Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson’s disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, ce...
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Published in | Nature communications Vol. 7; no. 1; p. 13097 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
14.10.2016
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson’s disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed, but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells expressing both CORIN and LMX1A::GFP, and report a cell surface marker to enrich mDA progenitors, LRTM1. When transplanted into 6-OHDA-lesioned rats, human iPSC-derived LRTM1
+
cells survive and differentiate into mDA neurons
in vivo
, resulting in a significant improvement in motor behaviour without tumour formation. In addition, there was marked survival of mDA neurons following transplantation of LRTM1
+
cells into the brain of an MPTP-treated monkey. Thus, LRTM1 may provide a tool for efficient and safe cell therapy for PD patients.
Midbrain dopaminergic neurons generated from stem cells show promise for the treatment of Parkinson’s disease. Here, the authors use the cell surface marker, LRTM1, to enrich the midbrain dopaminergic progenitors and show improved motor function/cell survival when grafted into rat/monkey brains, respectively. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms13097 |