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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

Journal Article


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Abstract


  • 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 post-transplantation. 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 vit ro noggin priming provides an effective mechanism by which to enhance hNP transplant efficiency for the treatment of HD.

Authors


  •   Vazey, Elena (external author)
  •   Dottori, Mirella
  •   Jamshidi, Pegah (external author)
  •   Tomas, Doris (external author)
  •   Pera, Martin F. (external author)
  •   Horne, Malcolm (external author)
  •   Connor, Bronwen (external author)

Publication Date


  • 2010

Citation


  • Vazey, E. M., Dottori, M., Jamshidi, P., Tomas, D., Pera, M. F., Horne, M. & Connor, B. (2010). 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. Cell Transplantation, 19 (8), 1055-1062.

Scopus Eid


  • 2-s2.0-78349259276

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2203&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1176

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1055

End Page


  • 1062

Volume


  • 19

Issue


  • 8

Place Of Publication


  • United States

Abstract


  • 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 post-transplantation. 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 vit ro noggin priming provides an effective mechanism by which to enhance hNP transplant efficiency for the treatment of HD.

Authors


  •   Vazey, Elena (external author)
  •   Dottori, Mirella
  •   Jamshidi, Pegah (external author)
  •   Tomas, Doris (external author)
  •   Pera, Martin F. (external author)
  •   Horne, Malcolm (external author)
  •   Connor, Bronwen (external author)

Publication Date


  • 2010

Citation


  • Vazey, E. M., Dottori, M., Jamshidi, P., Tomas, D., Pera, M. F., Horne, M. & Connor, B. (2010). 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. Cell Transplantation, 19 (8), 1055-1062.

Scopus Eid


  • 2-s2.0-78349259276

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2203&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1176

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1055

End Page


  • 1062

Volume


  • 19

Issue


  • 8

Place Of Publication


  • United States