Noninvasive MRI and multilineage differentiation capability of ferritin-transduced human mesenchymal stem cells

Hoe Suk Kim, Jisu Woo, Yoonseok Choi, Eun Hye Hwang, Sul Ki Choi, Kyoung Won Cho, Woo Kyung Moon

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Molecular imaging can be a breakthrough tool for the investigation of the behavior and ultimate feasibility of transplanted human mesenchymal stem cells (hMSCs) inside the body, and for the development of guidelines and recommendations based on the treatment and evaluation of stem cell therapy for patients. The goals of this study were to evaluate the multilineage differentiation ability of hMSCs expressing an MRI reporter, human ferritin heavy chain (FTH) and to investigate the feasibility of using FTH-based MRI to provide noninvasive imaging of transplanted hMSCs. The transduction of FTH and green fluorescence protein (GFP) did not influence the expression of the mesenchymal stem cell surface markers (CD29+/CD105+/CD34-/CD45-) or the self-renewal marker genes [octamer-binding transcription factor 4 (OCT-4) and SRY (sex determining region Y)-box 2 (Sox-2)], cell viability, migration ability and the release of cytokines [interleukin-5 (IL-5), IL-10, IL-12p70, tumor necrosis factor-α (TNF-α)]. FTH-hMSCs retained the capacity to differentiate into adipogenic, chondrogenic, osteogenic and neurogenic lineages. The transduction of FTH led to a significant enhancement in cellular iron storage capacity and caused hypointensity and a significant increase in R2* values of FTH-hMSC-collected phantoms and FTH-hMSC-transplanted sites of the brain, as shown by in vitro and in vivo MRI performed at 9.4T, compared with control hMSCs. This study revealed no differences in biological characteristics between hMSCs and FTH-hMSCs and, therefore, these cells could be used for noninvasive monitoring with MRI during stem cell therapy for brain injury. Our study suggests the use of FTH for in vivo long-term tracking and ultimate fate of hMSCs without alteration of their characteristics and multidifferentiation potential.

Original languageEnglish
Pages (from-to)168-179
Number of pages12
JournalNMR in Biomedicine
Volume28
Issue number2
DOIs
StatePublished - 1 Feb 2015

Fingerprint

Apoferritins
Ferritins
Stem cells
Mesenchymal Stromal Cells
Magnetic resonance imaging
Aptitude
Cell- and Tissue-Based Therapy
Octamer Transcription Factors
Stem Cells
Brain
Molecular Imaging
Interleukin-5
Molecular imaging
Interleukin-10
Brain Injuries
Cell Movement
Cell Survival
Iron
Tumor Necrosis Factor-alpha
Fluorescence

Keywords

  • Ferritin
  • Human mesenchymal stem cell
  • MRI
  • Multilineage differentiation
  • Stem cell therapy
  • in vivo tracking

Cite this

Kim, Hoe Suk ; Woo, Jisu ; Choi, Yoonseok ; Hwang, Eun Hye ; Choi, Sul Ki ; Cho, Kyoung Won ; Moon, Woo Kyung. / Noninvasive MRI and multilineage differentiation capability of ferritin-transduced human mesenchymal stem cells. In: NMR in Biomedicine. 2015 ; Vol. 28, No. 2. pp. 168-179.
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Noninvasive MRI and multilineage differentiation capability of ferritin-transduced human mesenchymal stem cells. / Kim, Hoe Suk; Woo, Jisu; Choi, Yoonseok; Hwang, Eun Hye; Choi, Sul Ki; Cho, Kyoung Won; Moon, Woo Kyung.

In: NMR in Biomedicine, Vol. 28, No. 2, 01.02.2015, p. 168-179.

Research output: Contribution to journalArticle

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AU - Kim, Hoe Suk

AU - Woo, Jisu

AU - Choi, Yoonseok

AU - Hwang, Eun Hye

AU - Choi, Sul Ki

AU - Cho, Kyoung Won

AU - Moon, Woo Kyung

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AB - Molecular imaging can be a breakthrough tool for the investigation of the behavior and ultimate feasibility of transplanted human mesenchymal stem cells (hMSCs) inside the body, and for the development of guidelines and recommendations based on the treatment and evaluation of stem cell therapy for patients. The goals of this study were to evaluate the multilineage differentiation ability of hMSCs expressing an MRI reporter, human ferritin heavy chain (FTH) and to investigate the feasibility of using FTH-based MRI to provide noninvasive imaging of transplanted hMSCs. The transduction of FTH and green fluorescence protein (GFP) did not influence the expression of the mesenchymal stem cell surface markers (CD29+/CD105+/CD34-/CD45-) or the self-renewal marker genes [octamer-binding transcription factor 4 (OCT-4) and SRY (sex determining region Y)-box 2 (Sox-2)], cell viability, migration ability and the release of cytokines [interleukin-5 (IL-5), IL-10, IL-12p70, tumor necrosis factor-α (TNF-α)]. FTH-hMSCs retained the capacity to differentiate into adipogenic, chondrogenic, osteogenic and neurogenic lineages. The transduction of FTH led to a significant enhancement in cellular iron storage capacity and caused hypointensity and a significant increase in R2* values of FTH-hMSC-collected phantoms and FTH-hMSC-transplanted sites of the brain, as shown by in vitro and in vivo MRI performed at 9.4T, compared with control hMSCs. This study revealed no differences in biological characteristics between hMSCs and FTH-hMSCs and, therefore, these cells could be used for noninvasive monitoring with MRI during stem cell therapy for brain injury. Our study suggests the use of FTH for in vivo long-term tracking and ultimate fate of hMSCs without alteration of their characteristics and multidifferentiation potential.

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