Limited proliferation capacity of mesencepahlic neural progenitor cells derived from human embryonic stem cells
(English)Manuscript (Other academic)
Midbrain neural progenitor cells (NPC) derived from human embryonic stem cells(hESC) may be useful for development of novel transplantation and gene deliverystrategies. One of the major goals of human transplantation research has been to developa means of generating dopaminergic (DA) neurons in vitro, which can be employed fortransplantation. NPC can be generated from hESC using a number of strategies. Thephenotypic conservation, stability, and differentiation of NPC generated under variousconditions are, however, not well understood. In the present study we generatedexpandable mesencephalic-restricted human NPC from the hESC line BG01V2 under theinfluence of stromal-derived inducing activity (SDIA), and assessed their capacity forproliferation and maintenance of cellular memory. The NPC could be expanded by fivefoldas neurospheres for up to 2 weeks in vitro while retaining their DA differentiationpotential, without a substantial loss of cellular memory and viability. Although cellswere continuously maintained under the influence of the midbrain patterning factors SHHand FGF8, they progressively lost their ability to differentiate to DA neurons andmaintain a stable phenotype in vitro. Preliminary transplantation experiments ofneurospheres with midbrain identity in intrastriatal 6-hydroxydopamine lesioned animalsindicated, however, that these cells could survive and conserve their phenotype in vivo.Therefore, in vitro propagation of SDIA-derived NPC under the present conditions resultsin a gradual loss of growth capacity and multipotency over time, whereas the phenotypeof transplanted NPC remains unaltered.
Stromal-derived inducing activity, Neural progenitor cells, Neurpsphere
IdentifiersURN: urn:nbn:se:kth:diva-9613OAI: oai:DiVA.org:kth-9613DiVA: diva2:126725
QC 201009162008-11-202008-11-202010-09-16Bibliographically approved