There is increasing awareness that the bone marrow microenvironment is a critical contributor to therapeutic resistance and relapse progression in hematological malignancies. Experimental evidence discussed herein highlights key aspects of the stromal conversion by leukemia and the resulting aberrant signaling within the niche. This article discusses the advantages and limitations of available experimental model system and emphasizes open scientific questions and opportunities.
It remains a challenging era for the clinical development of improved cell therapy strategies for critical limb ischemia (CLI). For the first time, we have the capacity to generate the cells to model complete vessel formation from exogenous allocgeneic and or autologous sources using combinatorial delivery of vessel-forming endothelial precursor cells, with pro-angiogenic hematopoietic progenitor cell, and vessel-stabilizing mesenchymal stem cell, within implantable decellularized matricies in vivo. Unfortunately, the morbidity and mortality from CLI remains unacceptably high and the need for well-controlled translational studies in this area cannot be overemphasized. Thus, careful preclinical evaluation of emerging concepts and technologies are critical for the expedited development of cell therapy trials for CLI.
New research demonstrates how proinflammatory stimuli can promote the production of extracellular vesicles from MSCs with enhanced immunomodulatory capacity.