Scoping Review of Factors Associated with Stem Cell Mobilization and Collection in Allogeneic Stem Cell Donors.

There is wide interindividual variation in the efficacy of CD34+ cell mobilization and collection in healthy allogenic hematopoietic stem cell donors. Donor characteristics, blood cell counts, and various factors related to mobilization and collection have been associated with blood CD34+ cell count and CD34+ cell yield after granulocyte colony-stimulating factor (G-CSF) mobilization and collection. Given the heterogenous nature of the literature reporting these associations, in this scoping review we clarify the determinants of CD34+ count and yield. Studies published between 2000 and 2023 reporting allogeneic donors undergoing G-CSF mobilization and peripheral blood stem cell (PBSC) collection were evaluated. Eligible studies were those that assessed blood CD34+ cell count or CD34+ cell yield in the first PBSC collection after mobilization with 4 or 5 days of G-CSF treatment. Associations were recorded between these outcomes and donor factors (age, sex, weight, ethnicity), mobilization factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume [PBV]) or laboratory factors (blood cell counts at baseline or after mobilization). The 52 studies evaluated between 15 and 20,884 donors. Forty-three studies were retrospective, 33 assessed blood CD34+ cell counts, and 39 assessed CD34+ cell yield from PBSCs. Blood CD34+ cell counts consistently predicted CD34+ cell yield. Younger donors usually had higher blood CD34+ cell counts and CD34+ cell yield. Most studies that investigated the effect of donor ancestry found that donors of non-European ancestry had higher blood CD34+ cell counts after mobilization and higher CD34+ cell yields from collection. The poor consensus about the best predictors of blood CD34+ cell count and yield necessitates further prospective studies, particularly of the role of donor ancestry. The current focus on donor sex as a major predictor requires re-evaluation.

Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health.

Mitochondrial supercomplexes form around a conserved core of monomeric complex I and dimeric complex III; wherein a subunit of the former, NDUFA11, is conspicuously situated at the interface. We identified nduf-11 (B0491.5) as encoding the Caenorhabditis elegans homologue of NDUFA11. Animals homozygous for a CRISPR-Cas9-generated knockout allele of nduf-11 arrested at the second larval (L2) development stage. Reducing (but not eliminating) expression using RNAi allowed development to adulthood, enabling characterisation of the consequences: destabilisation of complex I and its supercomplexes and perturbation of respiratory function. The loss of NADH dehydrogenase activity was compensated by enhanced complex II activity, with the potential for detrimental reactive oxygen species (ROS) production. Cryo-electron tomography highlighted aberrant morphology of cristae and widening of both cristae junctions and the intermembrane space. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development presumably arises due to its involvement in complex I and supercomplex maintenance. This highlights the importance of respiratory complex integrity for health and the potential for its perturbation to cause mitochondrial disease. This article has an associated First Person interview with Amber Knapp-Wilson, joint first author of the paper.