Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry

Si Yeon Lee, Sangmin Lee, Jangwook Lee, Ji Young Yhee, Hwa In Yoon, Soon Jung Park, Heebeom Koo, Sung Hwan Moon, Hyukjin Lee, Yong Woo Cho, Sun Woong Kang, Sangyup Lee, Kwangmeyung Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Labeling of stem cells aims to distinguish transplanted cells from host cells, understand in vivo fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the in vivo evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track in vivo fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases.

Original languageEnglish
Pages (from-to)779-786
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume479
Issue number4
DOIs
Publication statusPublished - 2016 Oct 28

Fingerprint

Cell Tracking
Click Chemistry
Hindlimb
Stem cells
Copper
Animals
Stem Cells
Ischemia
Animal Models
Labeling
Azides
Mesenchymal Stromal Cells
Optical Devices
Optical Imaging
Tissue regeneration
Therapeutic Uses
Cell- and Tissue-Based Therapy
Regeneration
Glycoproteins
Imaging systems

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Si Yeon ; Lee, Sangmin ; Lee, Jangwook ; Yhee, Ji Young ; Yoon, Hwa In ; Park, Soon Jung ; Koo, Heebeom ; Moon, Sung Hwan ; Lee, Hyukjin ; Cho, Yong Woo ; Kang, Sun Woong ; Lee, Sangyup ; Kim, Kwangmeyung. / Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 479, No. 4. pp. 779-786.
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abstract = "Labeling of stem cells aims to distinguish transplanted cells from host cells, understand in vivo fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the in vivo evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track in vivo fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases.",
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Lee, SY, Lee, S, Lee, J, Yhee, JY, Yoon, HI, Park, SJ, Koo, H, Moon, SH, Lee, H, Cho, YW, Kang, SW, Lee, S & Kim, K 2016, 'Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry', Biochemical and Biophysical Research Communications, vol. 479, no. 4, pp. 779-786. https://doi.org/10.1016/j.bbrc.2016.09.132

Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry. / Lee, Si Yeon; Lee, Sangmin; Lee, Jangwook; Yhee, Ji Young; Yoon, Hwa In; Park, Soon Jung; Koo, Heebeom; Moon, Sung Hwan; Lee, Hyukjin; Cho, Yong Woo; Kang, Sun Woong; Lee, Sangyup; Kim, Kwangmeyung.

In: Biochemical and Biophysical Research Communications, Vol. 479, No. 4, 28.10.2016, p. 779-786.

Research output: Contribution to journalArticle

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T1 - Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry

AU - Lee, Si Yeon

AU - Lee, Sangmin

AU - Lee, Jangwook

AU - Yhee, Ji Young

AU - Yoon, Hwa In

AU - Park, Soon Jung

AU - Koo, Heebeom

AU - Moon, Sung Hwan

AU - Lee, Hyukjin

AU - Cho, Yong Woo

AU - Kang, Sun Woong

AU - Lee, Sangyup

AU - Kim, Kwangmeyung

PY - 2016/10/28

Y1 - 2016/10/28

N2 - Labeling of stem cells aims to distinguish transplanted cells from host cells, understand in vivo fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the in vivo evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track in vivo fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases.

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