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Developing a Cell-Microcarrier Tissue-Engineered Product for Muscle Repair Using a Bioreactor System

Cartaxo, AL; Fernandes-Platzgummer, A; Rodrigues, CAV; Melo, AM; Tecklenburg, K; Margreiter, E; Day, RM; ... Cabral, JMS; + view all (2023) Developing a Cell-Microcarrier Tissue-Engineered Product for Muscle Repair Using a Bioreactor System. Tissue Engineering - Part C: Methods , 29 (12) pp. 583-595. 10.1089/ten.tec.2023.0122. Green open access

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Abstract

Fecal incontinence, although not life-threatening, has a high impact on the economy and patient quality of life. So far, available treatments are based on both surgical and nonsurgical approaches. These can range from changes in diet, to bowel training, or sacral nerve stimulation, but none of which provides a long-term solution. New regenerative medicine-based therapies are emerging, which aim at regenerating the sphincter muscle and restoring continence. Usually, these consist of the administration of a suspension of expanded skeletal-derived muscle cells (SkMDCs) to the damaged site. However, this strategy often results in a reduced cell viability due to the need for cell harvesting from the expansion platform, as well as the non-native use of a cell suspension to deliver the anchorage-dependent cells. In this study, we propose the proof-of-concept for the bioprocessing of a new cell delivery method for the treatment of fecal incontinence, obtained by a scalable two-step process. First, patient-isolated SkMDCs were expanded using planar static culture systems. Second, by using a single-use PBS-MINI Vertical-Wheel® bioreactor, the expanded SkMDCs were combined with biocompatible and biodegradable (i.e., directly implantable) poly(lactic-co-glycolic acid) microcarriers prepared by thermally induced phase separation. This process allowed for up to 80% efficiency of SkMDCs to attach to the microcarriers. Importantly, SkMDCs were viable during all the process and maintained their myogenic features (e.g., expression of the CD56 marker) after adhesion and culture on the microcarriers. When SkMDC-containing microcarriers were placed on a culture dish, cells were able to migrate from the microcarriers onto the culture surface and differentiate into multinucleated myotubes, which highlights their potential to regenerate the damaged sphincter muscle after administration into the patient. Overall, this study proposes an innovative method to attach SkMDCs to biodegradable microcarriers, which can provide a new treatment for fecal incontinence.

Type: Article
Title: Developing a Cell-Microcarrier Tissue-Engineered Product for Muscle Repair Using a Bioreactor System
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/ten.tec.2023.0122
Publisher version: http://dx.doi.org/10.1089/ten.tec.2023.0122
Language: English
Additional information: © Ana Luı´sa Cartaxo et al. 2023; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: CD56, TIPS PLGA microcarriers, fecal incontinence, myotube formation, skeletal derived muscle cells, Humans, Cell Culture Techniques, Fecal Incontinence, Quality of Life, Bioreactors, Muscles
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10184962
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