Volume 10,Issue 4
A Neuroprotective Microenvironment was Constructed for Dopaminergic Neuron Grafts Using Autologous Treg Cells
Objective: To discuss the construction of a neuroprotective microenvironment using autologous regulatory T cells (Treg cells), in order to improve the transplantation survival rate and functional recovery effect of dopaminergic neurons derived from induced pluripotent stem cells (iPSCs) in Parkinson's disease (PD) models. Methods: We have elaborated in detail on the current research on animal models of PD: the combined transplantation of autologous regulatory T cells and dopaminergic (DA) neurons derived from induced pluripotent stem cells. Result: Co-transplantation of Treg cells can significantly increase the survival rate of dopaminergic neuron grafts, inhibit the host immune response and microglial cell activation, and promote the recovery of motor function in model animals. Treg cells activate the Rac1/Akt signaling pathway through direct cell contact (such as CD47-SIRPA interaction), and secrete anti-inflammatory factors (such as IL-10, TGF-β) and neurotrophic factors, exerting immunomodulatory and direct neuroprotective effects. Drug enhancement of Treg function can further optimize this protective effect. Conclusion: I have elaborated in detail on the current research status and clinical feasibility of using autologous regulatory T cells to construct a neuroprotective microenvironment for dopamine neurons transplantation. At the same time, we envisioned the future treatment methods for PD, providing new ideas for research and treatment for PD scholars and doctors.
[1] Dauer W, Przedborski S., 2003, Parkinson's Disease: Mechanisms and Models. Neuron, 39(6): 889-909.
[2] Maheshwari S, Akram H, Bulstride H, et al., 2024, Dopaminergic Cell Replacement for Parkinson's Disease: Addressing the Intracranial Delivery Hurdle. J Parkinsons Dis, 14(3): 415-435.
[3] Kikuchi T, Morizane A, Doi D, et al., 2017, Human iPS Cell-derived Dopaminergic Neurons Function in a Primate Parkinson's Disease Model. Nature, 548(7669): 592-596.
[4] Ferrari CC, Tarelli R, 2011, Parkinson's Disease and Systemic Inflammation. Parkinsons Dis, 2011: 436813.
[5] Hu W, Li J, Cheng X, 2023, Regulatory T Cells and Cardiovascular Diseases. Chin Med J (Engl), 136(23): 2812-2823.
[6] Park TY, Jeon J, Lee N, et al., 2023, Co-transplantation of Autologous T(reg) cells in a Cell Therapy for Parkinson's Disease. Nature, 619(7970): 606-615.
[7] Huang Y, Liu Z, Cao B, et al., 2017, Treg Cells Protect Dopaminergic Neurons against MPP+ Neurotoxicity via CD47-SIRPA Interaction. Cell Physiol Biochem, 41(3): 1240-1254.
[8] Huang Y, Liu Z, Cao B, et al., 2020, Treg Cells Attenuate Neuroinflammation and Protect Neurons in a Mouse Model of Parkinson's Disease. J Neuroimmune Pharmacol, 15(2): 224-237.
[9] Lewkowicz N, Klink M, Mycko MP, et al., 2013, Neutrophil--CD4+CD25+ T Regulatory Cell Interactions: a Possible New Mechanism of Infectious Tolerance. Immunobiology, 218(4): 455-64.
[10] Chen HX, Xu HJ, Zhang W, et al., 2025, HucMSCs-derived Exosomes Protect Against 6-hydroxydopamineinduced Parkinson's Disease in Rats by Inhibiting Caspase-3 Expression and Suppressing Apoptosis. Curr Stem Cell Res Ther, 20(3): 266-278.