Substrate and culture technologies for mimicking the bone marrow niche: towards ex-vivo expansion of hematopoietic stem cells

Abstract

Hematopoietic stem cells (HSCs) are a rare bone marrow cell population is capable of differentiating into every blood cell, including immune cells, in the human body. This makes them extremely valuable clinical therapies for diseases of the blood, including anemia, myeloma, and leukemia, for which transplantation of HSCs can constitute a cure. As such, many researchers have sought to expand HSCs ex-vivo in order to avoid the limitations of donor bone marrow transplantation. However, the tendency of HSCs to differentiate in improper culture conditions makes inducing or maintaining their self-renewal a significant challenge. Physical and chemical stimuli affect HSC behavior, which can include fluid shear, extracellular matrix composition, paracrine and autocrine signaling, and nutrient density, as well as the patterns and combinations therein. In an effort to recapitulate the niches of HSCs in-vitro, researchers have experimented with many technologies to create different substrate materials, complex culture systems, and gradient patterning for the efficient support and expansion of HSCs. In this review, substrate and culture technologies from recent years are analyzed through the lens of their potential for ex-vivo HSC expansion with the aim of informing future research.