摘要
For decades,clinicians have developed medications and therapies to alleviate the symptoms of Parkinson’s disease,but no treatment currently can slow or even stop the progression of this localized neurodegeneration.Fortunately,sparked by the genetic revolution,stem cell reprogramming research and the advancing capabilities of personalization in medicine enable forward-thinking to unprecedented patient-specific modeling and cell therapies for Parkinson’s disease using induced pluripotent stem cells(iPSCs).In addition to modeling Parkinson’s disease more accurately than chemically-induced animal models,patient-specific stem cell lines can be created,elucidating the effects of genetic susceptibility and sub-populations’differing responses to in vitro treatments.Sourcing cell therapy with iPSC lines provides ethical advantages because these stem cell lines do not require the sacrifice of human zygotes and genetically-specific drug trails can be tested in vitro without lasting damage to patients.In hopes of finally slowing the progression of Parkinson’s disease or re-establishing function,iPSC lines can ultimately be corrected with gene therapy and used as cell sources for neural transplantation for Parkinson’s disease.With relatively localized neural degeneration,similar to spinal column injury,Parkinson’s disease presents a better candidacy for cell therapy when compared to other diffuse degeneration found in Alzheimer’s or Huntington’s Disease.Neurosurgical implantation of pluripotent cells poses the risk of an innate immune response and tumorigenesis.Precautions,therefore,must be taken to ensure cell line quality before transplantation.While cell quality can be quantified using a number of assays,a yielding a high percentage of therapeutically relevant dopaminergic neurons,minimal de novo genetic mutations,and standard chromosomal structure is of the utmost importance.Current techniques focus on iPSCs because they can be matched with donors using human leukocyte antigens,thereby reducing the severity and risk of immune rejection.In August of 2018,researchers in Kyoto,Japan embarked on the first human clinical trial using iPSC cell therapy transplantation for patients with moderate Parkinson’s disease.Transplantation of many cell sources has already proven to reduce Parkinson’s disease symptoms in mouse and primate models.Here we discuss the history and implications for cell therapy for Parkinson’s disease,as well as the necessary safety standards needed for using iPSC transplantation to slow or halt the progression of Parkinson’s disease.
For decades, clinicians have developed medications and therapies to alleviate the symptoms of Parkinson’s disease, but no treatment currently can slow or even stop the progression of this localized neurodegeneration. Fortunately, sparked by the genetic revolution, stem cell reprogramming research and the advancing capabilities of personalization in medicine enable forward-thinking to unprecedented patient-specific modeling and cell therapies for Parkinson’s disease using induced pluripotent stem cells(iPSCs). In addition to modeling Parkinson’s disease more accurately than chemically-induced animal models, patient-specific stem cell lines can be created, elucidating the effects of genetic susceptibility and sub-populations’ differing responses to in vitro treatments. Sourcing cell therapy with iPSC lines provides ethical advantages because these stem cell lines do not require the sacrifice of human zygotes and genetically-specific drug trails can be tested in vitro without lasting damage to patients. In hopes of finally slowing the progression of Parkinson’s disease or re-establishing function, iPSC lines can ultimately be corrected with gene therapy and used as cell sources for neural transplantation for Parkinson’s disease. With relatively localized neural degeneration, similar to spinal column injury, Parkinson’s disease presents a better candidacy for cell therapy when compared to other diffuse degeneration found in Alzheimer’s or Huntington’s Disease. Neurosurgical implantation of pluripotent cells poses the risk of an innate immune response and tumorigenesis. Precautions, therefore, must be taken to ensure cell line quality before transplantation. While cell quality can be quantified using a number of assays, a yielding a high percentage of therapeutically relevant dopaminergic neurons, minimal de novo genetic mutations, and standard chromosomal structure is of the utmost importance. Current techniques focus on iPSCs because they can be matched with donors using human leukocyte antigens, thereby reducing the severity and risk of immune rejection. In August of 2018, researchers in Kyoto, Japan embarked on the first human clinical trial using iPSC cell therapy transplantation for patients with moderate Parkinson’s disease. Transplantation of many cell sources has already proven to reduce Parkinson’s disease symptoms in mouse and primate models. Here we discuss the history and implications for cell therapy for Parkinson’s disease, as well as the necessary safety standards needed for using iPSC transplantation to slow or halt the progression of Parkinson’s disease.
基金
supported by the Mallett Family
