Ex vivo expansion of hematopoietic stem cells: Finally transitioning from the lab to the clinic

Levistilide A Promotes Expansion of Human Umbilical Cord Blood Hematopoietic Stem Cells by Enhancing Antioxidant Activity

“…SR1 is reported to be mostly active on primitive normal hematopoietic progenitors and leukemia stem cells (LSCs) (Fares et al, 2015), while our data showed that LA had superior activity on long-term HSCs. Thus, combining SR1 and LA could make up for the deficiency of LA in expanding HPCs to fulfill complete proliferation of UCB-derived cells, even if the combination of LA and SR1 did not achieve expected combined effect on some type of colony and engraftment capacity, which is consistent with previous studies that show synergistic effect of the combination of SR1 and UM171 merely restricted to progenitor cell subpopulation (Zimran et al, 2021). This phenomenon reminds us that a combination of various agents with stem cell activity may lead to senescence or simply prove redundant.…”

“…To overcome the aforementioned obstacles, various strategies of expanding HSPCs ex vivo have been tested in the laboratory and even in the clinic, including genetic or epigenetic operations, modified culture systems with distinct combinations of cytokines such as stem cell factor (SCF), FMS-like tyrosine kinase-3 ligand (FLT3-L), and thrombopoietin (TPO), and also small molecules targeting certain signaling pathways (Zimran et al, 2021). However, small molecules show more advantages in aspects of safety, operational feasibility, expansion efficiency, and economy (Zhang et al, 2012).…”

“…As exemplified by the surprising successes demonstrated for StemRegenin 1 (SR1) and UM171, the potential of small molecules to expand HSPCs has gradually been tapped. Ex vivo expansion by small molecules can either improve the homing of engrafted HSPCs (Christopherson et al, 2007;Goessling et al, 2011) or expand the absolute number of HSPCs in UCB collections (Fares et al, 2015;Zimran et al, 2021). SR1 (Boitano et al, 2010) and UM171 (Fares et al, 2014) are two potent small molecules that can preferentially expand hematopoietic progenitor cells (HPCs) and long-term HSCs, respectively, ex vivo.…”

Hematopoiesis during Ontogenesis, Adult Life, and Aging

“…No statistically significant differences with control were observed for recipient survival and graft-versus-host disease (GvHD) [221]. Current studies on ex vivo expansion of HSCs and the available results of clinical trials are described in more detail in a recent review by Zimran et al [222]. It should also be noted that the successful expansion of long-term engrafting HSCs from UCB paves the way to development of advanced strategies of HSCs-based gene therapy using DNA-integrating vectors or genome editing.…”

Recent Advances in Developmental Hematopoiesis: Diving Deeper With New Technologies

“…The increased number of diseases and disorders treated at least in part by HSC transplantations and the difficulties to find HSCs with the best donor-patient compatibility is a major issue. Decades of efforts to develop culture conditions, either to expand HSCs ex vivo or to generate new HSCs in vitro, hold great promise but success remains limited (10)(11)(12)(13). The low production of HSC-like cells with limited multilineage and/or self-renewal properties remains a major barrier to a successful use of HSCs for transplantation and gene modification.…”