Fahn, S. The 200-year journey of Parkinson disease: Reflecting on the past and looking towards the future. Parkinsonism Relat. Disord. 46, S1–S5 (2018).
Kalia, L. V. & Lang, A. E. Parkinson’s disease. Lancet 386, 896–912 (2015).
Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Primers 3, 17013 (2017).
Obeso, J. A. et al. Missing pieces in the Parkinson’s disease puzzle. Nat. Med. 16, 653–661 (2010).
Meissner, W. G. et al. Priorities in Parkinson’s disease research. Nat. Rev. Drug Discov. 10, 377–393 (2011).
Barker, R. A., Barrett, J., Mason, S. L. & Bjorklund, A. Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson’s disease. Lancet Neurol. 12, 84–91 (2013).
Sonntag, K. C. et al. Pluripotent stem cell-based therapy for Parkinson’s disease: Current status and future prospects. Prog. Neurobiol. 168, 1–20 (2018).
Parmar, M., Grealish, S. & Henchcliffe, C. The future of stem cell therapies for Parkinson disease. Nat. Rev. Neurosci. 21, 103–115 (2020).
Barker, R. A., Drouin-Ouellet, J. & Parmar, M. Cell-based therapies for Parkinson disease-past insights and future potential. Nat. Rev. Neurol. 11, 492–503 (2015).
Skidmore, S. & Barker, R. A. Challenges in the clinical advancement of cell therapies for Parkinson’s disease. Nat. Biomed. Eng. 7, 370–386 (2023).
Cha, Y., Park, T. Y., Leblanc, P. & Kim, K. S. Current status and future perspectives on stem cell-based therapies for Parkinson’s disease. J. Mov. Disord. 16, 22–41 (2023).
Lindvall, O. Clinical translation of stem cell transplantation in Parkinson’s disease. J. Intern. Med. 279, 30–40 (2016).
Li, J. Y. & Li, W. Postmortem studies of fetal grafts in Parkinson’s Disease: What lessons have we learned? Front. Cell. Dev. Biol. 9, 666675 (2021).
Lindvall, O. et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 247, 574–577 (1990).
Defer, G. L. et al. Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach. Brain 119, 41–50 (1996).
Mendez, I. et al. Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases. J. Neurosurg. 96, 589–596 (2002).
Peschanski, M. et al. Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson’s disease following intrastriatal transplantation of foetal ventral mesencephalon. Brain 117, 487–499 (1994).
Freed, C. R. et al. Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N. Engl. J. Med. 327, 1549–1555 (1992).
Freeman, T. B. et al. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson’s disease. Ann. Neurol. 38, 379–388 (1995).
Hagell, P. et al. Sequential bilateral transplantation in Parkinson’s disease: Effects of the second graft. Brain 122, 1121–1132 (1999).
Kefalopoulou, Z. et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: Two case reports. JAMA Neurol. 71, 83–87 (2014).
Kordower, J. H. et al. Functional fetal nigral grafts in a patient with Parkinson’s disease: chemoanatomic, ultrastructural, and metabolic studies. J. Comp. Neurol. 370, 203–230 (1996).
Kordower, J. H. et al. Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson’s disease. Mov. Disord. 13, 383–393 (1998).
Lindvall, O. et al. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. A detailed account of methodology and a 6-month follow-up. Arch. Neurol. 46, 615–631 (1989).
Lindvall, O. et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann. Neurol. 35, 172–180 (1994).
Lindvall, O. et al. Transplantation of fetal dopamine neurons in Parkinson’s disease: one-year clinical and neurophysiological observations in two patients with putaminal implants. Ann. Neurol. 31, 155–165 (1992).
Mendez, I. et al. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain 128, 1498–1510 (2005).
Piccini, P. et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient. Nat. Neurosci. 2, 1137–1140 (1999).
Spencer, D. D. et al. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N. Engl. J. Med. 327, 1541–1548 (1992).
Wenning, G. K. et al. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson’s disease. Ann. Neurol. 42, 95–107 (1997).
Widner, H. et al. Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N. Engl. J. Med. 327, 1556–1563 (1992).
Li, W. et al. Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain. Proc. Natl. Acad. Sci. USA 113, 6544–6549 (2016).
Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B. & Olanow, C. W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat. Med. 14, 504–506 (2008).
Li, J. Y. et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat. Med. 14, 501–503 (2008).
Mendez, I. et al. Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat. Med. 14, 507–509 (2008).
Greene, P. E. et al. Persistent dyskinesias in patients with fetal tissue transplantation for Parkinson disease. NPJ Parkinsons Dis. 7, 38 (2021).
Freed, C. R. et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N. Engl. J. Med. 344, 710–719 (2001).
Olanow, C. W. et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann. Neurol. 54, 403–414 (2003).
Thompson, L. & Bjorklund, A. Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation. Prog. Brain Res. 200, 61–95 (2012).
Ramachandran, A. C., Bartlett, L. E. & Mendez, I. M. A multiple target neural transplantation strategy for Parkinson’s disease. Rev. Neurosci. 13, 243–256 (2002).
Castilho, R. F., Hansson, O. & Brundin, P. Improving the survival of grafted embryonic dopamine neurons in rodent models of Parkinson’s disease. Prog. Brain Res. 127, 203–231 (2000).
Bjorklund, A. & Kordower, J. H. Cell therapy for Parkinson’s disease: what next? Mov. Disord. 28, 110–115 (2013).
Brundin, P. et al. Improving the survival of grafted dopaminergic neurons: a review over current approaches. Cell Transpl. 9, 179–195 (2000).
Brundin, P. et al. Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp. Brain Res. 70, 192–208 (1988).
Frodl, E. M., Duan, W. M., Sauer, H., Kupsch, A. & Brundin, P. Human embryonic dopamine neurons xenografted to the rat: effects of cryopreservation and varying regional source of donor cells on transplant survival, morphology and function. Brain Res. 647, 286–298 (1994).
Barker, R. A., Dunnett, S. B., Faissner, A. & Fawcett, J. W. The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum. Exp. Neurol. 141, 79–93 (1996).
Duan, W. M., Widner, H. & Brundin, P. Temporal pattern of host responses against intrastriatal grafts of syngeneic, allogeneic or xenogeneic embryonic neuronal tissue in rats. Exp. Brain Res. 104, 227–242 (1995).
Emgard, M., Karlsson, J., Hansson, O. & Brundin, P. Patterns of cell death and dopaminergic neuron survival in intrastriatal nigral grafts. Exp. Neurol. 160, 279–288 (1999).
Wenker, S. D. & Pitossi, F. J. Cell therapy for Parkinson’s disease is coming of age: current challenges and future prospects with a focus on immunomodulation. Gene Ther. 27, 6–14 (2020).
Zawada, W. M. et al. Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats. Brain Res. 786, 96–103 (1998).
Schierle, G. S. et al. Caspase inhibition reduces apoptosis and increases survival of nigral transplants. Nat. Med. 5, 97–100 (1999).
Mahalik, T. J., Hahn, W. E., Clayton, G. H. & Owens, G. P. Programmed cell death in developing grafts of fetal substantia nigra. Exp. Neurol. 129, 27–36 (1994).
Zeng, B. Y., Jenner, P. & Marsden, C. D. Altered motor function and graft survival produced by basic fibroblast growth factor in rats with 6-OHDA lesions and fetal ventral mesencephalic grafts are associated with glial proliferation. Exp. Neurol. 139, 214–226 (1996).
Mayer, E., Fawcett, J. W. & Dunnett, S. B. Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons–II. Effects on nigral transplants in vivo. Neuroscience 56, 389–398 (1993).
Takayama, H. et al. Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson’s disease. Nat. Med. 1, 53–58 (1995).
Schierle, G. S. & Brundin, P. Excitotoxicity plays a role in the death of tyrosine hydroxylase- immunopositive nigral neurons cultured in serum-free medium. Exp. Neurol. 157, 338–348 (1999).
Nakao, N., Frodl, E. M., Duan, W. M., Widner, H. & Brundin, P. Lazaroids improve the survival of grafted rat embryonic dopamine neurons. Proc. Natl. Acad. Sci. USA 91, 12408–12412 (1994).
Kaminski Schierle, G. S., Hansson, O. & Brundin, P. Flunarizine improves the survival of grafted dopaminergic neurons. Neuroscience 94, 17–20 (1999).
Schweitzer, J. S., Song, B. & Kim, K. S. A step closer to autologous cell therapy for Parkinson’s disease. Cell Stem Cell 28, 595–597 (2021).
Merkle, F. T. et al. Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature 545, 229–233 (2017).
Schweitzer, J. S. et al. Personalized iPSC-Derived dopamine progenitor cells for parkinson’s disease. N. Engl. J. Med. 382, 1926–1932 (2020).
Lee, A. S., Tang, C., Rao, M. S., Weissman, I. L. & Wu, J. C. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat. Med. 19, 998–1004 (2013).
Yamanaka, S. Pluripotent stem cell-based cell therapy-promise and challenges. Cell Stem Cell 27, 523–531 (2020).
Lee, M. O. et al. Inhibition of pluripotent stem cell-derived teratoma formation by small molecules. Proc. Natl. Acad. Sci. USA 110, E3281–E3290 (2013).
Song, B. et al. Human autologous iPSC-derived dopaminergic progenitors restore motor function in Parkinson’s disease models. J. Clin. Invest. 130, 904–920 (2020).
Ostrom, Q. T. et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro. Oncol. 16, 896–913 (2014).
Lund, R. J., Narva, E. & Lahesmaa, R. Genetic and epigenetic stability of human pluripotent stem cells. Nat. Rev. Genet. 13, 732–744 (2012).
Yoshihara, M., Hayashizaki, Y. & Murakawa, Y. Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications. Stem Cell Rev. 13, 7–16 (2017).
Abyzov, A. et al. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492, 438–442 (2012).
Cheng, L. et al. Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. Cell Stem Cell 10, 337–344 (2012).
Gore, A. et al. Somatic coding mutations in human induced pluripotent stem cells. Nature 471, 63–67 (2011).
Howden, S. E. et al. Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy. Proc. Natl. Acad. Sci. USA 108, 6537–6542 (2011).
Quinlan, A. R. et al. Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Cell Stem Cell 9, 366–373 (2011).
Ji, J. et al. Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells 30, 435–440 (2012).
Sugiura, M. et al. Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells. Stem Cell Reports 2, 52–63 (2014).
Yoshihara, M. et al. Hotspots of de novo point mutations in induced pluripotent stem cells. Cell Rep. 21, 308–315 (2017).
Liu, P. et al. Passage number is a major contributor to genomic structural variations in mouse iPSCs. Stem Cells 32, 2657–2667 (2014).
Lezmi, E., Jung, J. & Benvenisty, N. High prevalence of acquired cancer-related mutations in 146 human pluripotent stem cell lines and their differentiated derivatives. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-02090-2 (2024).
Trounson, A. Potential pitfall of pluripotent stem cells. N. Engl. J. Med. 377, 490–491 (2017).
Wang, L. et al. Immunogenicity and functional evaluation of iPSC-derived organs for transplantation. Cell Discov. 1, 15015 (2015).
Guha, P., Morgan, J. W., Mostoslavsky, G., Rodrigues, N. P. & Boyd, A. S. Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell 12, 407–412 (2013).
Araki, R. et al. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 494, 100–104 (2013).
Zhao, T. et al. Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells. Cell Stem Cell 17, 353–359 (2015).
Park, T. Y. et al. Co-transplantation of autologous T(reg) cells in a cell therapy for Parkinson’s disease. Nature 619, 606–615 (2023).
Ozaki, M. et al. Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro. Stem Cell Res. 19, 128–138 (2017).
Kimura, T., Yamashita, A., Ozono, K. & Tsumaki, N. Limited immunogenicity of human induced pluripotent stem cell-derived cartilages. Tissue Eng. Part A 22, 1367–1375 (2016).
Alam, A. et al. Cellular infiltration in traumatic brain injury. J. Neuroinflammation 17, 328 (2020).
Karve, I. P., Taylor, J. M. & Crack, P. J. The contribution of astrocytes and microglia to traumatic brain injury. Br. J. Pharmacol. 173, 692–702 (2016).
Kirkeby, A. et al. Predictive markers guide differentiation to improve graft outcome in clinical translation of hESC-based therapy for Parkinson’s disease. Cell Stem Cell 20, 135–148 (2017).
Doi, D. et al. Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease. Nat. Commun. 11, 3369 (2020).
Gantner, C. W., Cota-Coronado, A., Thompson, L. H. & Parish, C. L. An optimized protocol for the generation of midbrain dopamine neurons under defined conditions. STAR Protoc. 1, 100065 (2020).
Xiong, M. et al. Human stem cell-derived neurons repair circuits and restore neural function. Cell Stem Cell 28, 112–126.e6 (2021).
Piao, J. et al. Preclinical efficacy and safety of a human embryonic stem cell-derived midbrain dopamine progenitor product, MSK-DA01. Cell Stem Cell 28, 217–229.e7 (2021).
Kriks, S. et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480, 547–551 (2011).
Kirkeby, A. et al. Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson’s disease, STEM-PD. Cell Stem Cell 30, 1299–1314.e9 (2023).
Park, S. et al. Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson’s disease. Cell Stem Cell 31, 25–38.e8 (2024).
Kim, J. et al. Spotting-based differentiation of functional dopaminergic progenitors from human pluripotent stem cells. Nat. Protoc. 17, 890–909 (2022).
Nikkhah, G., Eberhard, J., Olsson, M. & Bjorklund, A. Preservation of fetal ventral mesencephalic cells by cool storage: in-vitro viability and TH-positive neuron survival after microtransplantation to the striatum. Brain Res. 687, 22–34 (1995).
Barker, R. A., Fricker, R. A., Abrous, D. N., Fawcett, J. & Dunnett, S. B. A comparative study of preparation techniques for improving the viability of nigral grafts using vital stains, in vitro cultures, and in vivo grafts. Cell Transplant. 4, 173–200 (1995).
Watts, C., Caldwell, M. A. & Dunnett, S. B. The development of intracerebral cell-suspension implants is influenced by the grafting medium. Cell Transplant. 7, 573–583 (1998).
Wakeman, D. R. et al. Cryopreservation maintains functionality of human iPSC dopamine neurons and rescues Parkinsonian phenotypes in vivo. Stem Cell Reports 9, 149–161 (2017).
Hiramatsu, S. et al. Cryopreservation of induced pluripotent stem cell-derived dopaminergic neurospheres for clinical application. J. Parkinsons Dis. 12, 871–884 (2022).
Niclis, J. C. et al. Efficiently specified ventral midbrain dopamine neurons from human pluripotent stem cells under xeno-free conditions restore motor deficits in Parkinsonian rodents. Stem Cells Transl. Med. 6, 937–948 (2017).
Forrester, J. V., McMenamin, P. G. & Dando, S. J. CNS infection and immune privilege. Nat. Rev. Neurosci. 19, 655–671 (2018).
Zhao, T., Zhang, Z. N., Rong, Z. & Xu, Y. Immunogenicity of induced pluripotent stem cells. Nature 474, 212–215 (2011).
Lee, H. & Pienaar, I. S. Disruption of the blood-brain barrier in Parkinson’s disease: curse or route to a cure? Front. Biosci. 19, 272–280 (2014).
Waisman, A., Liblau, R. S. & Becher, B. Innate and adaptive immune responses in the CNS. Lancet Neurol. 14, 945–955 (2015).
Park, S. C. et al. Does age at onset of first major depressive episode indicate the subtype of major depressive disorder?: the clinical research center for depression study. Yonsei Med. J. 55, 1712–1720 (2014).
Cutolo, M. et al. Use of glucocorticoids and risk of infections. Autoimmun. Rev. 8, 153–155 (2008).
Stuck, A. E., Minder, C. E. & Frey, F. J. Risk of infectious complications in patients taking glucocorticosteroids. Rev. Infect. Dis. 11, 954–963 (1989).
Aberra, F. N. & Lichtenstein, G. R. Methods to avoid infections in patients with inflammatory bowel disease. Inflamm. Bowel Dis. 11, 685–695 (2005).
Price, M. L., Tidman, M. J., Ogg, C. S. & MacDonald, D. M. Skin cancer and cyclosporine therapy. N. Engl. J. Med. 313, 1420 (1985).
Muellenhoff, M. W. & Koo, J. Y. Cyclosporine and skin cancer: an international dermatologic perspective over 25 years of experience. A comprehensive review and pursuit to define safe use of cyclosporine in dermatology. J. Dermatolog. Treat. 23, 290–304 (2012).
Alemdar, A. Y., Sadi, D., McAlister, V. & Mendez, I. Intracerebral co-transplantation of liposomal tacrolimus improves xenograft survival and reduces graft rejection in the hemiparkinsonian rat. Neuroscience 146, 213–224 (2007).
Huber-Lang, M., Lambris, J. D. & Ward, P. A. Innate immune responses to trauma. Nat. Immunol. 19, 327–341 (2018).
Duan, T., Du, Y., Xing, C., Wang, H. Y. & Wang, R. F. Toll-Like receptor signaling and its role in cell-mediated immunity. Front. Immunol. 13, 812774 (2022).
Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783–801 (2006).
Zheng, R. Z. et al. Neuroinflammation following traumatic brain injury: Take it seriously or not. Front. Immunol. 13, 855701 (2022).
Collins, L. M., Toulouse, A., Connor, T. J. & Nolan, Y. M. Contributions of central and systemic inflammation to the pathophysiology of Parkinson’s disease. Neuropharmacology 62, 2154–2168 (2012).
Yacoubian, T. A. et al. Brain and systemic inflammation in de novo Parkinson’s disease. Mov. Disord. 38, 743–754 (2023).
Tansey, M. G. et al. Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol. 22, 657–673 (2022).
Miyawaki, Y., Samata, B., Kikuchi, T., Nishimura, K. & Takahashi, J. Zonisamide promotes survival of human-induced pluripotent stem cell-derived dopaminergic neurons in the striatum of female rats. J. Neurosci. Res. 98, 1575–1587 (2020).
Gantner, C. W. et al. Viral Delivery of GDNF promotes functional integration of human stem cell grafts in Parkinson’s disease. Cell Stem Cell 26, 511–526.e5 (2020).
Kikuchi, T. et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 548, 592–596 (2017).
Samata, B. et al. Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1. Nat. Commun. 7, 13097 (2016).
Chen, Y. et al. Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson’s Disease. Cell Stem Cell 18, 817–826 (2016).
Doi, D. et al. Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation. Stem Cell Reports 2, 337–350 (2014).
Grealish, S. et al. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease. Cell Stem Cell 15, 653–665 (2014).
Sundberg, M. et al. Improved cell therapy protocols for Parkinson’s disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31, 1548–1562 (2013).
Doi, D. et al. Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson’s disease. Stem Cells 30, 935–945 (2012).
Kikuchi, T. et al. Survival of human induced pluripotent stem cell-derived midbrain dopaminergic neurons in the brain of a primate model of Parkinson’s disease. J. Parkinsons Dis. 1, 395–412 (2011).
Emborg, M. E. et al. Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell Rep. 3, 646–650 (2013).
Tao, Y. et al. Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys. Nat. Med. 27, 632–639 (2021).
Hallett, P. J. et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson’s disease. Cell Stem Cell 16, 269–274 (2015).
de Rham, C. & Villard, J. Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy. J. Immunol. Res. 2014, 518135 (2014).
Ford, E. et al. Human Pluripotent stem cells-based therapies for neurodegenerative diseases: current status and challenges. Cells 9, 2517 (2020).
Akabayashi, A., Nakazawa, E. & Jecker, N. S. Endangerment of the iPSC stock project in Japan: on the ethics of public funding policies. J. Med. Ethics 44, 700–702 (2018).
Gourraud, P. A., Gilson, L., Girard, M. & Peschanski, M. The role of human leukocyte antigen matching in the development of multiethnic “haplobank” of induced pluripotent stem cell lines. Stem Cells 30, 180–186 (2012).
Morizane, A. et al. MHC matching improves engraftment of iPSC-derived neurons in non-human primates. Nat. Commun. 8, 385 (2017).
Mizukami, Y. et al. MHC-matched induced pluripotent stem cells can attenuate cellular and humoral immune responses but are still susceptible to innate immunity in pigs. PLoS One 9, e98319 (2014).
Lanza, R., Russell, D. W. & Nagy, A. Engineering universal cells that evade immune detection. Nat. Rev. Immunol. 19, 723–733 (2019).
Simpson, A., Hewitt, A. W. & Fairfax, K. A. Universal cell donor lines: A review of the current research. Stem Cell Reports 18, 2038–2046 (2023).
Riolobos, L. et al. HLA engineering of human pluripotent stem cells. Mol. Ther. 21, 1232–1241 (2013).
Lu, P. et al. Generating hypoimmunogenic human embryonic stem cells by the disruption of beta 2-microglobulin. Stem Cell Rev. Rep. 9, 806–813 (2013).
Bix, M. et al. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349, 329–331 (1991).
Gornalusse, G. G. et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat. Biotechnol. 35, 765–772 (2017).
Deuse, T. et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat. Biotechnol. 37, 252–258 (2019).
Xu, H. et al. Targeted disruption of HLA genes via CRISPR-Cas9 generates iPSCs with enhanced immune compatibility. Cell Stem Cell 24, 566–578.e7 (2019).
Shani, T. & Hanna, J. H. Universally non-immunogenic iPSCs. Nat. Biomed. Eng. 3, 337–338 (2019).
Trounson, A., Boyd, N. R. & Boyd, R. L. Toward a universal solution: Editing compatibility into pluripotent stem cells. Cell Stem Cell 24, 508–510 (2019).
Kosicki, M., Tomberg, K. & Bradley, A. Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat. Biotechnol. 36, 765–771 (2018).
Liang, Q. et al. Linking a cell-division gene and a suicide gene to define and improve cell therapy safety. Nature 563, 701–704 (2018).
Harding, J., Vintersten-Nagy, K. & Nagy, A. Universal stem cells: Making the unsafe safe. Cell Stem Cell 27, 198–199 (2020).
Morganti-Kossmann, M. C., Rancan, M., Otto, V. I., Stahel, P. F. & Kossmann, T. Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock 16, 165–177 (2001).
Helmy, A., Carpenter, K. L., Menon, D. K., Pickard, J. D. & Hutchinson, P. J. The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production. J. Cereb. Blood Flow Metab. 31, 658–670 (2011).
Yang, S. H., Gangidine, M., Pritts, T. A., Goodman, M. D. & Lentsch, A. B. Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice. Shock 40, 471–475 (2013).
Clausen, F. et al. Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice. Eur. J. Neurosci. 30, 385–396 (2009).
Kabadi, S. V. et al. S100B inhibition reduces behavioral and pathologic changes in experimental traumatic brain injury. J. Cereb. Blood Flow Metab. 35, 2010–2020 (2015).
Chio, C. C. et al. Therapeutic evaluation of etanercept in a model of traumatic brain injury. J. Neurochem. 115, 921–929 (2010).
Zietlow, R., Sinclair, S. R., Schwiening, C. J., Dunnett, S. B. & Fawcettt, J. W. The release of excitatory amino acids, dopamine, and potassium following transplantation of embryonic mesencephalic dopaminergic grafts to the rat striatum, and their effects on dopaminergic neuronal survival in vitro. Cell Transplant. 11, 637–652 (2002).
Sinclair, S. R., Fawcett, J. W. & Dunnett, S. B. Delayed implantation of nigral grafts improves survival of dopamine neurones and rate of functional recovery. Neuroreport 10, 1263–1267 (1999).
Vignali, D. A., Collison, L. W. & Workman, C. J. How regulatory T cells work. Nat. Rev. Immunol. 8, 523–532 (2008).
Wood, K. J. & Sakaguchi, S. Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 3, 199–210 (2003).
Bluestone, J. A., McKenzie, B. S., Beilke, J. & Ramsdell, F. Opportunities for Treg cell therapy for the treatment of human disease. Front. Immunol. 14, 1166135 (2023).
Shi, L. et al. Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. Immunity 54, 1527–1542.e8 (2021).
Ma, X. et al. Regulatory T cells protect against brain damage by alleviating inflammatory response in neuromyelitis optica spectrum disorder. J. Neuroinflammation 18, 201 (2021).
Duggleby, R., Danby, R. D., Madrigal, J. A. & Saudemont, A. Clinical grade regulatory CD4(+) T Cells (Tregs): Moving toward cellular-based immunomodulatory therapies. Front. Immunol. 9, 252 (2018).
Penna, V. et al. Extracellular matrix biomimetic hydrogels, encapsulated with stromal cell-derived factor 1, improve the composition of foetal tissue grafts in a rodent model of Parkinson’s disease. Int. J. Mol. Sci. 23, 4646 (2022).
Moriarty, N., Cabre, S., Alamilla, V., Pandit, A. & Dowd, E. Encapsulation of young donor age dopaminergic grafts in a GDNF-loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi-Parkinsonian rats. Eur. J. Neurosci. 49, 487–496 (2019).
Adil, M. M. et al. Engineered hydrogels increase the post-transplantation survival of encapsulated hESC-derived midbrain dopaminergic neurons. Biomaterials 136, 1–11 (2017).
Tang, Q. Regulatory T cells aid stem-cell therapy for Parkinson’s disease. Nature 619, 470–472 (2023).
Hoban, D. B. et al. Impact of alpha-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized alpha-synuclein rat model of PD. Proc. Natl. Acad. Sci. USA 117, 15209–15220 (2020).
Nolan, Y. M., Sullivan, A. M. & Toulouse, A. Parkinson’s disease in the nuclear age of neuroinflammation. Trends Mol. Med. 19, 187–196 (2013).
Tiklova, K. et al. Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease. Nat. Commun. 11, 2434 (2020).
Di Santo, S., Meyer, M., Ducray, A. D., Andereggen, L. & Widmer, H. R. A Combination of NT-4/5 and GDNF is favorable for cultured human nigral neural progenitor cells. Cell Transplant. 27, 648–653 (2018).
Studer, L. & Tabar, V. Parkinson’s disease grafts benefit from well-timed growth factor. Nature 582, 39–40 (2020).
Moriarty, N. et al. A combined cell and gene therapy approach for homotopic reconstruction of midbrain dopamine pathways using human pluripotent stem cells. Cell Stem Cell 29, 434–448.e5 (2022).
Nahimi, A., Kinnerup, M. B., Sommerauer, M., Gjedde, A. & Borghammer, P. Molecular imaging of the noradrenergic system in idiopathic Parkinson’s disease. Int. Rev. Neurobiol. 141, 251–274 (2018).
Espay, A. J., LeWitt, P. A. & Kaufmann, H. Norepinephrine deficiency in Parkinson’s disease: the case for noradrenergic enhancement. Mov. Disord. 29, 1710–1719 (2014).
Samanci, B., Tan, S., Michielse, S., Kuijf, M. L. & Temel, Y. The habenula in Parkinson’s disease: Anatomy, function, and implications for mood disorders – A narrative review. J. Chem. Neuroanat. 136, 102392 (2024).
Vegas-Suarez, S. et al. Dysfunction of serotonergic neurons in Parkinson’s disease and dyskinesia. Int. Rev. Neurobiol. 146, 259–279 (2019).
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- Source: https://www.nature.com/articles/s41422-024-00971-y