TY  - JOUR
AB  - Distal injuries in human fingertips can regenerate almost fully, yet the process of human fingertip regeneration has hardly been characterized on a cellular and molecular level. A silicone finger cap, comprising a puncturable reservoir, was used to treat 22 human fingertip amputations. In all patients, subcutaneous tissue, nailbed and skin regenerated with excellent outcomes. Through the clinical assessment of the wounds, the regenerative process was divided into four distinct phases. Proteomic data from wound fluid samples collected at regular intervals, confirmed robust and unbiasedly distinct proteomic signatures, characteristic processes, and active regulatory networks in each phase. Moreover, this human dataset provides important insights, showing clear divergences from findings in regenerative animal models. The longitudinal and comprehensive analysis presented here unveils the complex orchestration of four clinically and proteomically-distinct phases of human fingertip regeneration. Further analyses of this proteomic data will allow for the identification of candidates orchestrating human fingertip regeneration and serving as a framework for comparative and regenerative medicine studies. This clinical trial was registered at ClinicalTrials.gov Identifier: NCT03089060 on March 17, 2017.
AU  - Schultz, J.*
AU  - Patel, P.A.*
AU  - Aires, R.*
AU  - Wissing, L.*
AU  - Glatte, P.*
AU  - Seifert, M.*
AU  - Gentzel, M.*
AU  - Fitze, G.*
AU  - Doyle, A.M.*
AU  - Sandoval-Guzmán, T.
C1  - 75963
C2  - 58283
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
TI  - Human fingertip regeneration follows clinical phases with distinct proteomic signatures.
JO  - npj Reg. Med.
VL  - 10
IS  - 1
PB  - Nature Portfolio
PY  - 2025
SN  - 2057-3995
ER  - 

TY  - JOUR
AB  - There is an urgent need for innovative therapies targeting defective epithelial repair in chronic diseases like COPD. The mesenchymal niche is a critical regulator in epithelial stem cell activation, suggesting that their secreted factors are possible potent drug targets. Utilizing a proteomics-guided drug discovery strategy, we explored the lung fibroblast secretome to uncover impactful drug targets. Our lung organoid assays identified several regenerative ligands, with osteoglycin (OGN) showing the most profound effects. Transcriptomic analyses revealed that OGN enhances alveolar progenitor differentiation, detoxifies reactive oxygen species, and strengthens fibroblast-epithelial crosstalk. OGN expression was diminished in COPD patients and smoke-exposed mice. An active fragment of OGN (leucine-rich repeat regions 4-7) replicated full-length OGN's regenerative effects, significantly ameliorating elastase-induced lung injury in lung slices and improving lung function in vivo. These findings highlight OGN as a pivotal secreted protein for alveolar epithelial repair, positioning its active fragment as a promising therapeutic for COPD.
AU  - van der Koog, L.*
AU  - Woest, M.E.*
AU  - Gorter, I.C.*
AU  - Verschut, V.*
AU  - Elferink, R.A.B.*
AU  - Zuidhof, A.B.*
AU  - Nugraha, D.F.*
AU  - Koloko Ngassie, M.L.*
AU  - Bos, S.I.T.*
AU  - Dhakad, D.
AU  - Wolters, J.C.*
AU  - Horvatovich, P.L.*
AU  - Prakash, Y.S.*
AU  - Timens, W.*
AU  - Yildirim, A.Ö.
AU  - Brandsma, C.A.*
AU  - Frijlink, H.W.*
AU  - Nagelkerke, A.*
AU  - Gosens, R.*
C1  - 73790
C2  - 57225
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
TI  - Fibroblast-derived osteoglycin promotes epithelial cell repair.
JO  - npj Reg. Med.
VL  - 10
IS  - 1
PB  - Nature Portfolio
PY  - 2025
SN  - 2057-3995
ER  - 

TY  - JOUR
AB  - In regenerating tissues, synthesis and remodeling of membranes rely on lipid turnover and transport. Our study addresses lipid adaptations in intestinal regeneration of Drosophila melanogaster and limb regeneration of Ambystoma mexicanum. We found changes in lipid profiles at different locations: transport, storage organs and regenerating tissues. We demonstrate that attenuating insulin signaling, exclusively in fat storage, inhibits the regeneration-specific response in both the fat storage and the regenerating tissue in Drosophila. Furthermore, in uninjured axolotls we found sex-specific lipid profiles in both storage and circulation, while in regenerating animals these differences subside. The regenerating limb presents a unique sterol profile, albeit with no sex differences. We postulate that regeneration triggers a systemic response, where organs storing lipids play a significant role in the regulation of systemic lipid traffic. Second, that this response may be an active and well-regulated mechanism, as observed when homeostatic sex-differences disappear in regenerating salamanders.
AU  - Kübler, I.C.*
AU  - Kretzschmar, J.*
AU  - Arredondo-Lasso, M.N.*
AU  - Keeley, S.D.*
AU  - Rößler, L.C.*
AU  - Ganß, K.
AU  - Sandoval-Guzmán, T.
AU  - Brankatschk, M.*
C1  - 72196
C2  - 56478
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
TI  - Systemic and local lipid adaptations underlie regeneration in Drosophila melanogaster and Ambystoma mexicanum.
JO  - npj Reg. Med.
VL  - 9
IS  - 1
PB  - Nature Portfolio
PY  - 2024
SN  - 2057-3995
ER  -