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Biomimetic strategy for cartilage formation: synergy of stem cell micro-aggregates and supramolecular peptide nanofibers

ABSTRACT: Biomimetic strategy for cartilage formation: synergy of stem cell micro-aggregates and supramolecular peptide nanofibers

PROVIDER: PRJNA552994 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9649590.fastq.gz	Fastqsanger.gz
	SRR9649600.fastq.gz	Fastqsanger.gz
	SRR9649591.fastq.gz	Fastqsanger.gz
	SRR9649601.fastq.gz	Fastqsanger.gz
	SRR9649592.fastq.gz	Fastqsanger.gz

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Biomimetic strategy for cartilage formation: synergy of stem cell micro-aggregates and supramolecular peptide nanofibers

Project description:Recapitulation of embryonic developmental events is receiving increasing recognition as a strategy to induce robust tissue regeneration. In this work, we aimed to explore the critical events of cartilage formation by combining adult human bone marrow-derived mesenchymal stromal cells (hBMSCs) with supramolecular nanofibrous hydrogel. The micro-aggregation led to the altered global transcriptional profiles of hBMSCs and enhanced chondrogenic commitment early in 24h. Furthermore, the supramolecular nanofiber structure formed by peptide amphiphiles (PAs) maintained the cell cohesion and favored the deposition of cartilaginous matrix, thus facilitating the progression of differentiation. Upon subcutaneous implantation, the hBMSCs microaggregates-laden PA hydrogel demonstrated evident ectopic cartilage formation. Notably, RNA-sequencing data illustrated that the PA hydrogel facilitated the in vivo chondrogenesis progression of the encapsulated donor cells, and also activated the chondrogenesis in the host tissue via paracrine signaling. We conclude that PA hydrogel delivering microaggregates of hBMSCs could recapitulate the critical developmental events during cartilage development. This bioinspired approach will offer the potential to regenerate functional and durable tissues for the functional recovery of traumatic injuries of the cartilaginous skeleton .

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Project description:One of strategies to regenerate cartilage defect is transplantation of mesenchymal stem cells (MSCs). Improvements of therapeutic potential of MSCs are needed to achieve successful cartilage regeneration by transplantation of a limited number of cells. Aggregated culture is a popular method in ES and iPS cells to maintain or enhance their potentials. Here we investigated gene expression profile of aggregated MSCs. 621 genes were up-regulated and 409 genes were down-regulated more than 5-fold in MSC-aggregates compared with the number in MSCs in a monolayer culture. The most up-regulated gene was BMP2, which is one of the genes involved in chondrogenesis. Anti-inflammatory genes were also up-regulated in MSC-aggregates. The microarray data for selected genes were confirmed by real-time PCR. Human synovial MSCs was isolated from synovium of 3 distinct donors. The gene expression profile of MSC-aggregates cultured in hanging drop for 3days was compared with that of MSCs in a monolayer culture.

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