| Related Articles |
THE SUBSTANTIA NIGRA IS PERMISSIVE AND GAINS INDUCTIVE SIGNALS WHEN LESIONED FOR DOPAMINERGIC DIFFERENTIATION OF EMBRYONIC STEM CELLS.
Stem Cells Dev. 2019 May 29;:
Authors: Collazo-Navarrete O, Hernández-García D, Guerrero-Flores G, Drucker-Colín R, Guerra-Crespo M, Covarrubias L
Abstract
Transplantation of dopaminergic (DA) cells into the striatum can rescue from dopamine deficiency in a Parkinson's disease condition, but this is not a suitable procedure for regaining the full control of motor activity. The minimal condition towards recovering the nigrostriatal pathway is the proper innervation of transplanted DA neurons or their precursors from the SNpc to their target areas. However, functional integration of transplanted cells would require first that the host SNpc is suitable for their survival and/or differentiation. We recently reported that the intact adult SNpc holds a strong neurogenic environment, but primed embryonic stem cells (i.e., embryoid body cells, EBCs) could not derive into DA neurons. In the present work, we transplanted into the intact or lesioned SNpc, EBCs derived from embryonic stem cells that were prompt to differentiate into DA neurons by the forced expression of Lmx1a in neural precursor cells (R1B5/NesE-Lmx1a). We observed that, 6-days post-transplantation (dpt), R1B5 or R1B5/NesE-Lmx1a EBCs gave rise to Nes+ and Dcx+ cells within the host SNpc, but a large number of Th+ cells derived only from EBCs exogenously expressing Lmx1a. In contrast, when transplantation was done into the 6-hydroxidopamine-lesioned SNpc, the emergence of Th+ cells from EBCs was independent of exogenous Lmx1a expression, though these cells were not found by 15 dpt. These results suggest that the adult SNpc is not only a permissive niche for initiation of DA differentiation of non-neuralized cells but also releases factors upon damage that promote the acquisition of DA characteristics by transplanted EBCs.
Transplantation of dopaminergic (DA) cells into the striatum can rescue from dopamine deficiency in a Parkinson's disease condition, but this is not a suitable procedure for regaining the full control of motor activity. The minimal condition towards recovering the nigrostriatal pathway is the proper innervation of transplanted DA neurons or their precursors from the SNpc to their target areas. However, functional integration of transplanted cells would require first that the host SNpc is suitable for their survival and/or differentiation. We recently reported that the intact adult SNpc holds a strong neurogenic environment, but primed embryonic stem cells (i.e., embryoid body cells, EBCs) could not derive into DA neurons. In the present work, we transplanted into the intact or lesioned SNpc, EBCs derived from embryonic stem cells that were prompt to differentiate into DA neurons by the forced expression of Lmx1a in neural precursor cells (R1B5/NesE-Lmx1a). We observed that, 6-days post-transplantation (dpt), R1B5 or R1B5/NesE-Lmx1a EBCs gave rise to Nes+ and Dcx+ cells within the host SNpc, but a large number of Th+ cells derived only from EBCs exogenously expressing Lmx1a. In contrast, when transplantation was done into the 6-hydroxidopamine-lesioned SNpc, the emergence of Th+ cells from EBCs was independent of exogenous Lmx1a expression, though these cells were not found by 15 dpt. These results suggest that the adult SNpc is not only a permissive niche for initiation of DA differentiation of non-neuralized cells but also releases factors upon damage that promote the acquisition of DA characteristics by transplanted EBCs.
PMID: 31140356 [PubMed - as supplied by publisher]
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου