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Review
. 2021 Nov 24:14:749716.
doi: 10.3389/fnmol.2021.749716. eCollection 2021.

Treating Metastatic Brain Cancers With Stem Cells

Nadia Sadanandan  1 , Alex Shear  2 , Beverly Brooks  3 , Madeline Saft  4 , Dorothy Anne Galang Cabantan  5 , Chase Kingsbury  3 , Henry Zhang  2 , Stefan Anthony  6 , Zhen-Jie Wang  3 , Felipe Esparza Salazar  7 , Alma R Lezama Toledo  7 , Germán Rivera Monroy  7 , Joaquin Vega Gonzales-Portillo  8 , Alexa Moscatello  3 , Jea-Young Lee  3 , Cesario V Borlongan  3   9
Affiliations
Review

Treating Metastatic Brain Cancers With Stem Cells

Nadia Sadanandan et al. Front Mol Neurosci. .

Abstract

Stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. Here we posit the critical role of a leaky blood-brain barrier (BBB) as a key element for the development of brain metastases, specifically melanoma. By reviewing the immunological and inflammatory responses associated with BBB damage secondary to tumoral activity, we identify the involvement of this pathological process in the growth and formation of metastatic brain cancers. Likewise, we evaluate the hypothesis of regenerating impaired endothelial cells of the BBB and alleviating the damaged neurovascular unit to attenuate brain metastasis, using the endothelial progenitor cell (EPC) phenotype of bone marrow-derived mesenchymal stem cells. Specifically, there is a need to evaluate the efficacy for stem cell therapy to repair disruptions in the BBB and reduce inflammation in the brain, thereby causing attenuation of metastatic brain cancers. To establish the viability of stem cell therapy for the prevention and treatment of metastatic brain tumors, it is crucial to demonstrate BBB repair through augmentation of vasculogenesis and angiogenesis. BBB disruption is strongly linked to metastatic melanoma, worsens neuroinflammation during metastasis, and negatively influences the prognosis of metastatic brain cancer. Using stem cell therapy to interrupt inflammation secondary to this leaky BBB represents a paradigm-shifting approach for brain cancer treatment. In this review article, we critically assess the advantages and disadvantages of using stem cell therapy for brain metastases and glioblastoma.

Keywords: blood brain barrier; bone marrow derived mesenchymal stem cell; brain metastases; endothelial progenitor cell; melanoma; neuroinflammation; stem cell therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The barriers in stem cell therapy for brain cancers. Cancer cells in the brain circumvent the host immune surveillance, in part, due to their own tumor barrier. (A) Inflammation that accompanies cancer cell infiltration may compromise BBB permeability, allowing inflammatory cells to penetrate the brain and exacerbate tumorigenesis. (B) Stem cell therapy directed at repairing the BBB may prevent the influx of deleterious inflammatory cells into the brain and cancer cells and improve the surrounding environment. However, stem cells may also facilitate the potency of tumor barrier, allowing angiogenic and vasculogenic support to the cancer cells thereby aiding in tumorigenesis. Such risk-to-benefit outcome warrants a careful examination of advancing stem cell therapy for cancer treatment.
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