Human Bone-Marrow-Derived Stem-Cell-Seeded 3D Chitosan–Gelatin–Genipin Scaffolds Show Enhanced Extracellular Matrix Mineralization When Cultured under a Perfusion Flow in Osteogenic Medium DOI Open Access
Gabriele Boretti, Emanuele� Giordano, Mariana Ioniţă

et al.

Materials, Journal Year: 2023, Volume and Issue: 16(17), P. 5898 - 5898

Published: Aug. 29, 2023

Tissue-engineered bone tissue grafts are a promising alternative to the more conventional use of natural donor grafts. However, choosing an appropriate biomaterial/scaffold sustain cell survival, proliferation, and differentiation in 3D environment remains one most critical issues this domain. Recently, chitosan/gelatin/genipin (CGG) hybrid scaffolds have been proven as suitable induce osteogenic commitment undifferentiated cells when doped with graphene oxide (GO). Some concern is, however, raised towards graphene-related material medical applications. The purpose work was thus check if potential CGG without added GO could be increased by improving medium diffusion culture differentiating cells. To aim, level extracellular matrix (ECM) mineralization evaluated human bone-marrow-derived stem (hBMSC)-seeded upon under perfusion flow dedicated custom-made bioreactor system. One week after initiating dynamic culture, histological/histochemical evaluations were carried out analyze early culture. analyses show enhanced ECM perfused compared static counterpart. results investigation reveal new perspective on efficient clinical applications GO.

Language: Английский

Extracellular Vesicles Generated by Mesenchymal Stem Cells in Stirred Suspension Bioreactors Promote Angiogenesis in Human-Brain-Derived Endothelial Cells DOI Open Access
Jolene Phelps, David A. Hart, Alim P. Mitha

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5219 - 5219

Published: May 10, 2024

Interrupted blood flow in the brain due to ischemic injuries such as stroke or traumatic injury results irreversible damage, leading cognitive impairment associated with inflammation, disruption of blood-brain barrier (BBB), and cell death. Since BBB only allows entry a small class drugs, many drugs used treat ischemia other tissues have failed brain-related disorders. The administration mesenchymal stem (MSC)-derived extracellular vesicles (EVs) has shown promise improving functional recovery following cerebral by inducing vessel formation. To facilitate treatment approach, it is necessary develop bioprocesses that can produce therapeutically relevant MSC-EVs reproducible scalable manner. This study evaluated feasibility using stirred suspension bioreactors (SSBs) scale-up serum-free production pro-angiogenic under clinically physioxic conditions. It was found MSCs grown SSBs generated EVs stimulated angiogenesis microvascular endothelial cells, supporting use for application ischemia. These properties were impaired at higher confluency, outlining importance considering time harvest when developing manufacture EV populations.

Language: Английский

Citations

2

Generating suspension-adapted human mesenchymal stromal cells (S-hMSCs) for the scalable manufacture of extracellular vesicles DOI Creative Commons
Pedro Silva Couto,

Dale J. Stibbs,

Braulio Carrillo Sanchez

et al.

Cytotherapy, Journal Year: 2024, Volume and Issue: 26(12), P. 1532 - 1546

Published: July 3, 2024

Human mesenchymal stromal cells (hMSCs) are a naturally adherent cell type and one of the most studied cellular agents used in therapy over last 20 years. Their mechanism action has been primarily associated with paracrine signalling, which contributed to an increase number studies focused on hMSC-related extracellular vesicles (EVs). In this study, we demonstrate for first time that human telomerase reverse transcriptase (hTERT) immortalised hMSCs can be adapted suspension culture, eliminating need microcarriers or other matrixes support growth. This novel line, named (S-hMSCs), doubling approximately 55 hours, growth rate 0.423 d−1. Regarding its immunophenotype characteristics, S-hMSCs retained close 90% CD73 CD105 expression levels, CD90 receptor being downregulated during adaptation process. An RNA sequencing analysis showed upregulation transcripts coding CD44, CD46 CD47 compared levels AT-hMSCs hTERT-hMSCs. The line herein established was able generate EVs using chemically defined medium formulation these nanoparticles averaging 150 nm size displaying markers CD63, CD81, TSG101, while not expressing negative marker calnexin. body evidence, combined visual confirmation EV presence transmission electron microscopy, demonstrates EV-producing capabilities S-hMSCs. provides platform process development, drug discovery translational field.

Language: Английский

Citations

2

Tumor Necrosis Factor Alpha Preconditioned Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Enhance the Inhibition of Necroptosis of Acinar cells in Severe Acute Pancreatitis DOI

Wangcheng Xie,

Tingyi Luo, Zhilong Ma

et al.

Tissue Engineering Part A, Journal Year: 2023, Volume and Issue: 29(23-24), P. 607 - 619

Published: Aug. 11, 2023

Severe acute pancreatitis (SAP) is a common abdominal emergency with high mortality rate and lack of effective therapeutic options. Although mesenchymal stem cell (MSC) transplantation potential treatment for SAP, the mechanism remains unclear. It has been suggested that MSCs may act mainly through paracrine effects; therefore, we aimed to demonstrate efficacy extracellular vesicles (EVs) derived from human umbilical cord cells (UCMSCs) SAP. Na-taurocholate was used induce rat SAP model retrograde injection into biliopancreatic duct. After 72 h EVs transplantation, pancreatic pathological damage alleviated, along decrease in serum amylase activity pro-inflammatory cytokine levels. Interestingly, when UCMSCs were preconditioned 10 ng/mL tumor necrosis factor alpha (TNF-α) 48 h, obtained (named TNF-α-EVs) performed an enhanced efficacy. Furthermore, both animal cellular experiments showed TNF-α-EVs alleviated necroptosis acinar RIPK3/MLKL axis. In conclusion, our study demonstrated able enhance effect on by inhibiting compared normal EVs. This heralds be promising approach future. Mesenchymal (MSCs) are ideal seed repairing many diseases. Paracrine secretion important pathway achieve effects, MSC-derived have shown provide similar functions MSCs. However, severe this study, (UCMSC)-derived injury cells. More importantly, exerted The outcomes work evidence as cell-free therapy strategy

Language: Английский

Citations

6

Current optimized strategies for stem cell-derived extracellular vesicle/exosomes in cardiac repair DOI
Rongrong Wu, Xinyang Hu, Jianan Wang

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2023, Volume and Issue: 184, P. 13 - 25

Published: Oct. 4, 2023

Language: Английский

Citations

5

Human Bone-Marrow-Derived Stem-Cell-Seeded 3D Chitosan–Gelatin–Genipin Scaffolds Show Enhanced Extracellular Matrix Mineralization When Cultured under a Perfusion Flow in Osteogenic Medium DOI Open Access
Gabriele Boretti, Emanuele� Giordano, Mariana Ioniţă

et al.

Materials, Journal Year: 2023, Volume and Issue: 16(17), P. 5898 - 5898

Published: Aug. 29, 2023

Tissue-engineered bone tissue grafts are a promising alternative to the more conventional use of natural donor grafts. However, choosing an appropriate biomaterial/scaffold sustain cell survival, proliferation, and differentiation in 3D environment remains one most critical issues this domain. Recently, chitosan/gelatin/genipin (CGG) hybrid scaffolds have been proven as suitable induce osteogenic commitment undifferentiated cells when doped with graphene oxide (GO). Some concern is, however, raised towards graphene-related material medical applications. The purpose work was thus check if potential CGG without added GO could be increased by improving medium diffusion culture differentiating cells. To aim, level extracellular matrix (ECM) mineralization evaluated human bone-marrow-derived stem (hBMSC)-seeded upon under perfusion flow dedicated custom-made bioreactor system. One week after initiating dynamic culture, histological/histochemical evaluations were carried out analyze early culture. analyses show enhanced ECM perfused compared static counterpart. results investigation reveal new perspective on efficient clinical applications GO.

Language: Английский

Citations

3