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This is mainly due to the lack of effective human PD models. To address this, we generated an in\u00a0vitro PD model using Wharton's jelly\u2010derived mesenchymal stem cells (WJMSCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WJMSCs were isolated from the umbilical cord using an enzymatic method. MSCs were characterized by RT\u2010PCR, immunofluorescence, and trilineage differentiation. MSCs were differentiated into dopaminergic neuron\u2010like cells (DAN) and further degenerated by treating them with either MPP+ iodide or the A53T mutated \u03b1\u2010synuclein variant. Gene expression analysis by qRT\u2010PCR and protein analysis by immunofluorescence, flow cytometry, and ELISA were performed. Assays to measure LDH, ROS, NO, GSH, and mitochondrial membrane potential were also performed after degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WJMSCs were positive for MSC markers and were able to differentiate into adipocytes, chondrocytes, and osteocytes. DAN obtained after the differentiation of WJMSCs for 48\u2009h expressed neuronal markers such as synapsin 1, neuropilin, neurofilament, and MAPT along with dopaminergic markers such as Nurr1, DAT, TH, DDC, and KCNJ6 and were functionally active. Upon degeneration of DAN by MPP+ or A53T, elevated levels of SNCA and downregulation of TH, Nurr1, DAT, and KCNJ6 were observed. Furthermore, increased expression of \u03b1\u2010SYN was detected at the protein level as well. Finally, reduction in mitochondrial membrane potential and GSH levels along with an increase in intracellular ROS, nitrite production, and LDH levels confirmed that the in\u00a0vitro PD\u2010like model exhibited the molecular characteristics of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This model is rapid, cost\u2010efficient, and effective for understanding the molecular mechanisms of the disease and can also be used for screening of emerging therapeutics for PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70299","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T05:27:52Z","timestamp":1745299672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of In\u00a0Vitro Parkinson's Disease Model Mediated by\n                    <scp>MPP<\/scp>\n                    + and \u03b1\u2010Synuclein Using Wharton's Jelly Mesenchymal Stem Cells"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2871-9565","authenticated-orcid":false,"given":"Naisarg","family":"Gamit","sequence":"first","affiliation":[{"name":"Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine Manipal Academy of Higher Education (MAHE)  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-8671","authenticated-orcid":false,"given":"Manasi","family":"Patil","sequence":"additional","affiliation":[{"name":"Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine Manipal Academy of Higher Education (MAHE)  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0864-7728","authenticated-orcid":false,"given":"B. S.","family":"Soumya","sequence":"additional","affiliation":[{"name":"Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine Manipal Academy of Higher Education (MAHE)  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6715-6005","authenticated-orcid":false,"given":"Arun","family":"Dharmarajan","sequence":"additional","affiliation":[{"name":"School of Human Sciences The University of Western Australia  Nedlands Western Australia Australia"},{"name":"Curtin Medical School Curtin University  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3787-5647","authenticated-orcid":false,"given":"Sudha","family":"Warrier","sequence":"additional","affiliation":[{"name":"Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine Manipal Academy of Higher Education (MAHE)  Bangalore India"},{"name":"Department of Biotechnology, Faculty of Biomedical Sciences and Technology Sri Ramachandra Institute of Higher Education and Research  Chennai India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60492-X"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113472"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00328"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/NS20210026"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0212"},{"issue":"23","key":"e_1_2_11_10_1","first-page":"1987","article-title":"Human Umbilical Cord Wharton's Jelly\u2010Derived Mesenchymal Stem Cells Differentiation Into Nerve\u2010Like Cells","volume":"118","author":"Ma L.","year":"2005","journal-title":"Chinese Medical Journal"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/14653249.2011.579957"},{"key":"e_1_2_11_12_1","first-page":"217","article-title":"Understanding Pathophysiology of Sporadic Parkinson's Disease in Drosophila Model: Potential Opportunities and Notable Limitations In: Challenges in Parkinson's Disease","author":"Modi P.","year":"2016","journal-title":"IntechOpen"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.94"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-106"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10795"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25421"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23894"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.877545"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.78.23"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.2.3.484"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-015-0039-8"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.034"},{"key":"e_1_2_11_24_1","first-page":"59","volume-title":"What Causes the Death of Dopaminergic Neurons in Parkinson's Disease?","author":"Surmeier D. 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