Engineering the hematopoietic stem cell niche: Frontiers in biomaterial science

Abstract

Hematopoietic stem cells (HSCs) play a crucial role in the generation of the body’s blood and immune cells. This process takes place primarily in the bone marrow in specialized ‘niche’ microenvironments, which provide signals responsible for maintaining a balance between HSC quiescence, self-renewal, and lineage specification required for life-long hematopoiesis. While our understanding of these signaling mechanisms continues to improve, our ability to engineer them in vitro for the expansion of clinically relevant HSC populations is still lacking. In this review, we focus on development of biomaterials-based culture platforms for in vitro study of interactions between HSCs and their local microenvironment. The tools and techniques used for both examining HSC-niche interactions as well as applying these findings towards controlled HSC expansion or directed differentiation in 2D and 3D platforms are discussed. These novel techniques hold the potential to push the existing boundaries of HSC cultures towards high-throughput, real-time, and single-cell level biomimetic approaches that enable a more nuanced understanding of HSC regulation and function. Their application in conjunction with innovative biomaterial platforms can pave the way for engineering artificial bone marrow niches for clinical applications as well as elucidating the pathology of blood-related cancers and disorders.

Mesenchymal stromal cell remodeling of a gelatin hydrogel microenvironment defines an artificial hematopoietic stem cell niche

“…The LSK faction was collect in PBS + 25% FBS on ice and immediately used [19,29,46,[67][68][69][70].…”

Artificial Hematopoietic Stem Cell Niches-Dimensionality Matters

“…Moreover, mouse and human niches differ in some respects so that the cellular composition of artificial niches realizable in the mouse setting may not be transferable to the human situation. In addition, the extracellular matrix composition influences HSC differentiation, proliferation, lineage specification, and apoptosis [63][64][65][66]. The materials used in studies are therefore of utmost importance, and, as has been shown for some materials, may not be suitable for the in vitro culture of CD34 + cells [67].…”

Concise Review: Recent Advances in the In Vitro Derivation of Blood Cell Populations

“…Collectively, these findings clearly demonstrate the importance of cell, matrix, and molecular cues from the endogenous niche in providing functionality to HSCs. Recent advances in tissue engineering to mimic the bone marrow niche showed promising, yet not conclusive, methods to maintain HSCs derived from bone marrow or cord blood [75]. Future efforts to mimic the authentic milieu of cell, matrix, and biomolecule cues by integrating novel tissue engineering approaches will be useful to maintain and expand HSCs.…”