Evidence map›Paper›PMID 39551765›Full record

ArticleStem cell research & therapy2024

Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium.

Darja Marolt Presen, Vanessa Goeschl, Dominik Hanetseder, Laura Ogrin, Alexandra-Larissa Stetco, Anja Tansek, Laura Pozenel, Bella Bruszel, Goran Mitulovic, Johannes Oesterreicher and 5 more

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Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Darja Marolt PresenLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria. darja.marolt.presen@ki.si.ORCID 0000-0003-3638-4619
Vanessa GoeschlLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Dominik HanetsederLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Laura OgrinLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Alexandra-Larissa StetcoLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Anja TansekLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Laura PozenelLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Bella BruszelInstitute of Science and Technology Austria, Am Campus 1, Klosterneuburg, 3400, Austria.
Goran MitulovicClinical Department of Laboratory Medicine Proteomics Core Facility, Medical University of Vienna, Spitalgasse 23, Vienna, 1090, Austria.
Johannes OesterreicherLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Johannes ZipperleLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Barbara SchaedlLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Wolfgang HolnthonerLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Johannes GrillariLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.
Heinz RedlLudwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Donaueschingenstrasse 13, Vienna, A-1200, Austria.

Funding

FFG Austria FEMtech Praktika 852154FFG Austria FEMtech Praktika 868917, 877951FFG Austria Industrienahe Dissertation 853056FFG Austria Industrienahe Dissertation 867803FFG Austria Production of the Future 877452H2020 Marie Skłodowska-Curie Actions 657716Horizon 2020 Framework Programme 953134
6 · The paper itself

Abstract

backgroundHuman induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM.

methodsMSCs were isolated from 13 donors (age 20-90 years). CM derived from hiPSC-MPs was added to the MSC cultures and the effects on proliferation and osteogenic differentiation were examined after 14 days and 6 weeks. The stimulatory activity of hiPSC-MP-CM was compared with the activity of MSC-derived CM and with the activity of CM prepared from hiPSC-MPs pre-cultured in growth or osteogenic medium for 14 days. Comparative proteomic analysis of CM was performed to gain insight into the molecular components responsible for the stimulatory activity.

resultsPrimary bone marrow-derived MSC exhibited variability, with a tendency towards lower proliferation and tri-lineage differentiation in older donors. hiPSC-MP-CM increased the proliferation and alkaline phosphatase activity of MSC from several adult/aged donors after 14 days of continuous supplementation under osteogenic conditions. However, CM supplementation failed to improve the mineralization of MSC pellets after 6 weeks under osteogenic conditions. hiPSC-MP-CM showed greater enhancement of proliferation and ALP activity than CM derived from bone marrow-derived MSCs. Moreover, 14-day cultivation but not osteogenic pre-differentiation of hiPSC-MPs strongly enhanced CM stimulatory activity. Quantitative proteomic analysis of d14-CM revealed a distinct profile of components that formed a highly interconnected associations network with two clusters, one functionally associated with binding and organization of actin/cytoskeletal components and the other with structural constituents of the extracellular matrix, collagen, and growth factor binding. Several hub proteins were identified that were reported to have functions in cell-extracellular matrix interaction, osteogenic differentiation and development.

conclusionsOur data show that hiPSC-MP-CM enhances early osteogenic differentiation of human bone marrow-derived MSCs and that prolonged cultivation of hiPSC-MPs enhances CM-stimulatory activity. Proteomic analysis of the upregulated protein components provides the basis for further optimization of hiPSC-MP-CM for bone regenerative therapies.

Indexed as

Cell DifferentiationCell ProliferationInduced Pluripotent Stem CellsMesenchymal Stem CellsOsteogenesisAdultAgedAged, 80 and overCells, CulturedCulture Media, ConditionedFemaleHumansMaleMiddle AgedProteomicsYoung AdultCulture Media, ConditionedAgingConditioned mediumHuman bone marrow mesenchymal stromal cellsHuman iPSCsMesenchymal progenitorsOsteogenic differentiationProteomic analysisSecretome

Identifiers

PMID39551765
PMCPMC11572509

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.