Generation of disease-specific autopsy-confirmed iPSCs lines from postmortem isolated Peripheral Blood Mononuclear Cells.
Understanding the molecular mechanisms that underlie neurodegenerative disorders has been hampered by a lack of readily available model systems that replicate the complexity of the human disease. Recent advances in stem cell technology have facilitated the derivation of patient-specific stem cells from a variety of differentiated cell types. These induced pluripotent stem cells (iPSCs) are attractive disease models since they can be grown and differentiated to produce large numbers of disease-relevant cell types. However, most iPSC lines are derived in advance of, and without the benefit of, neuropathological confirmation of the donor - the gold standard for many disease classifications and measurement of disease severity. While others have reported the generation of autopsy-confirmed iPSC lines from patient explants, these methods require outgrowth of cadaver tissue, which require additional time and is often only successful ∼50% of the time. Here we report the rapid generation of autopsy-confirmed iPSC lines from peripheral blood mononuclear cells (PBMCs) drawn postmortem. Since this approach doesn't require the propagation of previously frozen cadaver tissue, iPSC can be rapidly and efficiently produced from patients with autopsy-confirmed pathology. These matched iPSC-derived patient-specific neurons and postmortem brain tissue will support studies of specific mechanisms that drive the pathogenesis of neurodegenerative diseases.
Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami FL, United States.
Kinsley
K
Belle
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States.
Francelethia S
FS
Shabazz
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States.
Karen
K
Nuytemans
Department of Neurology, Miller School of Medicine, University of Miami, Miami FL, United States.
David A
DA
Davis
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States.
Aleena
A
Ali
Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami FL, United States; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States.
Juan L
JL
Young
Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami FL, United States; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States.
William K
WK
Scott
Department of Neurology, Miller School of Medicine, University of Miami, Miami FL, United States; Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami FL, United States.
Deborah C
DC
Mash
Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami FL, United States; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States.
Jeffrey M
JM
Vance
Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami FL, United States; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami FL, United States. Electronic address: DDykxhoorn@med.miami.edu.
Derek M
DM
Dykxhoorn
D001344:Autopsy / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000473:pathology
Autopsy; Disease modeling; Neurodegeneration; Neuropathological confirmation; PBMCs; Parkinson disease; Postmortem; iPSCs