Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma

Jaehoon Chung; Rajesh Dash; Kehkooi Kee; Joëlle K. Barral; Hisanori Kosuge; Robert C. Robbins; Dwight Nishimura; Renee A. Reijo-Pera; Phillip C. Yang

doi:10.1002/mrm.23262

Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma

Jaehoon Chung, Rajesh Dash, Kehkooi Kee, Joëlle K. Barral, Hisanori Kosuge, Robert C. Robbins, Dwight Nishimura, Renee A. Reijo-Pera, Phillip C. Yang

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn ²⁺) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T₁ shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn²⁺. Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl ₂ intraperitoneally three times a week. The control group was given MnCl₂ only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl₂ enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn²⁺. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

Original language	English (US)
Pages (from-to)	595-599
Number of pages	5
Journal	Magnetic Resonance in Medicine
Volume	68
Issue number	2
DOIs	https://doi.org/10.1002/mrm.23262
State	Published - Aug 2012
Externally published	Yes

Keywords

embryonic stem cell derived teratoma
manganese-enhanced MRI
theranostic effect

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1002/mrm.23262

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title = "Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma",

abstract = "Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn 2+) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T1 shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn2+. Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl 2 intraperitoneally three times a week. The control group was given MnCl2 only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl2 enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn2+. Magn Reson Med, 2012. {\textcopyright} 2011 Wiley Periodicals, Inc.",

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author = "Jaehoon Chung and Rajesh Dash and Kehkooi Kee and Barral, {Jo{\"e}lle K.} and Hisanori Kosuge and Robbins, {Robert C.} and Dwight Nishimura and Reijo-Pera, {Renee A.} and Yang, {Phillip C.}",

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AU - Chung, Jaehoon

AU - Dash, Rajesh

AU - Kee, Kehkooi

AU - Barral, Joëlle K.

AU - Kosuge, Hisanori

AU - Robbins, Robert C.

AU - Nishimura, Dwight

AU - Reijo-Pera, Renee A.

AU - Yang, Phillip C.

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AB - Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn 2+) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T1 shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn2+. Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl 2 intraperitoneally three times a week. The control group was given MnCl2 only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl2 enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn2+. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

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Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma

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