Hematopoietic Stem Cell–Derived Pericytic Cells in Brain Tumor Angio-Architecture

Abstract

Bone marrow-derived cells are recruited into tumor vasculature in response to angiogenic signals, and some of the cells within the newly forming tumor vessels are hematopoietic stem cells (HSCs) in origin. Previous studies suggest that bone marrow-derived pericytes are associated with newly formed vessels in tumors. In this study, we used an orthotopic rat glioma model (RT-2/RAG) to examine the contribution of long-term hematopoietic stem cell (LT-HSC)-derived pericytic cells to brain tumor angiogenesis. Mice (RAG-2/KO5.2) were lethally irradiated, and their hematopoietic cells were repopulated by transplantation of double fluorescence-activated cell-sorted LT-HSCs that express green fluorescent protein (GFP+). RT-2/RAG cells were then injected into the striatum of the chimeric mice 6 weeks post-transplantation. The animals were sacrificed 9 days after tumor implantation, and the incorporation and lineage-specific marker expression profile of the GFP+ cells within the growing tumor and tumor periphery were analyzed. LT-HSC-derived GFP+ cells were noted to incorporate onto the surface of tumor vessels within the perivascular space. LT-HSC-derived GFP+ cells express the pericyte progenitor marker, platelet-derived growth factor receptor-beta (PDGFR beta), as well as mature perictyte markers such as nerve/glial antigen 2 proteoglycan (NG2), alpha-smooth muscle actin (alpha SMA), and desmin. These LT-HSC-derived cells may represent a population of progenitor or committed pericytes within the neovascular tree and may play a role in shaping the angio-architecture in the vascular niche of brain tumors.

Glioma tropism of lentivirally transduced hematopoietic progenitor cells

“…Endogenous bone marrow-derived cells have been detected in experimental gliomas (34). To analyze the influence of lentiviral transduction on the glioma-mediated attraction of bone marrow-derived cells, we performed bone marrow reconstitutions.…”

Cancer gene therapy using mesenchymal stem cells

“…Endothelial cells (ECs), pericytes, and stromal cells are all known to support tumor growth and contribute to the tumor microenvironment by producing various growth factors including vascular endothelial growth factor (VEGF)-A, IL-8, transforming growth factor (TGF)-b, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) [24][25][26][27][28][29]. MSCs can also act in such a supportive fashion.…”

Clinical Trials of Adult Stem Cell Therapy for Peripheral Artery Disease

“…15,16 additionally, other bone marrow-derived cells, such as pericytes, can associate with and stabilize endothelial networks. 17 it is possible that a greater effect and/or more persistent benefit of cell therapy could be realized with a more precisely defined cell population. additionally, it is not known what combination of progenitor cells might be most therapeutic in humans, e.g., purified ePCs or some combination with smooth muscle or other precursors and/or subsets of hematopoietic progenitors.…”