Document Type : Review Article
Author
Build Goal Health, Inc Ceo & Founder, Los Angles, California, United States
Abstract
A number of animal disease models have been created in the past to investigate the molecular basis of neurological diseases and identify novel treatments, but their effectiveness has been limited by the absence of comparable animal models. There are still several important problems that need to be overcome, including the high expenses associated with creating animal models, ethical issues, and a lack of similarity to human disease. More than 90% of medications fail in the last stage of the human clinical trial as a result of inadequate early screening and assessment of the molecules. A novel strategy based on induced pluripotent stem cells has been developed to get around these restrictions (iPSCs). A new road map for clinical translational research and regeneration treatment has been made possible by the discovery of iPSCs. In this paper, we investigate the potential use of patient-derived iPSCs to neurological disorders as well as their significance in scientific and clinical studies for the creation of disease models and a road map for the next of medicine. The role of human iPSCs in the most prevalent neurodegenerative illnesses (such as Parkinson’s and Alzheimer’s disease, diabetic neuropathy) was evaluated. The patient-on-a-chip idea, where iPSCs may be cultivated on 3D matrices within microfluidic devices to produce an in vitro disease model for tailored medication, is another new development in the field of personalized medicine that we looked into.
Keywords
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2.Pandey, Shashank, et al. “iPSCs in Neurodegenerative Disorders: A Unique Platform for Clinical Research and Personalized Medicine.” Journal of Personalized Medicine 12.9 (2022): 1485.
3.Lin, Xiying, Jiayu Tang, and Yan-Ru Lou. “Human pluripotent stem-cell-derived models as a missing link in drug discovery and development.” Pharmaceuticals 14.6 (2021): 525.
4.Omole, Adekunle Ebenezer, and Adegbenro Omotuyi John Fakoya. “Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.” PeerJ 6 (2018): e4370.
5.Cummings, Jeffrey L., et al. “The costs of developing treatments for Alzheimer’s disease: A retrospective exploration.” Alzheimer’s & Dementia 18.3 (2022): 469-477.
6.Takahashi, Kazutoshi, and Shinya Yamanaka. “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.” cell 126.4 (2006): 663-676.
7.Ghajari, Ghazal, Arefe Heydari, and Masoud Ghorbani. “Mesenchymal stem cell-based therapy and female infertility: limitations and advances.” Current Stem Cell Research & Therapy (2022).
8.Omole, Adekunle Ebenezer, and Adegbenro Omotuyi John Fakoya. “Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.” PeerJ 6 (2018): e4370.
9.Mullard, Asher. “Stem-cell discovery platforms yield first clinical candidates: Induced pluripotent stem cell-derived’disease-in-a-dish’models have propelled neurological drugs from Bristol-Myers Squibb, GlaxoSmithKline and Roche into clinical trials.” Nature Reviews Drug Discovery 14.9 (2015): 589-592.
10.Sugai, Keiko, et al. “Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.” Molecular brain 9 (2016): 1-15.
11.Hockemeyer, Dirk, and Rudolf Jaenisch. “Induced pluripotent stem cells meet genome editing.” Cell stem cell 18.5 (2016): 573-586.
12.Cosset, Erika, et al. “Generation of human induced pluripotent stem cell line UNIGEi003-A from skin fibroblasts of an apparently healthy male donor.” Stem cell research 48 (2020): 101928.
13.Chlebanowska, Paula, et al. “Origin of the induced pluripotent stem cells affects their differentiation into dopaminergic neurons.” International journal of molecular sciences 21.16 (2020): 5705.
14.Zhang, Lin, et al. “Establishment of two induced pluripotent stem cell line from healthy elderly (IPTi005-A and IPTi007-A).” Stem Cell Research 45 (2020): 101808.
15.Tello, Judith A., et al. “Animal models of neurodegenerative disease: Recent advances in fly highlight innovative approaches to drug discovery.” Frontiers in molecular neuroscience 15 (2022).
16.Dawson, Ted M., Todd E. Golde, and Clotilde Lagier-Tourenne. “Animal models of neurodegenerative diseases.” Nature neuroscience 21.10 (2018): 1370-1379.
17.Jucker, Mathias. “The benefits and limitations of animal models for translational research in neurodegenerative diseases.” Nature medicine 16.11 (2010): 1210-1214.
18.Colpo, Gabriela D., et al. “Animal models for the study of human neurodegenerative diseases.” Animal Models for the Study of Human Disease. Academic Press, 2017. 1109-1129.
19.Li, Li, Jianfei Chao, and Yanhong Shi. “Modeling neurological diseases using iPSC-derived neural cells: iPSC modeling of neurological diseases.” Cell and tissue research 371 (2018): 143-151.
20.Hu, Xinchao, et al. “Modeling Parkinson’s disease using induced pluripotent stem cells.” Stem Cells International 2020 (2020).
21.Kalia, Lorraine V., and Anthony E. Lang. “Parkinson’s disease.” The Lancet 386.9996 (2015): 896-912.
22.Cobb, Melanie M., et al. “iPS cells in the study of PD molecular pathogenesis.” Cell and tissue research 373 (2018): 61-77.
23.Wang, Yanlin, et al. “Generation of induced pluripotent stem cell line (ZZUi007-A) from a 52-year-old patient with a novel CHCHD2 gene mutation in Parkinson’s disease.” Stem Cell Research 32 (2018): 87-90.
24.Takahashi, Kazutoshi, et al. “Induction of pluripotent stem cells from adult human fibroblasts by defined factors.” cell 131.5 (2007): 861-872.
25.Suda, Yukari, et al. “Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson’s disease-like motor dysfunction.” Molecular brain 11 (2018): 1-9.
26.Shiba-Fukushima, Kahori, et al. “Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease.” Human molecular genetics 26.16 (2017): 3172-3185.
27.Schweitzer, Jeffrey S., et al. “Personalized iPSC-derived dopamine progenitor cells for Parkinson’s disease.” New England Journal of Medicine 382.20 (2020): 1926-1932.
28.Chen, Zhi-ting, et al. “Generation of an induced pluripotent stem cell line, FJMUUHi001-A, from a hereditary Parkinson’s disease patient with homozygous mutation of c. 189dupA in PARK7.” Stem Cell Research 51 (2021): 102175.
29.Ferri, Cleusa P., et al. “Global prevalence of dementia: a Delphi consensus study.” The lancet 366.9503 (2005): 2112-2117.
30.Liu, Xin-Yu, Lin-Po Yang, and Lan Zhao. “Stem cell therapy for Alzheimer’s disease.” World Journal of Stem Cells 12.8 (2020): 787.
31.Cooper, Oliver, et al. “Differentiation of human ES and Parkinson’s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid.” Molecular and Cellular Neuroscience 45.3 (2010): 258-266.
32.Nicholas, Cory R., et al. “Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development.” Cell stem cell 12.5 (2013): 573-586.
33.Peitz, Michael, et al. “Blood-derived integration-free iPS cell line UKBi011-A from a diagnosed male Alzheimer’s disease patient with APOE ɛ4/ɛ4 genotype.” Stem cell research 29 (2018): 250-253.
34.Liu, Sijun, et al. “Reconstruction of Alzheimer’s disease cell model in vitro via extracted peripheral blood molecular cells from a sporadic patient.” Stem Cells International 2020 (2020).
35.Zhang, Lin, et al. “Generation of induced pluripotent stem cell line (IPTi002-A) from an 87-year old sporadic Alzheimer’s disease patient with APOE3 (ε3/ε3) genotype.” Stem Cell Research 53 (2021): 102282.
36.Arber, Charles, et al. “Familial Alzheimer’s disease patient-derived neurons reveal distinct mutation-specific effects on amyloid beta.” Molecular Psychiatry 25.11 (2020): 2919-2931.
37.Tolosa, Laia, Eugenia Pareja, and Maria José Gómez-Lechón. “Clinical application of pluripotent stem cells: an alternative cell-based therapy for treating liver diseases?.” Transplantation 100.12 (2016): 2548-2557.
38.Liu, Dongwei, et al. “Concise review: current trends on applications of stem cells in diabetic nephropathy.” Cell Death & Disease 11.11 (2020): 1000.
39.Agrawal, Akriti, et al. “Recent advances in the generation of β-cells from induced pluripotent stem cells as a potential cure for diabetes mellitus.” Cell Biology and Translational Medicine, Volume 14: Stem Cells in Lineage Specific Differentiation and Disease (2021): 1-27.
40.Hostetter, Thomas H. “Prevention of end-stage renal disease due to type 2 diabetes.” New England Journal of Medicine 345.12 (2001): 910-912.
41.Wang, Qian, et al. “The effect of Schwann cells/Schwann cell-like cells on cell therapy for peripheral neuropathy.” Frontiers in Cellular Neuroscience 16 (2022).
42.Himeno, Tatsuhito, et al. “Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem cells ameliorate diabetic polyneuropathy in mice.” BioMed research international 2013 (2013).
43.Song, Bi, et al. “The directed differentiation of human iPS cells into kidney podocytes.” (2012): e46453.
44.Lam, Albert Q., et al. “Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers.” Journal of the American Society of Nephrology 25.6 (2014): 1211-1225.
45.Namer, Barbara, et al. “Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors.” EBioMedicine 39 (2019): 401-408.
46.Hamazaki, Takashi, et al. “Concise review: induced pluripotent stem cell research in the era of precision medicine.” Stem Cells 35.3 (2017): 545-550.
47.Chun, Yong Soon, Kyunghee Byun, and Bonghee Lee. “Induced pluripotent stem cells and personalized medicine: current progress and future perspectives.” Anatomy & cell biology 44.4 (2011): 245-255.
48.Russo, Fabiele B et al. “Induced pluripotent stem cells for modeling neurological disorders.” World journal of transplantation vol. 5,4 (2015): 209-21.
49.Ebert, Allison D., et al. “Induced pluripotent stem cells from a spinal muscular atrophy patient.” Nature 457.7227 (2009): 277-280.
50.Stoddard-Bennett, Theo, and Renee Reijo Pera. “Treatment of Parkinson’s disease through personalized medicine and induced pluripotent stem cells.” Cells 8.1 (2019): 26.
51.Ghajari, Ghazal, Arefe Heydari, and Masoud Ghorbani. “Mesenchymal stem cell-based therapy and female infertility: limitations and advances.” Current Stem Cell Research & Therapy (2022).
52.Logan, Sarah et al. “Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models.” Comprehensive Physiology vol. 9,2 565-611. 14 Mar. 2019.
53.Ebert, Antje D., Ping Liang, and Joseph C. Wu. “Induced pluripotent stem cells as a disease modeling and drug screening platform.” Journal of cardiovascular pharmacology 60.4 (2012): 408-416.
54.Yang, Jiayin, et al. “Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome.” Journal of Biological Chemistry 285.51 (2010): 40303-40311.
55.Yin, Fangchao, et al. “HiPSC-derived multi-organoids-on-chip system for safety assessment of antidepressant drugs.” Lab on a Chip 21.3 (2021): 571-581.
56.Perestrelo, Ana Rubina, et al. “Microfluidic organ/body-on-a-chip devices at the convergence of biology and microengineering.” Sensors 15.12 (2015): 31142-31170.
57.Imamura, Yoshinori, et al. “Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer.” Oncology reports 33.4 (2015): 1837-1843.
58.Workman, Michael J., et al. “Enhanced utilization of induced pluripotent stem cell–derived human intestinal organoids using microengineered chips.” Cellular and molecular gastroenterology and hepatology 5.4 (2018): 669-677.
59.Wang, Yaqing, et al. “In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system.” Lab on a Chip 18.23 (2018): 3606-3616.
60.Musah, Samira, et al. “Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.” Nature biomedical engineering 1.5 (2017): 0069.
61.Kujala, Ville J., et al. “Laminar ventricular myocardium on a microelectrode array-based chip.” Journal of Materials Chemistry B 4.20 (2016): 3534-3543.
62.Brown, Jacquelyn A., et al. “Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit.” Journal of neuroinflammation 13.1 (2016): 1-17.
63.Brown, Jacquelyn A., et al. “Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor.” Biomicrofluidics 9.5 (2015): 054124.
64.Sakolish, Courtney, et al. “Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS).” Toxicology 448 (2021): 152651.
65.Fanizza, Francesca, et al. “Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders.” Journal of Tissue Engineering 13 (2022): 20417314221095339.
66.Zhao, Jing, et al. “APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids.” Nature communications 11.1 (2020): 5540.
67.Arber, Charles, et al. “Familial Alzheimer’s disease mutations in PSEN1 lead to premature human stem cell neurogenesis.” Cell reports 34.2 (2021): 108615.
68.Raja, Waseem K., et al. “Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer’s disease phenotypes.” PloS one 11.9 (2016): e0161969.
69.Kim, Hongwon, et al. “Modeling G2019S-LRRK2 sporadic Parkinson’s disease in 3D midbrain organoids.” Stem Cell Reports 12.3 (2019): 518-531.
70.Hernández-Sapiéns, Mercedes A., et al. “A three-dimensional Alzheimer’s disease cell culture model using iPSC-derived neurons carrying A246E mutation in PSEN1.” Frontiers in Cellular Neuroscience 14 (2020): 151.
71.Rouleau, Nicolas, et al. “A Long‐Living Bioengineered Neural Tissue Platform to Study Neurodegeneration.” Macromolecular bioscience 20.3 (2020): 2000004.
72.Chen, Mei, et al. “Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients.” Journal of proteomics 182 (2018): 21-33.
2.Pandey, Shashank, et al. “iPSCs in Neurodegenerative Disorders: A Unique Platform for Clinical Research and Personalized Medicine.” Journal of Personalized Medicine 12.9 (2022): 1485.
3.Lin, Xiying, Jiayu Tang, and Yan-Ru Lou. “Human pluripotent stem-cell-derived models as a missing link in drug discovery and development.” Pharmaceuticals 14.6 (2021): 525.
4.Omole, Adekunle Ebenezer, and Adegbenro Omotuyi John Fakoya. “Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.” PeerJ 6 (2018): e4370.
5.Cummings, Jeffrey L., et al. “The costs of developing treatments for Alzheimer’s disease: A retrospective exploration.” Alzheimer’s & Dementia 18.3 (2022): 469-477.
6.Takahashi, Kazutoshi, and Shinya Yamanaka. “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.” cell 126.4 (2006): 663-676.
7.Ghajari, Ghazal, Arefe Heydari, and Masoud Ghorbani. “Mesenchymal stem cell-based therapy and female infertility: limitations and advances.” Current Stem Cell Research & Therapy (2022).
8.Omole, Adekunle Ebenezer, and Adegbenro Omotuyi John Fakoya. “Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.” PeerJ 6 (2018): e4370.
9.Mullard, Asher. “Stem-cell discovery platforms yield first clinical candidates: Induced pluripotent stem cell-derived’disease-in-a-dish’models have propelled neurological drugs from Bristol-Myers Squibb, GlaxoSmithKline and Roche into clinical trials.” Nature Reviews Drug Discovery 14.9 (2015): 589-592.
10.Sugai, Keiko, et al. “Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.” Molecular brain 9 (2016): 1-15.
11.Hockemeyer, Dirk, and Rudolf Jaenisch. “Induced pluripotent stem cells meet genome editing.” Cell stem cell 18.5 (2016): 573-586.
12.Cosset, Erika, et al. “Generation of human induced pluripotent stem cell line UNIGEi003-A from skin fibroblasts of an apparently healthy male donor.” Stem cell research 48 (2020): 101928.
13.Chlebanowska, Paula, et al. “Origin of the induced pluripotent stem cells affects their differentiation into dopaminergic neurons.” International journal of molecular sciences 21.16 (2020): 5705.
14.Zhang, Lin, et al. “Establishment of two induced pluripotent stem cell line from healthy elderly (IPTi005-A and IPTi007-A).” Stem Cell Research 45 (2020): 101808.
15.Tello, Judith A., et al. “Animal models of neurodegenerative disease: Recent advances in fly highlight innovative approaches to drug discovery.” Frontiers in molecular neuroscience 15 (2022).
16.Dawson, Ted M., Todd E. Golde, and Clotilde Lagier-Tourenne. “Animal models of neurodegenerative diseases.” Nature neuroscience 21.10 (2018): 1370-1379.
17.Jucker, Mathias. “The benefits and limitations of animal models for translational research in neurodegenerative diseases.” Nature medicine 16.11 (2010): 1210-1214.
18.Colpo, Gabriela D., et al. “Animal models for the study of human neurodegenerative diseases.” Animal Models for the Study of Human Disease. Academic Press, 2017. 1109-1129.
19.Li, Li, Jianfei Chao, and Yanhong Shi. “Modeling neurological diseases using iPSC-derived neural cells: iPSC modeling of neurological diseases.” Cell and tissue research 371 (2018): 143-151.
20.Hu, Xinchao, et al. “Modeling Parkinson’s disease using induced pluripotent stem cells.” Stem Cells International 2020 (2020).
21.Kalia, Lorraine V., and Anthony E. Lang. “Parkinson’s disease.” The Lancet 386.9996 (2015): 896-912.
22.Cobb, Melanie M., et al. “iPS cells in the study of PD molecular pathogenesis.” Cell and tissue research 373 (2018): 61-77.
23.Wang, Yanlin, et al. “Generation of induced pluripotent stem cell line (ZZUi007-A) from a 52-year-old patient with a novel CHCHD2 gene mutation in Parkinson’s disease.” Stem Cell Research 32 (2018): 87-90.
24.Takahashi, Kazutoshi, et al. “Induction of pluripotent stem cells from adult human fibroblasts by defined factors.” cell 131.5 (2007): 861-872.
25.Suda, Yukari, et al. “Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson’s disease-like motor dysfunction.” Molecular brain 11 (2018): 1-9.
26.Shiba-Fukushima, Kahori, et al. “Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease.” Human molecular genetics 26.16 (2017): 3172-3185.
27.Schweitzer, Jeffrey S., et al. “Personalized iPSC-derived dopamine progenitor cells for Parkinson’s disease.” New England Journal of Medicine 382.20 (2020): 1926-1932.
28.Chen, Zhi-ting, et al. “Generation of an induced pluripotent stem cell line, FJMUUHi001-A, from a hereditary Parkinson’s disease patient with homozygous mutation of c. 189dupA in PARK7.” Stem Cell Research 51 (2021): 102175.
29.Ferri, Cleusa P., et al. “Global prevalence of dementia: a Delphi consensus study.” The lancet 366.9503 (2005): 2112-2117.
30.Liu, Xin-Yu, Lin-Po Yang, and Lan Zhao. “Stem cell therapy for Alzheimer’s disease.” World Journal of Stem Cells 12.8 (2020): 787.
31.Cooper, Oliver, et al. “Differentiation of human ES and Parkinson’s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid.” Molecular and Cellular Neuroscience 45.3 (2010): 258-266.
32.Nicholas, Cory R., et al. “Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development.” Cell stem cell 12.5 (2013): 573-586.
33.Peitz, Michael, et al. “Blood-derived integration-free iPS cell line UKBi011-A from a diagnosed male Alzheimer’s disease patient with APOE ɛ4/ɛ4 genotype.” Stem cell research 29 (2018): 250-253.
34.Liu, Sijun, et al. “Reconstruction of Alzheimer’s disease cell model in vitro via extracted peripheral blood molecular cells from a sporadic patient.” Stem Cells International 2020 (2020).
35.Zhang, Lin, et al. “Generation of induced pluripotent stem cell line (IPTi002-A) from an 87-year old sporadic Alzheimer’s disease patient with APOE3 (ε3/ε3) genotype.” Stem Cell Research 53 (2021): 102282.
36.Arber, Charles, et al. “Familial Alzheimer’s disease patient-derived neurons reveal distinct mutation-specific effects on amyloid beta.” Molecular Psychiatry 25.11 (2020): 2919-2931.
37.Tolosa, Laia, Eugenia Pareja, and Maria José Gómez-Lechón. “Clinical application of pluripotent stem cells: an alternative cell-based therapy for treating liver diseases?.” Transplantation 100.12 (2016): 2548-2557.
38.Liu, Dongwei, et al. “Concise review: current trends on applications of stem cells in diabetic nephropathy.” Cell Death & Disease 11.11 (2020): 1000.
39.Agrawal, Akriti, et al. “Recent advances in the generation of β-cells from induced pluripotent stem cells as a potential cure for diabetes mellitus.” Cell Biology and Translational Medicine, Volume 14: Stem Cells in Lineage Specific Differentiation and Disease (2021): 1-27.
40.Hostetter, Thomas H. “Prevention of end-stage renal disease due to type 2 diabetes.” New England Journal of Medicine 345.12 (2001): 910-912.
41.Wang, Qian, et al. “The effect of Schwann cells/Schwann cell-like cells on cell therapy for peripheral neuropathy.” Frontiers in Cellular Neuroscience 16 (2022).
42.Himeno, Tatsuhito, et al. “Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem cells ameliorate diabetic polyneuropathy in mice.” BioMed research international 2013 (2013).
43.Song, Bi, et al. “The directed differentiation of human iPS cells into kidney podocytes.” (2012): e46453.
44.Lam, Albert Q., et al. “Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers.” Journal of the American Society of Nephrology 25.6 (2014): 1211-1225.
45.Namer, Barbara, et al. “Pain relief in a neuropathy patient by lacosamide: Proof of principle of clinical translation from patient-specific iPS cell-derived nociceptors.” EBioMedicine 39 (2019): 401-408.
46.Hamazaki, Takashi, et al. “Concise review: induced pluripotent stem cell research in the era of precision medicine.” Stem Cells 35.3 (2017): 545-550.
47.Chun, Yong Soon, Kyunghee Byun, and Bonghee Lee. “Induced pluripotent stem cells and personalized medicine: current progress and future perspectives.” Anatomy & cell biology 44.4 (2011): 245-255.
48.Russo, Fabiele B et al. “Induced pluripotent stem cells for modeling neurological disorders.” World journal of transplantation vol. 5,4 (2015): 209-21.
49.Ebert, Allison D., et al. “Induced pluripotent stem cells from a spinal muscular atrophy patient.” Nature 457.7227 (2009): 277-280.
50.Stoddard-Bennett, Theo, and Renee Reijo Pera. “Treatment of Parkinson’s disease through personalized medicine and induced pluripotent stem cells.” Cells 8.1 (2019): 26.
51.Ghajari, Ghazal, Arefe Heydari, and Masoud Ghorbani. “Mesenchymal stem cell-based therapy and female infertility: limitations and advances.” Current Stem Cell Research & Therapy (2022).
52.Logan, Sarah et al. “Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models.” Comprehensive Physiology vol. 9,2 565-611. 14 Mar. 2019.
53.Ebert, Antje D., Ping Liang, and Joseph C. Wu. “Induced pluripotent stem cells as a disease modeling and drug screening platform.” Journal of cardiovascular pharmacology 60.4 (2012): 408-416.
54.Yang, Jiayin, et al. “Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome.” Journal of Biological Chemistry 285.51 (2010): 40303-40311.
55.Yin, Fangchao, et al. “HiPSC-derived multi-organoids-on-chip system for safety assessment of antidepressant drugs.” Lab on a Chip 21.3 (2021): 571-581.
56.Perestrelo, Ana Rubina, et al. “Microfluidic organ/body-on-a-chip devices at the convergence of biology and microengineering.” Sensors 15.12 (2015): 31142-31170.
57.Imamura, Yoshinori, et al. “Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer.” Oncology reports 33.4 (2015): 1837-1843.
58.Workman, Michael J., et al. “Enhanced utilization of induced pluripotent stem cell–derived human intestinal organoids using microengineered chips.” Cellular and molecular gastroenterology and hepatology 5.4 (2018): 669-677.
59.Wang, Yaqing, et al. “In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system.” Lab on a Chip 18.23 (2018): 3606-3616.
60.Musah, Samira, et al. “Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.” Nature biomedical engineering 1.5 (2017): 0069.
61.Kujala, Ville J., et al. “Laminar ventricular myocardium on a microelectrode array-based chip.” Journal of Materials Chemistry B 4.20 (2016): 3534-3543.
62.Brown, Jacquelyn A., et al. “Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit.” Journal of neuroinflammation 13.1 (2016): 1-17.
63.Brown, Jacquelyn A., et al. “Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor.” Biomicrofluidics 9.5 (2015): 054124.
64.Sakolish, Courtney, et al. “Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS).” Toxicology 448 (2021): 152651.
65.Fanizza, Francesca, et al. “Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders.” Journal of Tissue Engineering 13 (2022): 20417314221095339.
66.Zhao, Jing, et al. “APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids.” Nature communications 11.1 (2020): 5540.
67.Arber, Charles, et al. “Familial Alzheimer’s disease mutations in PSEN1 lead to premature human stem cell neurogenesis.” Cell reports 34.2 (2021): 108615.
68.Raja, Waseem K., et al. “Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer’s disease phenotypes.” PloS one 11.9 (2016): e0161969.
69.Kim, Hongwon, et al. “Modeling G2019S-LRRK2 sporadic Parkinson’s disease in 3D midbrain organoids.” Stem Cell Reports 12.3 (2019): 518-531.
70.Hernández-Sapiéns, Mercedes A., et al. “A three-dimensional Alzheimer’s disease cell culture model using iPSC-derived neurons carrying A246E mutation in PSEN1.” Frontiers in Cellular Neuroscience 14 (2020): 151.
71.Rouleau, Nicolas, et al. “A Long‐Living Bioengineered Neural Tissue Platform to Study Neurodegeneration.” Macromolecular bioscience 20.3 (2020): 2000004.
72.Chen, Mei, et al. “Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients.” Journal of proteomics 182 (2018): 21-33.
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