Review: Biomimetic nanofibers in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Abstract

This review summarizes current strategies in the development of advanced nanofibrous polymer-based scaffolds via electrospinning, their applications in mimicking the extracellular matrix, and the use of polymer nanofibers to deliver growth factors or small molecules for ex vivo expansion of HSCs. Hematopoietic stem cell (HSC) transplantation has become the standard of care for patients with hematologic cancers, anemia, and a variety of other malignant and non-malignant disorders. Although mobilized peripheral blood (MPB) has become a preferred source of HSCs for transplants, bone marrow (BM) and umbilical cord blood (UCB) are also frequently utilized. Regardless of source, Regardless of source, HSC transplantation suffers from low cell doses. Therefore, methods to increase the cell dose while maintaining the progenitor phenotype, especially the CD34+ progenitor cells, would have a significant clinical impact. Ex vivo expansion of HSCs prior to transplantation is one approach that offers tremendous promise for increasing cell doses and improving clinical outcomes. Many ex vivo strategies have been developed within the last decade in order to address the issue of low cell dose, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Here, we report the current progress of nanofibrous scaffolds for the ex vivo expansion of hematopoietic stem cells (HSCs). In this review, we present the technique of electrospinning for nanofibrous scaffolds, focusing mainly on preparation methods, materials (synthetic, natural, and hybrid polymers), and surface-structural modifications. The variables of nanofiber processing parameters and its impact on the nanofiber assembly is reported as well as the effect of the solution parameters on the structural morphology of the fabricated nanofibers. Critical features of fabricated nanofibers such as porous structure and high specific surface area are addressed, but more importantly the necessity of mimicking the intrinsic properties of the native in vivo microenvironment of the extracellular matrix (ECM). Researchers have been largely successful in replicating the diverse nature of the ECM through the incorporation of small molecules, growth factors, and signaling molecules into 3D scaffolds to generate biomimetic hierarchical structures. Harnessing the potential of the stem cell niche forms the basis of clinical therapy in the ex vivo expansion of cord blood-derived hematopoietic stem cells. As reviewed in this article, advances in nanofiber ex vivo approaches based upon emerging biomaterials opens new doors for artificial niches. Scientific evidence provided in this review verifies that the nanofiber niche provides an ideal mimic of the physical microenvironment of HSCs thereby offering great potential for clinical applications.