Research Paper Advance Articles
Systemic factors in young human serum influence in vitro responses of human skin and bone marrow-derived blood cells in a microphysiological co-culture system
- 1 Beiersdorf AG, Research and Development, Hamburg, Germany
- 2 Institute for Bioanalytics, Coburg University of Applied Sciences and Arts, Coburg, Germany
- 3 Proteomics Unit, Department Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
- 4 Zoological Institute, Kiel University, Kiel, Germany
Received: February 25, 2025 Accepted: June 20, 2025 Published: July 25, 2025
https://doi.org/10.18632/aging.206288How to Cite
Copyright: © 2025 Ritter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Aging is a complex process that significantly contributes to age-related diseases and poses significant challenges for effective interventions, with few holistic anti-aging approaches successfully reversing its signs. Heterochronic parabiosis studies illuminated the potential for rejuvenation through blood-borne factors, yet the specific drivers including underlying mechanisms remain largely unknown and until today insights have not been successfully translated to humans. In this study, we were able to recreate rejuvenation of the human skin via systemic factors using a microphysiological system including a 3D skin model and a 3D bone marrow model. Addition of young human serum in comparison to aged human serum resulted in an improvement of proliferation and a reduction of the biological age as measured by methylation-based age clocks in the skin tissue. Interestingly, this effect was only visible in the presence of bone marrow-derived cells. Further investigation of the bone marrow model revealed changes in the cell population in response to young versus aged human serum treatment. Using proteome analysis, we identified 55 potential systemic rejuvenating proteins produced by bone marrow-derived cells. For seven of these proteins, we were able to verify a rejuvenating effect on human skin cells using hallmarks of aging assays, supporting their role as systemic factors rejuvenating human skin tissue.
Abbreviations
BM: bone marrow; CD55: complement decay-accelerating factor; CHI3L1: chitinase-3-like 1 protein; CLPs: common lymphoid progenitor cells; CMPs: common myeloid progenitor cells; Col IV: collagen IV; CST7: cystatin F; FCAR Fc: fragment of IgA receptor; FCS: fetal calf serum; FLT3-L: Fms-related tyrosine kinase 3 ligand; GDF-11: growth differentiation factor; GM-CSF: granulocyte-monocyte-colony stimulating factor; GMPs: granulocyte-monocyte progenitor cells; HSCs: hematopoietic stem cells; Kr10: keratin 10; Kr14: keratin 14; M-CSF: macrophage-colony stimulating factor; MEPs: megakaryocyte-erythroid progenitor cells; MMP: matrix-metalloproteinase; MPPs: multipotent progenitors; MPS: microphysiological system; MSCs: mesenchymal stem cells; P/S: penicillin-streptomycin; SCF: stem cell factor; SEM: standard errors of the mean; SPINT1: kunitz-type protease inhibitor 1; THBS4: thrombospondin-4; TIMP-2: tissue inhibitor of metalloproteinases 2; TPO: thrombopoietin.