Lucija Kadunc (Author), Duško Lainšček (Author), Rok Gašperšič (Author), Petra Sušjan (Author), Uroš Kovačič (Author), Miha Butinar (Author), Boris Turk (Author), Roman Jerala (Author), Iva Hafner Bratkovič (Author)

Abstract

Growth factors are the key regulators that promote tissue regeneration and healing processes. While the effects of individual growth factors are well documented, a combination of multiple secreted growth factors underlies stem cell–mediated regeneration. To avoid the potential dangers and laborintensive individual approach of stem cell therapy while maintaining their regeneration-promoting effects based on multiple secreted growth factors, we engineered a “mix-and-match” combinatorial platform based on a library of cell lines producing growth factors. Treatment with a combination of growth factors secreted by engineered mammalian cells was more efficient than with individual growth factors or even stem cell–conditioned medium in a gap closure assay. Furthermore, we implemented in a mouse model a device for allogenic cell therapy for an in situ production of growth factors, where it improved cutaneous wound healing. Augmented bone regeneration was achieved on calvarial bone defects in rats treated with a cell device secreting IGF, FGF, PDGF, TGF-β, and VEGF. In both in vivo models, the systemic concentration of secreted factors was negligible, demonstrating the local effect of the regeneration device. Finally, we introduced a genetic switch that enables temporal control over combinations of trophic factors released at different stages of regeneration mimicking the maturation of natural wound healing to improve therapy and prevent scar formation.

Keywords

celjenje ran;regeneracija kosti;rastni faktorji;wound healing;bone regeneration;growth factors;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: KI - National Institute of Chemistry
Publisher: Frontiers Editorial Office
UDC: 61
COBISS: 152044035 Link will open in a new window
ISSN: 2296-4185
Views: 39
Downloads: 5
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Other data

Secondary language: Slovenian
Secondary keywords: celjenje ran;regeneracija kosti;rastni faktorji;
Type (COBISS): Article
Source comment: Soavtorji: Duško Lainšček, Rok Gašperšič, Petra Sušjan-Leite, Uroš Kovačič, Miha Butinar, Boris Turk, Roman Jerala and Iva Hafner-Bratkovič; Nasl. z nasl. zaslona; Opis vira z dne 15. 5. 2023;
Pages: str. 1-16
Issue: ǂVol. ǂ11
Chronology: 2023
DOI: 10.3389/fbioe.2023.1168330
ID: 23187643