Int J Biol Macromol. 2026 Jan;339(Pt 2):149957. doi: 10.1016/j.ijbiomac.2025.149957. Epub 2025 Dec 29.
ABSTRACT
With the advancement of regenerative medicine and precision healthcare, ex vivo expansion of hematopoietic stem cells (HSCs) holds significant promise for clinical transplantation, gene therapy, and drug screening. However, achieving large-scale expansion while preserving stemness and long-term repopulating capacity remains a substantial challenge. This review summarizes recent advances in multimodal strategies for HSCs expansion from both molecular and engineering perspectives, with a particular emphasis on biomacromolecular regulation. At the molecular level, we discuss how cytokines and stromal cell co-culture systems mediate niche-derived biomacromolecular signals that preserve HSCs stemness. At the engineering level, we emphasize recent modifications in biomaterial structures, such as porous scaffolds, nanofibers, and hydrogels-that improve the presentation and delivery of biomacromolecular cues. These innovations significantly improve the precision and scalability of HSCs expansion. We further examine bioreactor systems that regulate microenvironmental conditions and molecular gradients to support consistent, large-scale expansion. We propose an integrated evaluation framework that combines ex vivo and in vivo biomacromolecular readouts to assess stemness preservation and translational potential of expanded HSCs. Future expansion platforms are expected to integrate smart biomaterials, artificial intelligence, and organ-on-a-chip technologies to enable programmable control of biomacromolecular signaling. These advances may help overcome current limitations in efficiency, consistency, and cost, ultimately providing customizable clinical-grade HSCs products.
PMID:41475650 | DOI:10.1016/j.ijbiomac.2025.149957