Comparison of transplant efficiency between spontaneously derived and noggin-primed human embryonic stem cell neural precursors in the quinolinic acid rat model of Huntington's disease.
Human neural precursors (hNP) derived from embryonic stem cells (hESC) may provide a viable cellular source for transplantation therapy for Huntington's disease (HD). However, developing effective transplantation therapy for the central nervous system (CNS) using hESC relies on optimizing the in vitro production of hNP to control appropriate in vivo posttransplantation neuronal differentiation. The current study provides the first direct in vivo comparison of the transplant efficiency and posttransplantation characteristics of spontaneously derived and noggin-primed hNP following transplantation into the quinolinic acid (QA) rat model of HD. We show that spontaneously derived and noggin-primed hNP both survived robustly up to 8 weeks after transplantation into the QA-lesioned striatum of the adult rat. Transplanted hNP underwent extensive migration and large-scale differentiation towards a predominantly neuronal fate by 8 weeks posttransplantation. Furthermore, in vitro noggin priming of hNP specifically increased the extent of neuronal differentiation at both 4 and 8 weeks posttransplantation when compared to spontaneously derived hNP grafts. The results of this study suggest that in vitro noggin priming provides an effective mechanism by which to enhance hNP transplant efficiency for the treatment of HD.
Vazey
Elena M
EM
Department of Pharmacology and Clinical Pharmacology, FMHS, University of Auckland, Auckland, New Zealand.
Dottori
Mirella
M
Jamshidi
Pegah
P
Tomas
Doris
D
Pera
Martin F
MF
Horne
Malcolm
M
Connor
Bronwen
B
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000637:transplantation*; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects / Q000637:transplantation*; D009474:Neurons / Q000637:transplantation*; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D000099176:Noggin Protein
D002352:Carrier Proteins; D017378:Quinolinic Acid; D000099176:Noggin Protein