, and T. Ullberg, “Long-Term Survival and Function after Stroke: A Longitudinal Observational Study from the Swedish Stroke Register,” Stroke, vol. 50, no. 1, pp. 53–61, 2019, doi: 10.1161/STROKEAHA.118.022913.

[5] S. Janvier, B. De Spiegeleer, C. Vanhee, and E. Deconinck, “Falsification of biotechnology drugs: current dangers and/or future disasters?,” J. Pharm. Biomed. Anal., vol. 161, pp. 175–191, 2018, doi: 10.1016/j.jpba.2018.08.037.

[6] R. Alkahtani, “Molecular mechanisms underlying some major common risk factors of stroke,” Heliyon, vol. 8, no. 8, p. e10218, 2022, doi: 10.1016/j.heliyon.2022.e10218.

[7] D. Kuriakose and Z. Xiao, “Pathophysiology and treatment of stroke: Present status and future perspectives,” Int. J. Mol. Sci., vol. 21, no. 20, pp. 1–24, 2020, doi: 10.3390/ijms21207609.

[8] A. K. Boehme, C. Esenwa, and M. S. V. Elkind, “Stroke Risk Factors, Genetics, and Prevention,” Circ. Res., vol. 120, no. 3, pp. 472–495, 2017, doi: 10.1161/CIRCRESAHA.116.308398.

[9] C. Qin et al., “Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic
interventions,” Signal Transduct. Target. Ther., vol. 7, no. 1, 2022, doi: 10.1038/s41392-022-01064-1.

[10] Q. zhang Tuo, S. ting Zhang, and P. Lei, “Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications,” Med. Res. Rev., vol. 42, no. 1, pp. 259–305, 2022, doi: 10.1002/med.21817.

[11] Z. Shao, S. Tu, and A. Shao, “Pathophysiological mechanisms and potential therapeutic targets in
intracerebral hemorrhage,” Front. Pharmacol., vol. 10, no. September, pp. 1–8, 2019, doi: 10.3389/fphar.2019.01079.

[12] S. Lyden and J. Wold, “Acute Treatment of Ischemic Stroke,” Neurol. Clin., vol. 40, no. 1, pp. 17–32, 2022, doi: 10.1016/j.ncl.2021.08.002.

[13] American Stroke Association, “Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke,” Am. Stroke Assoc., 2019.

[14] S. M. Greenberg et al., 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association, vol. 53, no. 7. 2022. doi: 10.1161/STR.0000000000000407.

[15] C. Tremonti and M. Thieben, “Drugs in secondary stroke prevention,” Aust. Prescr., vol. 44, no. 3, pp. 85–90, 2021, doi: 10.18773/austprescr.2021.018.

[16] D. O. Kleindorfer et al., 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack; A guideline from the American Heart Association/American Stroke Association, no. July. 2021. doi:
10.1161/STR.0000000000000375.

[17] F. M. Almutairi et al., “A Review on Therapeutic Potential of Natural Phytocompounds for Stroke,” Biomedicines, vol. 10, no. 10, 2022, doi: 10.3390/biomedicines10102566.

[18] T. Tao et al., “Natural medicine in neuroprotection for ischemic stroke: Challenges and prospective,” Pharmacol. Ther., vol. 216, p. 107695, 2020, doi: 10.1016/j.pharmthera.2020.107695.

[19] M. Kesik-Brodacka, “Progress in biopharmaceutical development,” Biotechnol. Appl. Biochem., vol. 65, no.
3, pp. 306–322, 2018, doi: 10.1002/bab.1617.

[20] O. Kayser and H. Warzecha, Pharmaceutical Biotechnology: Drug Discovery and Clinical Applications, vol.
11, no. 1. Weinheim: Wiley-Blackwell, 2012. [Online]. Available: http://
link.springer.com/10.1007/978-3-319-59379-1%0Ahttp://dx.doi.org/10.1016/B978-0-12-420070-8.00002-7%0Ahttp://
dx.doi.org/10.1016/j.ab.2015.03.024%0Ahttps://doi.org/10.1080/07352689.2018.1441103%0Ahttp://www.chile.bmw-motorrad.cl/sync/showroom/lam/es/

[21] H. Almeida, M. H. Amaral, and P. Lobão, “Drugs obtained by biotechnology processing,” Brazilian J. Pharm. Sci., vol. 47, no. 2, pp. 199–207, 2011, doi: 10.1590/S1984-82502011000200002.

[22] C. Seillier et al., “Roles of the tissue-type plasminogen activator in immune response,” Cell. Immunol., vol. 371, no. January, pp. 1–8, 2022, doi: 10.1016/j.cellimm.2021.104451.

[23] B. G. Katzung, Basic and Clinical Pharmacology, 14th ed. New York: McGraw Hill, 2018.

[24] A. M. Thiebaut et al., “The role of plasminogen activators in stroke treatment: fibrinolysis and beyond,” Lancet Neurol., vol. 17, no. 12, pp. 1121–1132, 2018, doi: 10.1016/S1474-4422(18)30323-5.

[25] I. Kane and P. Sandercock, “Alteplase: Thrombolysis for acute ischemic stroke,” Therapy, vol. 2, no. 5, pp. 709–716, 2005, doi: 10.1586/14750708.2.5.709.

[26] K. R. Lees et al., “Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes: A Pooled Analysis of 9 Trials,” Stroke, vol. 47, no. 9, pp. 2373–2379, 2016, doi: 10.1161/STROKEAHA.116.013644.

[27] D. Nikitin et al., “Development and testing of thrombolytics in stroke,” J. Stroke, vol. 23, no. 1, pp. 12–36, 2021, doi: 10.5853/jos.2020.03349.

[28] E. Mohammadi, H. Seyedhosseini-Ghaheh, K. Mahnam, A. Jahanian, and H. M. M. Sadeghi, “Reteplase: Structure, Function, and Production,” Adv. Biomed. Res., pp. 1–6, 2019, doi: 10.4103/abr.abr.

[29] R. Wu, G. Chen, S. Pan, J. Zeng, and Z. Liang, “Cost-effective fibrinolytic enzyme production by Bacillus subtilis WR350 using medium supplemented with corn steep powder and sucrose,” Sci. Rep., vol. 9, no. 1, pp. 1–10, 2019, doi: 10.1038/s41598-019-43371-8.

[30] C. Wu, C. Zheng, J. Wang, and P. Jiang, “Recombinant expression of thrombolytic agent reteplase in marine microalga tetraselmis subcordiformis (Chlorodendrales, chlorophyta),” Mar. Drugs, vol. 19, no. 6, 2021, doi: 10.3390/md19060315.

[31] T. Ma, Z. Li, and S. Wang, “Production of Bioactive Recombinant Reteplase by Virus-Based Transient Expression System in Nicotiana benthamiana,” Front. Plant Sci., vol. 10, no. October, pp. 1–11, 2019, doi: 10.3389/fpls.2019.01225.

[32] S. Padmanabhan, N. Mandi, K. R. Sundaram, S. K. Tandra, and S. Bandyopadhyay, “Asn 12 and Asn 278: Critical residues for in vitro biological activity of reteplase,” Adv. Hematol., vol. 2010, 2010, doi: 10.1155/2010/172484.

[33] J. Mican, M. Toul, D. Bednar, and J. Damborsky, “Structural Biology and Protein Engineering of Thrombolytics,” Comput. Struct. Biotechnol. J., vol. 17, pp. 917–938, 2019, doi: 10.1016/j.csbj.2019.06.023.

[34] S. B. Coutts, E. Berge, B. C. V. Campbell, K. W. Muir, and M. W. Parsons, “Tenecteplase for the treatment of
acute ischemic stroke: A review of completed and ongoing randomized controlled trials,” Int. J. Stroke, vol. 13, no. 9, pp. 885–892, 2018, doi: 10.1177/1747493018790024.

[35] S. J. Warach, A. N. Dula, and T. J. Milling, “Tenecteplase Thrombolysis for Acute Ischemic Stroke,” Stroke, vol. 51, no. 11, pp. 3440–3451, 2020, doi: 10.1161/STROKEAHA.120.029749.

[36] S. Li, H. Q. Gu, H. Dai, G. Lu, and Y. Wang, “Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE): Rationale and design of a multicentre, prospective, randomised, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial,” Stroke Vasc. Neurol., pp. 1–6, 2024, doi: 10.1136/svn-2023-003035.

[37] J. L. Lau and M. K. Dunn, “Therapeutic peptides: Historical perspectives, current development trends, and future directions,” Bioorganic Med. Chem., vol. 26, no. 10, pp. 2700–2707, 2018, doi: 10.1016/j.bmc.2017.06.052.

[38] U. Anand, A. Bandyopadhyay, N. K. Jha, J. M. Pérez de la Lastra, and A. Dey, “Translational aspect in peptide drug discovery and development: An emerging therapeutic candidate,” BioFactors, vol. 49, no. 2, pp. 251–269, 2023, doi: 10.1002/biof.1913.

[39] A. C. L. Lee, J. L. Harris, K. K. Khanna, and J. H. Hong, “A comprehensive review on current advances in peptide drug development and design,” Int. J. Mol. Sci., vol. 20, no. 10, pp. 1–21, 2019, doi: 10.3390/ijms20102383.

[40] Y. Ge, W. Chen, P. Axerio-Cilies, and Y. T. Wang, “NMDARs in Cell Survival and Death: Implications in Stroke Pathogenesis and Treatment,” Trends Mol. Med., vol. 26, no. 6, pp. 533–551, 2020, doi: 10.1016/j.molmed.2020.03.001.

[41] Q. J. Wu and M. Tymianski, “Targeting nmda receptors in stroke: New hope in neuroprotection Tim Bliss,” Mol. Brain, vol. 11, no. 1, pp. 1–14, 2018, doi: 10.1186/s13041-018-0357-8.

[42] B. Ballarin and M. Tymianski, “Discovery and development of NA-1 for the treatment of acute ischemic stroke,” Acta Pharmacol. Sin., vol. 39, no. 5, pp. 661–668, 2018, doi: 10.1038/aps.2018.5.

[43] M. D. Hill et al., “Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial,” Lancet, vol. 395, no. 10227, pp. 878–887, 2020, doi: 10.1016/S0140-6736(20)30258-0.

[44] S. Zhang et al., “Critical role of increased PTEN nuclear translocation in excitotoxic and ischemic neuronal injuries,” J. Neurosci., vol. 33, no. 18, pp. 7997–8008, 2013, doi: 10.1523/JNEUROSCI.5661-12.2013.

[45] Z. Wang et al., “First-in-human safety, tolerability, and pharmacokinetics of SY-007, a prolonged action neuroprotective drug for ischemic stroke, in healthy Chinese subjects,” Eur. J. Pharm. Sci., vol. 170, p. 106104, 2022, doi: 10.1016/j.ejps.2021.106104.

[46] S. Paul, A. C. Nairn, P. Wang, and P. J. Lombroso, “NMDA-mediated activation of the tyrosine phosphatase STEP regulates the duration of ERK signaling,” Nat. Neurosci., vol. 6, no. 1, pp. 34–42, 2003, doi: 10.1038/nn989.

[47] S. Rajagopal, R. Poddar, and S. Paul, “Tyrosine phosphatase STEP is a key regulator of glutamate-induced prostaglandin E2 release from neurons,” J. Biol. Chem., vol. 297, no. 2, p. 100944, 2021, doi: 10.1016/j.jbc.2021.100944.

[48] I. Deb et al., “Neuroprotective role of a brain-enriched tyrosine phosphatase, STEP, in focal cerebral ischemia,” J. Neurosci., vol. 33, no. 45, pp. 17814–17826, 2013, doi: 10.1523/JNEUROSCI.2346-12.2013.

[49] S. Mukherjee, R. Poddar, I. Deb, and S. Paul, “Dephosphorylation of specific sites in the KIS domain leads to ubiquitin-mediated degradation of the tyrosine phosphatase STEP,” Biochem. J., vol. 440, no. 1, pp. 115–125, 2011, doi: 10.1042/BJ20110240.

[50] R. Poddar, S. Rajagopal, L. Winter, A. M. Allan, and S. Paul, “A peptide mimetic of tyrosine phosphatase STEP as a potential therapeutic agent for treatment of cerebral ischemic stroke,” J. Cereb. Blood Flow Metab., vol. 39, no. 6, pp. 1069–1084, 2019, doi: 10.1177/0271678X17747193.

[51] H. Lv, J. Li, and Y. Che, “miR-31 from adipose stem cell-derived extracellular vesicles promotes recovery of neurological function after ischemic stroke by inhibiting TRAF6 and IRF5,” Exp. Neurol., vol. 342, no. 4, p. 113611, 2021, doi: 10.1016/j.expneurol.2021.113611.

[52] T. Zheng et al., “MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway,” Biomed. Pharmacother., vol. 117, no. April, p. 109117, 2019, doi: 10.1016/j.biopha.2019.109117.

[53] Y. Ji et al., “An MMP-9 exclusive neutralizing antibody attenuates blood-brain barrier breakdown in mice with stroke and reduces stroke patient-derived MMP-9 activity,” Pharmacol. Res., vol. 190, no. December 2022, p.
106720, 2023, doi: 10.1016/j.phrs.2023.106720.

[54] S. Bodhankar et al., “PD-L1 monoclonal antibody treats ischemic stroke by controlling central nervous system inflammation,” Stroke, vol. 46, no. 10, pp. 2926–2934, 2015, doi: 10.1161/STROKEAHA.115.010592.

[55] S. Bodhankar, Y. Chen, A. A. Vandenbark, S. J. Murphy, and H. Offner, “PD-L1 enhances CNS inflammation and infarct volume following experimental stroke in mice in opposition to PD-1,” J. Neuroinflammation, vol. 10, pp. 1–15, 2013, doi: 10.1186/1742-2094-10-111.

[56] S. Bodhankar, Y. Chen, A. Lapato, A. A. Vandenbark, S. J. Murphy, and H. Offner, “Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy in stroke,” Front. Cell. Neurosci., vol. 8, no. August, pp. 1–14, 2014, doi: 10.3389/fncel.2014.00228.

[57] N. Hassani, S. Taurin, and S. Alshammary, “Meta-Analysis: The Clinical Application of Autologous Adult Stem Cells in the Treatment of Stroke,” Stem Cells Cloning Adv. Appl., vol. 14, pp. 81–91, 2021, doi: 10.2147/SCCAA.S344943.

[58] M. L. Levy, J. R. Crawford, N. Dib, L. Verkh, N. Tankovich, and S. C. Cramer, “Phase I/II study of safety and preliminary efficacy of intravenous allogeneic mesenchymal stem cells in chronic stroke,” Stroke, vol. 50, no. 10, pp. 2835–2841, 2019, doi: 10.1161/STROKEAHA.119.026318.

[59] G. K. Steinberg et al., “Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: A phase 1/2a study,” Stroke, vol. 47, no. 7, pp. 1817–1824, 2016, doi: 10.1161/
STROKEAHA.116.012995.

[60] K. Houkin et al., “Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial,” JAMA Neurol., vol. 81, no. 2, pp. 154–162, 2024, doi: 10.1001/jamaneurol.2023.5200.

[61] A. Asgari Taei, L. Dargahi, P. Khodabakhsh, M. Kadivar, and M. Farahmandfar, “Hippocampal neuroprotection mediated by secretome of human mesenchymal stem cells against experimental stroke,” CNS Neurosci. Ther., vol. 28, no. 9, pp. 1425–1438, 2022, doi: 10.1111/cns.13886.

[62] H. J. Hur et al., “Conditioned Medium of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Exerts
Neurorestorative Effects against Ischemic Stroke Model,” Int. J. Mol. Sci., vol. 23, no. 14, 2022, doi: 10.3390/ijms23147787.

[63] D. Salikhova et al., “Therapeutic effects of hipsc-derived glial and neuronal progenitor cells-conditioned medium in experimental ischemic stroke in rats,” Int. J. Mol. Sci., vol. 22, no. 9, 2021, doi: 10.3390/ijms22094694.

[64] A. Gupta, J. L. Andresen, R. S. Manan, and R. Langer, “Nucleic acid delivery for therapeutic applications,” Adv. Drug Deliv. Rev., vol. 178, p. 113834, 2021, doi: 10.1016/j.addr.2021.113834.

[65] J. O’Brien, H. Hayder, Y. Zayed, and C. Peng, “Overview of microRNA biogenesis, mechanisms of actions, and circulation,” Front. Endocrinol. (Lausanne)., vol. 9, no. AUG, pp. 1–12, 2018, doi: 10.3389/fendo.2018.00402.

[66] A. A. Seyhan, “Trials and Tribulations of MicroRNA Therapeutics,” Int. J. Mol. Sci., vol. 25, no. 3, pp. 1–41, 2024, doi: 10.3390/ijms25031469.

[67] F. Jin and J. Xing, “Circulating miR-126 and miR-130a levels correlate with lower disease risk, disease severity, and reduced inflammatory cytokine levels in acute ischemic stroke patients,” Neurol. Sci., vol. 39, no. 10, pp. 1757–1765, 2018, doi: 10.1007/s10072-018-3499-7.

[68] P. Liu et al., “Upregulation of MicroRNA-128 in the Peripheral Blood of Acute Ischemic Stroke Patients is Correlated with Stroke Severity Partially through Inhibition of Neuronal Cell Cycle Reentry,” Cell Transplant., vol. 28, no. 7, pp. 839–850, 2019, doi: 10.1177/0963689719846848.

[69] G. Mao, P. Ren, G. Wang, F. Yan, and Y. Zhang, “MicroRNA-128-3p Protects Mouse Against Cerebral Ischemia Through Reducing p38α Mitogen-Activated Protein Kinase Activity,” J. Mol. Neurosci., vol. 61, no. 2, pp. 152–158, 2017, doi: 10.1007/s12031-016-0871-z.

[70] W. Zhang et al., “MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex,” Elife, vol. 5, no. FEBRUARY2016, pp. 1–22, 2016, doi: 10.7554/eLife.11324.

[71] M. Y. Momin, R. R. Gaddam, M. Kravitz, A. Gupta, and A. Vikram, “The challenges and opportunities in the development of microrna therapeutics: A multidisciplinary viewpoint,” Cells, vol. 10, no. 11, 2021, doi: 10.3390/cells10113097.

[72] Z. Zhang, Y. W. Qin, G. Brewer, and Q. Jing, “MicroRNA degradation and turnover: Regulating the regulators,” Wiley Interdiscip. Rev. RNA, vol. 3, no. 4, pp. 593–600, 2012, doi: 10.1002/wrna.1114.

[73] I. Dasgupta and A. Chatterjee, “Recent advances in miRNA delivery systems,” Methods Protoc., vol. 4, no. 1, pp. 1–18, 2021, doi: 10.3390/mps4010010.

[74] S. Ghafouri-Fard et al., “Nanoparticle-mediated delivery of microRNAs-based therapies for treatment of disorders,” Pathol. Res. Pract., vol. 248, p. 154667, 2023, doi: 10.1016/j.prp.2023.154667.

[75] G. Houen, “Therapeutic Antibodies: An Overview,” Methods Mol. Biol., vol. 2313, pp. 1–25, 2022, doi: 10.1007/978-1-0716-1450-1_1.

[76] P. J. Carter and A. Rajpal, “Designing antibodies as therapeutics,” Cell, vol. 185, no. 15, pp. 2789–2805, 2022, doi: 10.1016/j.cell.2022.05.029.

[77] M. Suzuki, C. Kato, and A. Kato, “Therapeutic antibodies: Their mechanisms of action and the pathological findings they induce in toxicity studies,” J. Toxicol. Pathol., vol. 28, no. 3, pp. 133–139, 2015, doi: 10.1293/tox.2015-0031.

[78] D. Woods, Q. Jiang, and X. Chu, “Monoclonal antibody as an emerging therapy for acute ischemic stroke,” Int. J. Physiol. Pathophysiol. Pharmacol., vol. 12, no. 4, pp. 95–106, 2020.

[79] S. Singh, S. Saleem, and G. L. Reed, “Alpha2-Antiplasmin: The Devil You Don’t Know in Cerebrovascular and Cardiovascular Disease,” Front. Cardiovasc. Med., vol. 7, no. December, pp. 1–10, 2020, doi: 10.3389/fcvm.2020.608899.

[80] G. L. Reed, A. K. Houng, S. Singh, and D. Wang, “α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke,” Semin. Thromb. Hemost., vol. 43, no. 2, pp. 191–199, 2017, doi: 10.1055/s-0036-1585077.

[81] G. L. Reed, G. R. Matsueda, and E. Haber, “Synergistic fibrinolysis: Combined effects of plasminogen activators and an antibody that inhibits α2-antiplasmin,” Proc. Natl. Acad. Sci. U. S. A., vol. 87, no. 3, pp. 1114–1118, 1990, doi: 10.1073/pnas.87.3.1114.

[82] G. L. Reed, “Functional characterization of monoclonal antibody inhibitors of α2- antiplasmin that accelerate fibrinolysis in different animal plasmas,” Hybridoma, vol. 16, no. 3, pp. 281–286, 1997, doi: 10.1089/hyb.1997.16.281.

[83] S. J. Humphreys, C. S. Whyte, and N. J. Mutch, “‘Super’ SERPINs—A stabilizing force against fibrinolysis in thromboinflammatory conditions,” Front. Cardiovasc. Med., vol. 10, no. April, pp. 1–12, 2023, doi: 10.3389/fcvm.2023.1146833.

[84] T. Lopez et al., “Functional selection of protease inhibitory antibodies,” Proc. Natl. Acad. Sci. U. S. A., vol. 116, no. 33, pp. 16314–16319, 2019, doi: 10.1073/pnas.1903330116.

[85] J. M. Sun et al., “Advances in Antibody-Based Therapeutics for Cerebral Ischemia,” Pharmaceutics, vol. 15, no. 1, pp. 1–27, 2023, doi: 10.3390/pharmaceutics15010145.

[86] S. Poliwoda et al., “Stem cells: a comprehensive review of origins and emerging clinical roles in medical practice,” Orthop. Rev. (Pavia)., vol. 14, no. 3, 2022, doi: 10.52965/001C.37498.

[87] A. Can, “A concise review on the classification and nomenclature of stem cells,” Turkish J. Hematol., vol. 25, no. 2, pp. 57–59, 2008.

[88] A. Casado-Díaz, “Stem Cells in Regenerative Medicine,” J. Clin. Med., vol. 11, no. 18, 2022, doi: 10.3390/jcm11185460.

[89] R. M. Aly, “Current state of stem cell-based therapies: An overview,” Stem Cell Investig., vol. 7, no. May, pp. 1–10, 2020, doi: 10.21037/sci-2020-001.

[90] D. M. Hoang et al., “Stem cell-based therapy for human diseases,” Signal Transduct. Target. Ther., vol. 7, no. 1, 2022, doi: 10.1038/s41392-022-01134-4.

[91] E. Sekerdag, I. Solaroglu, and Y. Gursoy-Ozdemir, “Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options,” Curr. Neuropharmacol., vol. 16, no. 9, pp. 1396–1415, 2018, doi: 10.2174/1570159x16666180302115544.

[92] S. Yaqubi and M. Karimian, “Stem cell therapy as a promising approach for ischemic stroke treatment,” Curr. Res. Pharmacol. Drug Discov., vol. 6, no. April, p. 100183, 2024, doi: 10.1016/j.crphar.2024.100183.

[93] L. Hovhannisyan, S. Khachatryan, A. Khamperyan, and S. Matinyan, “A review and meta-analysis of stem cell therapies in stroke patients: effectiveness and safety evaluation,” Neurol. Sci., vol. 45, no. 1, pp. 65–74, 2024, doi: 10.1007/s10072-023-07032-z.

[94] T. M. Osborn, P. J. Hallett, J. M. Schumacher, and O. Isacson, “Advantages and Recent Developments of Autologous Cell Therapy for Parkinson’s Disease Patients,” Front. Cell. Neurosci., vol. 14, no. April, pp. 1–13, 2020, doi: 10.3389/fncel.2020.00058.

[95] A. Musiał-Wysocka, M. Kot, and M. Majka, “The Pros and Cons of Mesenchymal Stem Cell-Based Therapies,” Cell Transplant., vol. 28, no. 7, pp. 801–812, 2019, doi: 10.1177/0963689719837897.

[96] A. Asgari Taei, P. Khodabakhsh, S. Nasoohi, M. Farahmandfar, and L. Dargahi, “Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges,” Mol. Neurobiol., vol. 59, no. 10, pp. 6281–6306, 2022, doi: 10.1007/s12035-022-02967-4.

[97] M. Gnecchi et al., “Paracrine Action Accounts for Marked Protection of Ischemic Heart by Akt-modified Mesenchymal Stem Cells,” Nature, vol. 11, no. 4, pp. 367–368, 2005, doi: 10.1096/fj.04-2702fje.

[98] B. Chouaib, M. Haack-Sørensen, F. Chaubron, F. Cuisinier, and P. Y. Collart-Dutilleul, “Towards the Standardization of Mesenchymal Stem Cell Secretome-Derived Product Manufacturing for Tissue Regeneration,” Int. J. Mol. Sci., vol. 24, no. 16, pp. 0–15, 2023, doi: 10.3390/ijms241612594.

[99] J. A. Pawitan, “Prospect of stem cell conditioned medium in regenerative medicine,” Biomed Res. Int., vol. 2014, pp. 7–9, 2014, doi: 10.1155/2014/965849.
Published
2024-10-31
How to Cite
UTAMA, Hieronimus Adiyoga Nareswara et al. Biotechnology-based Therapy for Stroke Treatment: Review. JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 22, n. 2, p. 248-260, oct. 2024. ISSN 2614-6495. Available at: <http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/1613>. Date accessed: 05 nov. 2024. doi: https://doi.org/10.35814/jifi.v22i2.1613.