IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

Daniela Lehnen; Serena Barral; Tiago Cardoso; Shane Grealish; Andreas Heuer; Andrej Smiyakin; Agnete Kirkeby; Jutta Kollet; Harold Cremer; Malin Parmar; Andreas Bosio; Sebastian. Knoebel

doi:10.1016/j.stemcr.2017.08.016

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

Daniela Lehnen, Serena Barral, Tiago Cardoso, Shane Grealish, Andreas Heuer, Andrej Smiyakin, Agnete Kirkeby, Jutta Kollet, Harold Cremer, Malin Parmar, Andreas Bosio, Sebastian. Knoebel

Laboratory

Research output: Contribution to journal › Journal article › peer-review

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Abstract

Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clin. translation of differentiation protocols requires standardization of prodn. procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-assocd. protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron d. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clin. cell replacement strategies. [on SciFinder(R)]

Original language	English
Journal	Stem Cell Reports
Volume	9
Issue number	4
Pages (from-to)	1207-1220
Number of pages	14
ISSN	2213-6711
DOIs	https://doi.org/10.1016/j.stemcr.2017.08.016
Publication status	Published - Oct 2017

Bibliographical note

M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.

CAPLUS AN 2017:1573803(Journal; Online Computer File)

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10.1016/j.stemcr.2017.08.016

1-s2.0-S2213671117303739-mainFinal published version, 4.92 MBLicence: CC BY-NC-ND

Cite this

Lehnen, D., Barral, S., Cardoso, T., Grealish, S., Heuer, A., Smiyakin, A., Kirkeby, A., Kollet, J., Cremer, H., Parmar, M., Bosio, A., & Knoebel, S. (2017). IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells. Stem Cell Reports, 9(4), 1207-1220. https://doi.org/10.1016/j.stemcr.2017.08.016

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells. / Lehnen, Daniela; Barral, Serena; Cardoso, Tiago; Grealish, Shane; Heuer, Andreas; Smiyakin, Andrej; Kirkeby, Agnete; Kollet, Jutta; Cremer, Harold; Parmar, Malin; Bosio, Andreas; Knoebel, Sebastian.

In: Stem Cell Reports, Vol. 9, No. 4, 10.2017, p. 1207-1220.

Research output: Contribution to journal › Journal article › peer-review

Lehnen, D, Barral, S, Cardoso, T, Grealish, S, Heuer, A, Smiyakin, A, Kirkeby, A, Kollet, J, Cremer, H, Parmar, M, Bosio, A & Knoebel, S 2017, 'IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.', Stem Cell Reports, vol. 9, no. 4, pp. 1207-1220. https://doi.org/10.1016/j.stemcr.2017.08.016

Lehnen, Daniela ; Barral, Serena ; Cardoso, Tiago ; Grealish, Shane ; Heuer, Andreas ; Smiyakin, Andrej ; Kirkeby, Agnete ; Kollet, Jutta ; Cremer, Harold ; Parmar, Malin ; Bosio, Andreas ; Knoebel, Sebastian. / IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells. In: Stem Cell Reports. 2017 ; Vol. 9, No. 4. pp. 1207-1220.

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title = "IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.",

abstract = "Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clin. translation of differentiation protocols requires standardization of prodn. procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-assocd. protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron d. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clin. cell replacement strategies. [on SciFinder(R)]",

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AU - Lehnen, Daniela

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AU - Grealish, Shane

AU - Heuer, Andreas

AU - Smiyakin, Andrej

AU - Kirkeby, Agnete

AU - Kollet, Jutta

AU - Cremer, Harold

AU - Parmar, Malin

AU - Bosio, Andreas

AU - Knoebel, Sebastian.

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N2 - Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clin. translation of differentiation protocols requires standardization of prodn. procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-assocd. protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron d. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clin. cell replacement strategies. [on SciFinder(R)]

AB - Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clin. translation of differentiation protocols requires standardization of prodn. procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-assocd. protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron d. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clin. cell replacement strategies. [on SciFinder(R)]

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