In a landmark study set to reshape our understanding of aging and regenerative biology, scientists have unveiled compelling evidence that factors circulating in young human blood serum can elicit rejuvenating effects on human skin cells—but crucially, this effect depends on the presence and mediation of bone marrow-derived cells. Published in the July 2025 issue of Aging (Aging-US), this research illuminates an intricate cellular dialogue between skin and bone marrow, revealing a previously underappreciated axis through which systemic factors influence tissue regeneration and potentially combat age-related decline.
The study, led by researchers Johanna Ritter and Elke Grönniger at Beiersdorf AG’s Research and Development center in Hamburg, employs a sophisticated microphysiological co-culture system designed to simulate human tissue environments with remarkable fidelity. This system connects a three-dimensional (3D) skin equivalent with a 3D bone marrow (BM) model under dynamic conditions intended to mimic in vivo circulation. By introducing human serum samples from young and old donors into these co-cultures, the team dissected how age-associated systemic factors modulate skin biology through interactions with the bone marrow niche.
One of the most striking findings was that young human serum, when applied alone to skin models, failed to produce significant rejuvenation. However, when skin was co-cultured alongside bone marrow cells, aged skin models exhibited markedly enhanced regenerative markers in the presence of young serum. This was evidenced by a significant increase in Ki67-positive cells, a hallmark indicating heightened proliferative activity and tissue regeneration. The result underscores the pivotal role of bone marrow as a cellular intermediary, translating systemic rejuvenation cues into functional effects on distal organs such as the skin.
To delve deeper mechanistically, the researchers used tandem liquid chromatography-ion mobility spectrometry-mass spectrometry (LC-IMS-MS/MS) proteomics to catalog proteins secreted by bone marrow cells exposed to either young or old human serum over a five-week culture period. This high-resolution proteomic analysis identified 55 proteins whose abundance was significantly modulated by the youthful serum environment. Among these proteins, seven were linked to key biological processes including cell renewal, extracellular matrix synthesis, and mitochondrial energy metabolism—processes intimately tied to cellular youthfulness and tissue homeostasis.
This proteomic signature not only revealed a repertoire of secreted factors potentially responsible for skin rejuvenation but also offered insight into the cellular origins of these molecules within the bone marrow compartment. By integrating protein expression data from distinct bone marrow cell populations—such as granulocytes, progenitor cells, and monocytes—the study mapped these secreted factors’ cellular sources. This cellular mapping suggests that specific bone marrow subsets act as critical responders to systemic signals, orchestrating downstream regenerative effects in peripheral tissues.
The findings provide a crucial mechanistic underpinning to longstanding observations from heterochronic parabiosis experiments in rodents—studies in which the circulatory systems of young and old animals are surgically joined, resulting in rejuvenation of aged tissues. While those experiments demonstrated remarkable cross-tissue rejuvenation, the molecular and cellular conduits remained elusive. This new human cell-based model clarifies that bone marrow cells serve as vital intermediaries, capable of sensing young systemic factors and secreting bioactive proteins that promote tissue renewal, particularly in the skin.
Beyond the basic science implications, the research carries significant translational potential. It identifies a panel of secreted proteins that could serve as therapeutic targets or biomarkers for developing interventions to mitigate skin aging. By harnessing the crosstalk between bone marrow and skin cells, future therapies might leverage these molecular mediators to restore youthful skin characteristics, including enhanced collagen production, increased cellular proliferation, and improved mitochondrial function.
Importantly, the research emphasizes that the systemic milieu alone—represented by young serum—is insufficient to drive skin rejuvenation without bone marrow participation. This highlights the necessity of multicellular, organ-level interactions in mediating complex biological phenomena like aging. The in vitro co-culture approach adopted in the study sets a new standard for investigating human tissue communication and could be extended to other organ systems where bone marrow- or blood-derived cells modulate tissue regeneration.
The authors are cautious to note that these findings are currently preclinical and derived from in vitro human tissue models. Although highly informative, translating these results into viable human therapies will require extensive further research, including rigorous validation in clinical contexts. Safety, delivery mechanisms, and sustained efficacy over time remain critical hurdles to address before the promise of systemic factor-driven rejuvenation can be realized.
Nonetheless, this study provides a sophisticated proof-of-concept that systemic factors from young individuals wield rejuvenating potential on skin via bone marrow mediation. It sparks a paradigm shift—moving away from direct application of young blood factors towards recognizing the indispensable role of bone marrow-derived cellular networks in translating systemic cues into targeted tissue renewal.
With aging populations worldwide facing increasing skin-related morbidities and cosmetic concerns, such foundational insights into the interplay of systemic biology and tissue-specific responses mark an exciting frontier. They offer hope for innovative treatments that may preserve skin integrity, improve wound healing, and potentially delay or reverse visible signs of aging in the near future.
In sum, this research represents a significant advancement in the quest to decode aging’s biological complexity. By integrating human serum proteomics, microphysiological modeling, and cellular biology, the study provides a nuanced understanding of how youthful systemic factors can contact and activate bone marrow cells to secrete regenerative mediators essential for skin rejuvenation. It opens new avenues for regenerative medicine and highlights the indispensable role of bone marrow in maintaining skin health and combating aging.
The full paper, titled “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,” was published on July 25, 2025, and is available via DOI: 10.18632/aging.206288. Correspondence regarding the study can be directed to Elke Grönniger at Beiersdorf AG.
Subject of Research: Cells
Article Title: 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
News Publication Date: July 25, 2025
Image Credits: 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).
Keywords: aging, skin rejuvenation, microphysiological systems, systemic factors, bone marrow model, human serum
