Artificial Niches: Biomimetic Materials for Hematopoietic Stem Cell Culture

Abstract

Hematopoietic stem cells (HSCs) are indispensable for the treatment of patients with hematological disorders such as leukemia. However, the amount of available transplantable HSCs is limited. Therefore, new approaches to multiply HSCs in the laboratory are needed. Promising biomimetic technologies for HSC expansion are currently developed. This feature article gives an insight into the significance of this approach and introduces the essential building blocks (cells, matrix, and scaffolds) of biomimetic materials. Some recent strategies are highlighted and the challenges and possible applications of such materials are discussed.

Biophysical regulation of hematopoietic stem cells

“…Cells are able to integrate these different signals and to respond specifically to nanostructural features of their environment. 47,67 In order to investigate the impact of nanometer scale distances between specific adhesive ligands on cellular behaviour, nanopatterned substrates were developed that allow the positioning of ligands with precision in the nanometer range. Using block-copolymer micellar nanolithography, gold nanoparticles with a typical diameter of less than 10 nm were deposited on glass or silicium substrates in a quasi-hexagonal order.…”

Cardiac stem cell niches

“…A well-defined growth medium supplemented with specific cytokines and the presence of feeder layers are often required for the maintenance of the undifferentiated state of stem cells. More recently, attempts have been made to develop artificial niches able to protect the immature stem cell phenotype (Lee-Thedieck and Spatz, 2012; Tan and Barker, 2013 ).…”

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

“…These unique regions – niches – offer exciting opportunities to develop new bioengineering approaches that use nano- and micro-scale technologies to engineer cell fate [1, 5, 6]. An increasing number of adult stem cells and their corresponding niches have been identified in different tissues and organs, including skin, gut, bone marrow, and brain [7–13].…”

“…Identifying the role played by biophysical and molecular features of the niche on HSC fate specification requires new tools to examine and control these processes ex vivo [1]. Bioengineering approaches may be particularly well suited to reduce the complexity of the niche to gain mechanistic insight regarding how the biophysical and molecular signal pathways shape HSC fate [1, 5, 6, 33]. Though improved understanding of how the niche modulates complex stem cell behaviors, we can eventually gain the capacity to engineer stem cell fate decisions in vitro [6, 34–37].…”

“…The paucity of stem cells, however, requires our ability to precisely control their activities in vitro, particularly expansion and differentiation, in order to increase their potential clinical value [1, 44, 45]. Since multiple niche constituents have been shown previously to modulate stem cell behaviors, biomedical researchers in the field have been trying to recreate aspects of stem cell niche microenvironments in vitro to better understand niche-mediated stem cell regulation as well as to better manipulate stem cell functions [5, 6, 34, 44]. While this approach has led to some creative means to expand or differentiate stem cells and new insights into stem cell maintenance, current technical limitations make it challenging to recapitulate the complexity of the niche architecture in vitro [1, 5, 6, 34, 36, 37, 44].…”