Route of del ivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

Fang Jing Wang, Saada Eid, James E. Dennis, Kenneth R Cooke, Jeffery J. Auletta, Zhenghong Lee

Research output: Contribution to journalArticle

Abstract

Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole-body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

Original languageEnglish (US)
Pages (from-to)P34-P43
JournalJournal of Stem Cells and Regenerative Medicine
Volume11
Issue number2
StatePublished - 2015

Fingerprint

Bone Marrow Transplantation
Mesenchymal Stromal Cells
Homologous Transplantation
Bone
Bioluminescence
Bone Marrow
Imaging techniques
Tail
Veins
Technetium Tc 99m Exametazime
Lung
Injections
Graft vs Host Disease
Luciferases
Transplants
Reporter Genes
Carotid Arteries
Radionuclide Imaging
Grafts
Transplantation

Keywords

  • Arterial injection
  • Biodistribution
  • Graft-versus-host disease
  • Mesenchymal stromal cell
  • Radionuclide imaging

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Cell Biology

Cite this

Route of del ivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation. / Wang, Fang Jing; Eid, Saada; Dennis, James E.; Cooke, Kenneth R; Auletta, Jeffery J.; Lee, Zhenghong.

In: Journal of Stem Cells and Regenerative Medicine, Vol. 11, No. 2, 2015, p. P34-P43.

Research output: Contribution to journalArticle

@article{740efcaf2673489aafffabcfbfcda0e3,
title = "Route of del ivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation",
abstract = "Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole-body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.",
keywords = "Arterial injection, Biodistribution, Graft-versus-host disease, Mesenchymal stromal cell, Radionuclide imaging",
author = "Wang, {Fang Jing} and Saada Eid and Dennis, {James E.} and Cooke, {Kenneth R} and Auletta, {Jeffery J.} and Zhenghong Lee",
year = "2015",
language = "English (US)",
volume = "11",
pages = "P34--P43",
journal = "Journal of Stem Cells and Regenerative Medicine",
issn = "0973-7154",
publisher = "Nichi-Hepz Kenko (NHK) Services Private Limited",
number = "2",

}

TY - JOUR

T1 - Route of del ivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

AU - Wang, Fang Jing

AU - Eid, Saada

AU - Dennis, James E.

AU - Cooke, Kenneth R

AU - Auletta, Jeffery J.

AU - Lee, Zhenghong

PY - 2015

Y1 - 2015

N2 - Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole-body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

AB - Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole-body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

KW - Arterial injection

KW - Biodistribution

KW - Graft-versus-host disease

KW - Mesenchymal stromal cell

KW - Radionuclide imaging

UR - http://www.scopus.com/inward/record.url?scp=84952764986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952764986&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:84952764986

VL - 11

SP - P34-P43

JO - Journal of Stem Cells and Regenerative Medicine

JF - Journal of Stem Cells and Regenerative Medicine

SN - 0973-7154

IS - 2

ER -