title: Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?
abstract: Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials. The scarcity of human fetal tissue, and the logistics of coordinating collection and dissection of tissue with neurosurgical procedures makes the use of fetal tissue for this purpose both complex and limiting. Alternative donor cell sources which are expandable in culture prior to transplantation are currently being sought. Two potential donor cell sources which have received most attention recently are embryonic stem (ES) cells and adult induced pluripotent stem (iPS) cells, both of which can be directed to MSN-like fates, although achieving a genuine MSN fate has proven to be difficult. All potential donor sources have challenges in terms of their clinical application for regenerative medicine, and thus it is important to continue exploring a wide variety of expandable cells. In this review we discuss two less well-reported potential donor cell sources; embryonic germ (EG) cells and fetal neural precursors (FNPs), both are which are fetal-derived and have some properties that could make them useful for regenerative medicine applications.
authors.affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK.
authors.forename: Sophie V
authors.initials: SV
authors.lastname: Precious
authors.affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK.
authors.forename: Rike
authors.initials: R
authors.lastname: Zietlow
authors.affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; Wales Brain Repair and Intracranial Neurotherapeutics Unit (B.R.A.I.N), School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
authors.affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; School of Health Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff, CF5 2YB, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Kelly
authors.affiliation: Brain Repair Group, Sir Martin Evans Building, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; Wales Brain Repair and Intracranial Neurotherapeutics Unit (B.R.A.I.N), School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK. Electronic address: rosserae@cf.ac.uk.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Rosser
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000502:physiology / Q000637:transplantation*; D006801:Humans; D006816:Huntington Disease / Q000473:pathology / Q000628:therapy*; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000639:trends*
keywords: Cell therapy; Fetal-derived neural precursors; Human embryonic germ cells; Huntington's disease; Neural transplantation; Stem cell