Challenges and Opportunities to Harnessing the (Hematopoietic) Stem Cell Niche

In our body, stem cells reside in a microenvironment termed the niche. While the exact composition and, therefore, the level of complexity of a stem cell niche can vary significantly tissue-to-tissue, the stem cell niche microenvironment is dynamic, typically containing spatial and temporal variations in both cellular, extracellular matrix, and biomolecular components. This complex flow of secreted or bound biomolecules, cytokines, extracellular matrix components, and cellular constituents all contributes to the regulation of stem cell fate specification events, making engineering approaches at the nanoscale and microscale of particular interest for creating an artificial niche environment in vitro. Recent advances in fabrication approaches have enabled biomedical researchers to capture and recreate the complexity of stem cell niche microenvironments in vitro. Such engineered platforms show promise as a means to enhance our understanding of the mechanisms underlying niche-mediated stem cell regulation as well as offer opportunities to precisely control stem cell expansion and differentiation events for clinical applications. While these principles generally apply to all adult stem cells and niches, in this review, we focus on recent developments in engineering synthetic niche microenvironments for one of the best-characterized stem cell populations, hematopoietic stem cells (HSCs). Specifically, we highlight recent advances in platforms designed to facilitate the extrinsic control of HSC fate decisions.