Genetically engineered mesenchymal stem cells with dopamine synthesis for Parkinson’s disease in animal models

Abstract

Although striatal delivery of three critical genes for dopamine synthesis by viruses is a potential clinical approach for treating Parkinson’s disease (PD), the approach makes it difficult to finely control dopamine secretion amounts and brings safety concerns. Here, we generate genetically engineered mesenchymal stem cells encoding three critical genes for dopamine synthesis (DOPA-MSCs). DOPA-MSCs retain their MSC identity and stable ability to secrete dopamine during passaging. Following transplantation, DOPA-MSCs reinstate striatal dopamine levels and correct motor function in PD rats. Importantly, after grafting into the caudate and putamen, DOPA-MSCs provide homotopic reconstruction of midbrain dopamine pathways by restoring striatal dopamine levels, and safely and long-term (up to 51 months) correct motor disorders and nonmotor deficits in acute and chronic PD rhesus monkey models of PD even with advanced PD symptoms. The long-term benefits and safety results support the idea that the development of dopamine-synthesized engineered cell transplantation is an important strategy for treating PD.

Chemotactic Micro/Nanomotors for Biomedical Applications

“…This is because PD essentially originates from inflammation. Li et al [65] developed genetically engineered dopamine-producing MSCs (DOPA-MSCs) over an eight-year period for PD treatment. Due to the complex pathogenesis and significant inter-individual variation in PD patients, a single animal model does not reflect well the broad effectiveness of cell transplantation.…”

“…Reproduced with permission. [65] Copyright 2022, The Author(s). Similar to MSCs, neural stem cells (NSCs) can similarly migrate to hypoxic tumor and inflammatory sites, secreting MCP-1 and HGF/VEGF.…”

“…For example, Joseph et al [105] report a fully synthetic organic nanosystem that is designed by encapsulating glucose oxidase (GOx) alone or in combination with per-oxidase into nanoscale and biocompatible asymmetric polymeric vesicles (called polymersomes). in an in vitro model validated the chemotaxis of polymersomes to glucose and the ability to cross the BBB in vitro, and explained that the observed chemotaxis was due to the enhanced advective diffusion and redirection of ID Salmonella S. typhimurium Breast cancer [30] EM@MSNs-loaded neutrophil Neutrophils / [34] NPNs Breast cancer [35] BSA NPs Acute lung Injury [36] PTX-CL-NEs Glioblastoma [38] UM-NEs (Ag-UK) Thrombus [39] Neutrobots Spongioblastoma [40] NM-NPs-CFZ Circulating tumor cells [41] PD-1-MM@PLGA/RAPA Macrophages Glioblastoma [45] PLGA-DTX-Fe 3 O 4 Cancer cells [46] MMDM Breast cancer [47] MΦ-CA-MNPs/ MΦ-DOX-TSLPs Breast cancer [48] CAP@M Lung cancer [49] MA-Lip Breast cancer [50] MZ@PNM@GCP Periodontitis [51] DOX-HCl-Loaded Sperms Sperm cells Cancer cells [54] FSFSM Cancer cells [55] SN-DOX Stem cells Breast cancer [61] PLGA-MSCs Lung cancer [62] Glycoengineered MSCs Lung cancer [63] HGF-eMSCs Myocardial infarction [64] DOPA-MSCs Parkinson's disease [65] Cos@C-bMSCs Middle cerebral artery [66] NSCs Occlusion [67] MSN-DOX-NSCs Glioblastoma [68] Glioblastoma Tn-S-CPMV T cells Breast cancer [72] TNPs Periodontitis [73] PLGA-aAPC/anti-PD-1 Melanoma [74] CTL-NP-aP Breast cancer [75] EN-TCR Epidermal cancer [76] DOX-platelets Platelets Lymphoma [78] P-aPDL-1 Circulating tumor cells [83] PNPs Coronary restenosis…”

Organic Functional Group on Carbon Nanotube Modulates the Maturation of SH‐SY5Y Neuronal Models

“…Various cell lines have been used to help get new insights on neurological processes and regeneration through neuronal models. [4][5][6][7] Among the most common ones, neuroblastoma cells (SH-SY5Y) can be easily differentiated into mature neurons upon neurotoxic treatments and, thus, widely used as models for neurodegenerative disorders. [8] To design neuro-promoting substrates and understand their effect on neuronal networks, the synaptic processes is key for neuronal cell growth, maturation, and proper functions.…”

“…Various cell lines have been used to help get new insights on neurological processes and regeneration through neuronal models. [ 4–7 ] Among the most common ones, neuroblastoma cells (SH‐SY5Y) can be easily differentiated into mature neurons upon neurotoxic treatments and, thus, widely used as models for neurodegenerative disorders. [ 8 ]…”