Hematopoietic stem cells (HSCs) are rare cells residing in the bone marrow and give rise to millions of new blood cells daily throughout life. Because of their multipotent, self-renewing nature, they have also been used for several decades to treat hematological disorders. However, HSCs are scarce and difficult to maintain ex vivo, demonstrating the need for developing novel in vitro methods to expand HSCs that mimic the complex in vivo microenvironment in suitable culture tissue plates, in extracellular matrix scaffolds, or on a biochip. One component to include in such an artificial microenvironment is HSC-related growth factors (GFs) immobilized on surfaces that mimic membrane-bound GFs in vivo. In this paper, we have initiated the development of an ex vivo system to study the immobilization of growth factors that sustain HSC maintenance and possibly expansion. However, since HSC-related GFs are expensive we have developed a proof-of-concept model using bovine serum albumin (BSA) as an alternative. Polypyrrole (PPy) was electrochemically synthesized in the presence of dicarboxylic acids with different hydrocarbon chain lengths and polycarboxylic acids with different molecular weights as dopants. BSA was immobilized on the PPy surface using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to couple BSA to the carboxylic acid dopant of PPy. These PPy films with different dopants showed different abilities to immobilize BSA using EDC/NHS coupling and also different surface properties. In addition, owing to the interesting switchable properties of PPy upon alteration of the oxidation/reduction potential, the immobilized BSA could change its presentation on the PPy surface depending on the redox state. To characterize the PPy surfaces and to study the different immobilization results of BSA on these PPy variants with different dopants and different presentation behavior upon redox switching, the electrochemical properties, hydrophobicity, thickness, roughness, surface COOH density and fluorescence labeling were investigated. The results indicate that the polycarboxylic acid dopants could immobilize more BSA on the PPy surface. Moreover, the BSA in the as-fabricated state shows a "collapsed" presentation on the PPy surface, a "less collapsed" presentation in the oxidized state and an "erected" presentation in the reduced state. Cell viability studies using hematopoietic cells showed that the developed PPy-BSA surfaces did not negatively alter cell viability or cell proliferation compared to the control.

LiRE25 is a comprehensive evaluation of research at LiU. The core of the evaluation is the quality of research, but it also addresses research culture and the conditions for research. The purpose is to provide a basis for future quality work. The focus of LiRE25 is the evaluation units, which in most cases correspond to divisions at LiU’s twelve departments, and where Malmstens at Campus Lidingö also constituts an evaluation unit. 

LiRE25 is commissioned by the Vice-Chancellor. The design of the evaluation method and the planning and implementation of the evaluation have mainly been handled as a project in which the project group, the LiRE25 office, has done most of the work, but where several other parts of LiU’s organisation have also participated. 

The evaluation was carried out in two stages, a self-evaluation that each evaluation unit carried out in the autumn of 2024 followed by an external expert review in the spring of 2025. The external review was carried out by panels and resulted in recommendations aimed at both the evaluation units and other parts of LiU’s organisation. This final report is based on the self-evaluations and the panels’ re­ports. 

The self-evaluations have been the most important basis for the external review, but they have also had the dual purpose of providing the divisions with inspiration for how future quality work can be conducted. In addition, it has given LiU’s researchers the opportunity to express their views on how the university as a whole can be developed. As a side effect, the self-evaluations also contain many examples of successful quality work that other divisions can be inspired by. 

The panel reports contain recommendations that, for example, highlight the need for an expanded strategic thinking regarding future research directions, recruitments and scientific publication. Several of the panels have also identified the care of young researchers as an area that can be developed, as well as the mo­bility of LiU’s researchers. Increased international engagement is also highlighted as important by the panels. This applies to research collaborations as well as co-publication and to making better use of opportunities for EU funding. At the university level, the panels raise issues concerning LiU’s organisation and how the LiU strategy work can have a greater impact at the department and division level. 

This final report aims to provide an overview of the results of the evaluation. It can be read by all LiU employees, and particularly those who are in some way involved in research or research-supporting activities. The panels’ reports are also published on LiU’s website, and it will also be possible to interact with these texts via a chatbot. However, further work on using the results of LiRE25 at division level should primarily be based on the panels’ specific recommendations to each evaluation unit and the evaluation unit’s own self-evaluation. 

The Vice-Chancellor’s decision (Dnr LiU-2023-04517) to implement LiRE25 states: The research evaluation is an important part of the work on research quali­ty, but also in LiU’s strategy work. As part of Vision 2030 within the target area of Excellence and Benefit, the research evaluation is an important piece of the puzzle in how LiU can strategically develop its research going forward. It is a statement that signals that the results of LiRE25 will be used both for immediate efforts and for long-term strategic work. It is a strong hope that this report, together with oth­er documentation produced by the evaluation, will not only inspire quality work but also lead to an actual quality increase in the research at LiU! 

LiRE25 är en heltäckande utvärdering av forskning vid LiU. Utvärderingens kärna är forskningens kvalitet, men den tar också upp forskningskultur och forskningens förutsättningar. Syftet är att ge underlag för framtida kvalitetsarbete. I fokus för LiRE25 finns de utvärderade enheterna, som i de flesta fall överensstämmer med avdelningar vid LiU:s tolv institutioner och där också Malmstens vid Campus Lidingö utgjorde en utvärderad enhet.

LiRE25 är beställd av rektor. Utformningen av utvärderingsmetod samt planering och genomförande av utvärderingen har i huvudsak hanterats som ett projekt där projektgruppen, LiRE25-kansliet, gjort det mesta av arbetet men där också flera andra delar av LiU:s organisation medverkat.

Utvärderingen genomfördes i två steg, en självvärdering som varje utvärderad enhet genomförde under hösten 2024 följt av en extern expertgranskning under våren 2025. Expertgranskningen genomfördes av paneler och resulterade i rekommendationer riktade till såväl de utvärderade enheterna som till andra delar av LiU:s organisation. Denna slutrapport baseras på självvärderingarna samt panelernas rapporter.

Självvärderingarna har varit det viktigaste underlaget för expertgranskningen men de har också haft det dubbla syftet att ge avdelningarna inspiration till hur framtida kvalitetsarbete kan bedrivas. Dessutom, har det gett LiU:s forskare möjligheten att framföra synpunkter på hur universitetet i sin helhet kan utvecklas. Lite som en sidoeffekt finns i självvärderingarna också många exempel på framgångsrikt kvalitetsarbete som andra avdelningar kan inspireras av.

Panelrapporterna innehåller rekommendationer som till exempel lyfter behovet av ett utökat strategiskt tänk kring framtida forskningsinriktningar, rekry­teringar och vetenskaplig publicering. Flera av panelerna har också identifierat omhändertagandet av unga forskare som ett område som kan utvecklas liksom mobiliteten bland LiU:s forskare. Även ett utökat internationellt engagemang framhålls som viktigt av panelerna. Det gäller såväl forskningssamarbeten som sampublicering och att bättre utnyttja möjligheter till EU-finansiering. På det universitetsövergripande planet lyfter panelerna frågor kring LiU:s organisation samt hur det LiU-gemensamma strategiarbetet kan få större påverkan ut på av­delningsnivå.

Denna slutrapport syftar till att ge en översiktlig bild av utvärderingens resultat. Den kan med fördel läsas av alla LiU-medarbetare men särskilt de som på något sätt är inblandade i forskning eller forskningsstödjande verksamhet. Panelernas rapporter finns också publicerade på LiU:s webbplats och det kommer även att vara möjligt att interagera med dessa texter via en chattbot. Det fortsatta arbetet med att använda resultaten från LiRE25 på avdelningsnivå bör dock främst utgå från panelernas enhetsspecifika rekommendationer och den utvärderade enhetens egen självvärdering.

I rektors beslut (Dnr LiU-2023-04517) att genomföra LiRE25 står: Forskningsutvärderingen är en viktig del i arbetet med forskningskvalitet men också inom LiU:s strategiarbete. Som en del av Vision 2030 inom målområdet Excellens och nytta är forskningsutvärderingen en viktig pusselbit i hur LiU strategiskt kan utveckla sin forskning framåt. Det är en formulering som signalerar att resultatet av LiRE25 ska användas både för omedelbara insatser och för ett långsiktigt stra­tegiskt arbete. Det är en stark förhoppning från alla inblandade i LiRE25 att den­na rapport tillsammans med annat underlag som utvärderingen producerat inte bara inspirerar kvalitetsarbetet utan också leder till en faktisk kvalitetshöjning av forskningen vid LiU!

Aims: Adaptation to low oxygen of hematopoietic stem cells (HSCs) in the bone marrow has been demonstrated to depend on the activation of hypoxia-inducible factor (HIF)-1α as well as the limited production of reactive oxygen species (ROS). In this study, we aimed at determining whether HIF-1α is involved in protecting HSCs from ROS.

Results: Oxidative stress was induced by DL-buthionine-(S,R)-sulfoximine (BSO)-treatment, which increases the mitochondrial ROS level. Hypoxia rescued Lineage-Sca-1⁺c-kit⁺ (LSK) cells from BSO-induced apoptosis, whereas cells succumbed to apoptosis in normoxia. Apoptosis in normoxia was inhibited with the antioxidant N-acetyl-L-cysteine or by overexpression of anti-apoptotic BCL-2. Moreover, stabilized expression of oxygen-insensitive HIFs could not protect LSK cells from oxidative stress-induced apoptosis at normoxia, neither could short hairpin RNA to Hif-1α inhibit the protective effects by hypoxia in LSK cells. Likewise, BSO treatment of LSK cells from Hif-1α knockout mice did not suppress the effects seen in hypoxia. Microarray analysis identified the nuclear factor-kappa B (NF-κB) pathway as a pathway induced by hypoxia. By using NF-κB lentiviral construct and DNA-binding assay, we found increased NF-κB activity in cells cultured in hypoxia compared with normoxia. Using an inhibitor against NF-κB activation, we could confirm the involvement of NF-κB signaling as BSO-mediated cell death was significantly increased in hypoxia after adding the inhibitor.

Innovation: HIF-1α is not involved in protecting HSCs and progenitors to elevated levels of ROS on glutathione depletion during hypoxic conditions.

Conclusion: The study proposes a putative role of NF-κB signaling as a hypoxia-induced regulator in early hematopoietic cells.

The phosphatidylinositol 3-kinase/AKT pathway is an integral component of signaling involved in the development of many cancers, including myeloid leukemias such as chronic myeloid leukemia and acute myeloid leukemia (AML). Increased AKT1 activity is frequently seen in AML patients, providing leukemic cells with growth and survival promoting signals. An important aspect of AKT1 function is its involvement in cellular metabolism and energy production. Under some circumstances, strong activation of AKT1 increases oxidative stress, which can cause apoptosis when cells progressively build up excess free radicals. This has been described in hematopoietic cells overexpressing activated AKT1; however, whether this is true in cells coexpressing other genetic events involved in leukemia is not known. This prompted us to investigate the effect of constitutively active AKT1 (myristoylated AKT1) in hematopoietic progenitor cells expressing constitutively active signal transducer and activator of transcription 5, Fms-related tyrosine kinase 3-internal tandem duplication, or antiapoptotic B-cell lymphoma 2. Surprisingly, myristoylated AKT1 was incompatible with proliferation driven by both signal transducer and activator of transcription 5 and Fms-related tyrosine kinase 3-internal tandem duplication, which triggered cell cycle block and apoptosis. Moreover, transplantable cells of B-cell lymphoma 2-transgenic mice were impaired in their engraftment ability to recipient mice when expressing hyperactivated AKT1. This Was linked to AKT1-mediated proapoptotic functions and not to impairment in homing to the bone marrow. Although cells expressing hyperactivated AKT1 displayed higher levels of reactive oxygen species both in vitro and in vivo, the addition of the antioxidant N-acetyl-L-cysteine significantly reduced apoptosis. Taken together, the results indicate that constitutive AKT1 activity is incompatible with growth- and survival-promoting ability of other activated genes in AML. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.