Single-cell high content imaging parameters predict functional phenotype of cultured human bone marrow stromal stem cells

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Resumé

Cultured human bone marrow stromal (mesenchymal) stem cells (hBM-MSCs) are heterogenous cell populations exhibiting variable biological properties. Quantitative high-content imaging technology allows identification of morphological markers at a single cell resolution that are determinant for cellular functions. We determined the morphological characteristics of cultured primary hBM-MSCs and examined their predictive value for hBM-MSC functionality. BM-MSCs were isolated from 56 donors and characterized for their proliferative and differentiation potential. We correlated these data with cellular and nuclear morphological features determined by Operetta; a high-content imaging system. Cell area, cell- and nucleus geometry of cultured hBM-MSCs exhibited significant correlation with expression of hBM-MSC membrane markers: ALP, CD146, CD271. Proliferation capacity correlated negatively with cell and nucleus area and positively with cytoskeleton texture features. In addition, in vitro differentiation to osteoblasts as well as in vivo heterotopic bone formation was associated with decreased ratio of nucleus width to length. Multivariable analysis applying a stability selection procedure identified nuclear geometry and texture as predictors for hBM-MSCs differentiation potential to osteoblasts or adipocytes. Our data demonstrate that by employing a limited number of cell morphological characteristics, it is possible to predict the functional phenotype of cultured hBM-MSCs and thus can be used as a screening test for "quality" of hBM-MSCs prior their use in clinical protocols. Stem Cells Translational Medicine 2019.

OriginalsprogEngelsk
TidsskriftStem Cells Translational Medicine
ISSN2157-6564
DOI
StatusE-pub ahead of print - 23. nov. 2019

Fingeraftryk

Mesenchymal Stromal Cells
Osteoblasts
Translational Medical Research
Adipocytes
Osteogenesis
Cell Differentiation
Cell Membrane
Population

Bibliografisk note

© 2019 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Citer dette

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title = "Single-cell high content imaging parameters predict functional phenotype of cultured human bone marrow stromal stem cells",
abstract = "Cultured human bone marrow stromal (mesenchymal) stem cells (hBM-MSCs) are heterogenous cell populations exhibiting variable biological properties. Quantitative high-content imaging technology allows identification of morphological markers at a single cell resolution that are determinant for cellular functions. We determined the morphological characteristics of cultured primary hBM-MSCs and examined their predictive value for hBM-MSC functionality. BM-MSCs were isolated from 56 donors and characterized for their proliferative and differentiation potential. We correlated these data with cellular and nuclear morphological features determined by Operetta; a high-content imaging system. Cell area, cell- and nucleus geometry of cultured hBM-MSCs exhibited significant correlation with expression of hBM-MSC membrane markers: ALP, CD146, CD271. Proliferation capacity correlated negatively with cell and nucleus area and positively with cytoskeleton texture features. In addition, in vitro differentiation to osteoblasts as well as in vivo heterotopic bone formation was associated with decreased ratio of nucleus width to length. Multivariable analysis applying a stability selection procedure identified nuclear geometry and texture as predictors for hBM-MSCs differentiation potential to osteoblasts or adipocytes. Our data demonstrate that by employing a limited number of cell morphological characteristics, it is possible to predict the functional phenotype of cultured hBM-MSCs and thus can be used as a screening test for {"}quality{"} of hBM-MSCs prior their use in clinical protocols. Stem Cells Translational Medicine 2019.",
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AU - Kowal, Justyna M

AU - Schmal, Hagen

AU - Halekoh, Ulrich

AU - Hjelmborg, Jacob B

AU - Kassem, Moustapha

N1 - © 2019 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

PY - 2019/11/23

Y1 - 2019/11/23

N2 - Cultured human bone marrow stromal (mesenchymal) stem cells (hBM-MSCs) are heterogenous cell populations exhibiting variable biological properties. Quantitative high-content imaging technology allows identification of morphological markers at a single cell resolution that are determinant for cellular functions. We determined the morphological characteristics of cultured primary hBM-MSCs and examined their predictive value for hBM-MSC functionality. BM-MSCs were isolated from 56 donors and characterized for their proliferative and differentiation potential. We correlated these data with cellular and nuclear morphological features determined by Operetta; a high-content imaging system. Cell area, cell- and nucleus geometry of cultured hBM-MSCs exhibited significant correlation with expression of hBM-MSC membrane markers: ALP, CD146, CD271. Proliferation capacity correlated negatively with cell and nucleus area and positively with cytoskeleton texture features. In addition, in vitro differentiation to osteoblasts as well as in vivo heterotopic bone formation was associated with decreased ratio of nucleus width to length. Multivariable analysis applying a stability selection procedure identified nuclear geometry and texture as predictors for hBM-MSCs differentiation potential to osteoblasts or adipocytes. Our data demonstrate that by employing a limited number of cell morphological characteristics, it is possible to predict the functional phenotype of cultured hBM-MSCs and thus can be used as a screening test for "quality" of hBM-MSCs prior their use in clinical protocols. Stem Cells Translational Medicine 2019.

AB - Cultured human bone marrow stromal (mesenchymal) stem cells (hBM-MSCs) are heterogenous cell populations exhibiting variable biological properties. Quantitative high-content imaging technology allows identification of morphological markers at a single cell resolution that are determinant for cellular functions. We determined the morphological characteristics of cultured primary hBM-MSCs and examined their predictive value for hBM-MSC functionality. BM-MSCs were isolated from 56 donors and characterized for their proliferative and differentiation potential. We correlated these data with cellular and nuclear morphological features determined by Operetta; a high-content imaging system. Cell area, cell- and nucleus geometry of cultured hBM-MSCs exhibited significant correlation with expression of hBM-MSC membrane markers: ALP, CD146, CD271. Proliferation capacity correlated negatively with cell and nucleus area and positively with cytoskeleton texture features. In addition, in vitro differentiation to osteoblasts as well as in vivo heterotopic bone formation was associated with decreased ratio of nucleus width to length. Multivariable analysis applying a stability selection procedure identified nuclear geometry and texture as predictors for hBM-MSCs differentiation potential to osteoblasts or adipocytes. Our data demonstrate that by employing a limited number of cell morphological characteristics, it is possible to predict the functional phenotype of cultured hBM-MSCs and thus can be used as a screening test for "quality" of hBM-MSCs prior their use in clinical protocols. Stem Cells Translational Medicine 2019.

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