Microenvironment and multiple myeloma spread.

Thromb Res

Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy. Electronic address:

Published: May 2014

In patients with multiple myeloma (MM), the bone marrow (BM) contains hematopoietic stem cells (HSCs) and non-hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes mesenchymal stem cells (MSCs), fibroblasts, osteoblasts, osteoclasts, chondroclasts, endothelial cells, endothelial progenitor cells (EPCs), B and T lymphocytes, NK cells, erythrocytes, megakaryocytes, platelets, macrophages and mast cells. All of these cells form specialized "niches" in the BM microenvironment which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular niche" is rich in blood vessels where endothelial cells and mural cells (pericytes and smooth muscle cells) create a microenvironment that affects the behavior of several stem and progenitor cells. The vessel wall serves as an independent niche for the recruitment of endothelial progenitor cells, MSCs and HSCs. The activation by angiogenic factors and inflammatory cytokines switch the "vascular niche" to promote MM tumor growth and spread. This review will focus on the mechanisms involved in the generation of signals released by endothelial cells in the "vascular niche" that promote tumor growth and spread in MM.

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http://dx.doi.org/10.1016/S0049-3848(14)50017-5DOI Listing

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Article Synopsis
  • - Current hematology studies often use immunodeficient mouse models to test patient-derived stem cells, but these models struggle with effectively incorporating cells from patients with myelodysplastic syndromes (MDS).
  • - Researchers created a new bone marrow organoid model from induced pluripotent stem cells (iPSCs) that accurately mimics the human bone marrow environment, improving the engraftment of MDS patient stem cells and reflecting their unique disease traits.
  • - The organoid model demonstrated that stem cells from both normal donors and MDS patients could proliferate and maintain their characteristics in a supportive microenvironment, revealing distinct differentiation patterns that correlate with MDS's clinical features and opening up possibilities for personalized treatments.
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Article Synopsis
  • There is a need for therapies to address bone marrow dysfunction and organ toxicity following myeloablative injury during bone marrow transplantation (BMT), associated with damage to the vascular endothelium and other organs.* -
  • The study aimed to assess the effects of the thrombopoietin mimetic drug JNJ-26366821 (TPOm) on the recovery of bone marrow vascularity in mice undergoing BMT after receiving radiation conditioning.* -
  • Results indicated that while donor chimerism remained similar in TPOm and control-treated mice, the treatment enhanced bone marrow vasculature regeneration, showing dose-dependent improvements in microvascular density and other vascular metrics on day 14 post-BMT.*
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