From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier?

Liu, Linan; Eckert, Mark A.; Riazifar, Hamidreza; Kang, Dong‐Ku; Agalliu, Dritan; Zhao, Weian

doi:10.1155/2013/435093

Cited by 105 publications

(106 citation statements)

References 65 publications

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“…MSCs have natural stealth properties and are able to cross biologic barriers. 52,53 Thus, MSCs hold a tremendous potential for being employed in anticancer therapy as drug delivery vehicles. In addition, nanoparticle-labeled MSC homing to cancerous tissue would add great benefit to visualization of tumors and/or metastases and their response to treatment.…”

Section: Discussionmentioning

confidence: 99%

“…A considerable amount of research has been done on glioma models, as MSCs are able to cross the blood-brain barrier and localize in intracranial neoplasms. 20,53,62 Adipose tissue-or bone marrow-derived MSCs are most commonly used in tumor-tropic cell therapy researches. To our knowledge, we are the first ones to use skin connective tissue MSCs for tumor-tropic nanoparticle delivery.…”

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confidence: 99%

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Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dapkutė¹,

Steponkienė²,

Bulotienė³

et al. 2017

IJN

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Purpose Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs). Materials and methods Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used. Results QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver). Conclusion Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dapkutė¹,

Steponkienė²,

Bulotienė³

et al. 2017

IJN

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“…Therefore, the exact mechanisms to explain how MSCs actively cross the BBB remain to be determined. 39 To understand the fate of transplanted MSCs in vivo, noninvasive imaging techniques are needed to monitor the …”

Section: Discussionmentioning

confidence: 99%

In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution

Kim

Jeong

Woo

et al. 2015

IJN

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Mesenchymal stem cell (MSC)-based gene therapy is a promising tool for the treatment of various neurological diseases, including brain tumors. However, the tracking of in vivo stem cell migration, distribution, and survival need to be defined for their clinical application. The systemic routes of stem cell delivery must be determined because direct intracerebral injection as a cure for brain tumors is an invasive method. In this study, we show for the first time that near-infrared (NIR) imaging can reveal the distribution and tumor tropism of intravenously injected MSCs in an intracranial xenograft glioma model. MSCs were labeled with NIR fluorescent nanoparticles, and the effects of the NIR dye on cell proliferation and migratory capacity were evaluated in vitro. We investigated the tumor-targeting properties and tissue distribution of labeled MSCs introduced by intravenous injection and followed by in vivo imaging analysis, histological analysis, and real-time quantitative polymerase chain reaction. We observed no cytotoxicity or change in the overall growth rate and characteristics of labeled MSCs compared with control MSCs. NIR fluorescent imaging showed the organ distribution and targeted tumor tropism of systemically injected human MSCs. A significant number of MSCs accumulated specifically at the tumor site in the mouse brain. These results suggest that NIR-based cell tracking is a potentially useful imaging technique to visualize cell survival, migration, and distribution for the application of MSC-mediated therapies in the treatment of malignant gliomas.

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“…Implantation of rodent or human MSCs by different means, including systemically and by intracerebral transplantation, several hours to days after cerebral ischemia has been shown to reduce infarct size and improve neurological function in rodent ischemia stroke models through its neurorestorative and neuroprotective effects. 5,6,7 MSCs delivered systemically (intravenously or intra-arterially) can pass the blood-brain barrier (BBB), enter the brain, and localize to sites of injury, inflammation, and ischemia in spite of that most of them are stuck in the lung vasculature. 5,6 Kim et al 8 had confirmed MSCs' brain tropism by performing whole-body imaging of radiolabeled human adipose-derived MSCs systemically given to rats with middle cerebral artery occlusion (MCAO).…”

Section: Introductionmentioning

confidence: 99%

“…5,6,7 MSCs delivered systemically (intravenously or intra-arterially) can pass the blood-brain barrier (BBB), enter the brain, and localize to sites of injury, inflammation, and ischemia in spite of that most of them are stuck in the lung vasculature. 5,6 Kim et al 8 had confirmed MSCs' brain tropism by performing whole-body imaging of radiolabeled human adipose-derived MSCs systemically given to rats with middle cerebral artery occlusion (MCAO). MSCs were trapped in the lungs for the first 2 hours after stroke onset but continued migrating over time to be found within the region of ischemic lesions.…”

Section: Introductionmentioning

confidence: 99%