Objective: To assess the timeline dependent changes in endogenous Bone-Marrow-Mesenchymal-Stromal-Cells (BMMSC) in in-vivo chronic PD model and validating these cellular modifications in human iPSC derived MSCs of sporadic PD patients.
Background: Studies on neurodegenerative diseases like PD suggest that immune cell activation and chronic inflammation are crucial to disease onset and progression. Endogenous Bone-Marrow Mesenchymal-Stromal-Cells (BMMSCs) respond to shifts in pro- and anti-inflammatory cytokines by modulating immune cells and secreting neuroprotective factors. However, the failure of autologous BMMSC transplantation in advanced PD trials indicates impaired function in these cells under PD conditions.
Method: Protein expression in cells and tissues was evaluated through immunocytochemistry and immunohistochemistry. Basal reactive oxygen species levels were measured via H2DCFDA fluorescence with spectrophotometer. Apoptosis and proliferation were analysed by flow cytometry using Annexin-PI and Ki67 staining. Immunomodulatory and paracrine factor secretion was assessed using MLR assay and ELISA.
Results: MSC dysfunction begins early, at the premotor stage, and progressively worsens with disease advancement. Transplantation of healthy rat BMMSCs at the premotor stage effectively halted neurodegeneration, promoted neurogenesis, and mitigated inflammation. Sporadic PD patient iPSC-derived MSCs (PD-iMSCs) also showed impaired proliferation, differentiation, migration, and immunomodulatory functions, alongside elevated basal ROS levels.
Conclusion: This study is the first to show that early-stage endogenous MSC dysfunction in PD is associated with midbrain gliosis and inflammation indicating the involvement of bone marrow niche cells in the neurodegeneration observed in PD. Consequently, autologous MSC transplantation may not be beneficial for PD patients, highlighting the necessity of using allogenic MSCs from healthy individuals.
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2. Staff NP, Jones DT, Singer W. Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases. Mayo Clin Proc. 2019 May;94(5):892-905. doi: 10.1016/j.mayocp.2019.01.001. PMID: 31054608; PMCID: PMC6643282.
3. Vij R, Prossin A, Tripathy M, Kim H, Park H, Cheng T, Lotfi D, Chang D. Long-term, repeated doses of intravenous autologous mesenchymal stem cells for a patient with Parkinson’s disease: a case report. Front Neurol. 2023 Sep 27;14:1257080. doi: 10.3389/fneur.2023.1257080. PMID: 37840944; PMCID: PMC10569690.
To cite this abstract in AMA style:
R. Ghanty, I. Datta, G. Wagmare, N. Kamble, PK. Pal, V. Holla, R. Yadav, K. Mondal. Early Impairment in the Immunomodulatory Function of Mesenchymal Stromal Cells Contributes to Heightened Peripheral and Neuroinflammation in Parkinson’s Disease Insights From In Vivo Chronic PD Rat Model and In Vitro PD iPSC Model [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/early-impairment-in-the-immunomodulatory-function-of-mesenchymal-stromal-cells-contributes-to-heightened-peripheral-and-neuroinflammation-in-parkinsons-disease-insights-from-in-vivo-chronic-p/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/early-impairment-in-the-immunomodulatory-function-of-mesenchymal-stromal-cells-contributes-to-heightened-peripheral-and-neuroinflammation-in-parkinsons-disease-insights-from-in-vivo-chronic-p/