US20230235289 METHOD FOR FIBROBLAST REJUVENATION BY MECHANICAL REPROGRAMMING AND REDIFFERENTIATION

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United States of America

Application Number 17918981

Application Date 30.03.2021

Publication Number 20230235289

Publication Date 27.07.2023

Publication Kind A1

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Applicants Paul Scherrer Institut

Inventors G.V. Shivashankar
Bibhas Roy

Priority Data 20169459.3 14.04.2020 EP

Title

(EN) METHOD FOR FIBROBLAST REJUVENATION BY MECHANICAL REPROGRAMMING AND REDIFFERENTIATION

Abstract

(EN)

Over the course of an aging process fibroblasts lose contractility, leading to reduced connective tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacements with a laterally confined growth of fibroblasts on micro-patterned substrates that induces stem cell-like spheroids. The partially reprogrammed spheroids are embedded in collagen-I matrices of varying densities, mimicking different 3D tissue constraints. The spheroids regain their fibroblastic properties and sprout to form 3D connective tissue networks. The differentiated fibroblasts exhibit reduced DNA damage, enhanced cytoskeletal gene expression and acto-myosin contractility. The rejuvenated fibroblasts show increased matrix protein (fibronectin and laminin) deposition and collagen remodeling compared to the parental fibroblast tissue network. The partially reprogrammed cells have comparatively open chromatin compaction states and may be more poised to redifferentiation into contractile fibroblasts in 3D-collagen matrix. Collectively, the results highlight efficient fibroblast rejuvenation, with important implications in regenerative medicine.

C	CHEMISTRY; METALLURGY
12	BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N	MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5	Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07	Animal cells or tissues
071	Vertebrate cells or tissues, e.g. human cells or tissues
077	Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells

C	CHEMISTRY; METALLURGY
12	BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N	MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5	Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07	Animal cells or tissues
071	Vertebrate cells or tissues, e.g. human cells or tissues
077	Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells

C	CHEMISTRY; METALLURGY
12	BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N	MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2506	Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
13	from connective tissue cells, from mesenchymal cells
1307	from adult fibroblasts

C	CHEMISTRY; METALLURGY
12	BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N	MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5	Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor;
06	Animal cells or tissues; Human cells or tissues
0602	Vertebrate cells
0652	Cells of skeletal and connective tissues; Mesenchyme
0656	Adult fibroblasts

C	CHEMISTRY; METALLURGY
12	BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N	MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2527	Culture process characterised by the use of mechanical forces, e.g. strain, vibration

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