Mesenchymal stromal cell spheroids in sulfated alginate enhance muscle regeneration.

Autor: Gionet-Gonzales MA; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA., Gresham RCH; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA., Griffin KH; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA; School of Veterinary Medicine, UC Davis, Davis, CA, USA., Casella A; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA., Wohlgemuth RP; Department of Neurobiology, Physiology and Behavior, UC Davis, Davis, CA, USA., Ramos-Rodriguez DH; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA., Lowen J; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA., Smith LR; Department of Neurobiology, Physiology and Behavior, UC Davis, Davis, CA, USA; Department of Physical Medicine and Rehabilitation, UC Davis Health, Sacramento, CA, USA., Leach JK; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA; Department of Biomedical Engineering, UC Davis, Davis, CA, USA. Electronic address: jkleach@ucdavis.edu.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2023 Jan 01; Vol. 155, pp. 271-281. Date of Electronic Publication: 2022 Nov 01.
DOI: 10.1016/j.actbio.2022.10.054
Abstrakt: The therapeutic efficacy of mesenchymal stromal cells (MSCs) for tissue regeneration is critically linked to the potency of the complex mixture of growth factors, cytokines, exosomes, and other biological cues that they secrete. The duration of cell-based approaches is limited by rapid loss of cells upon implantation, motivating the need to prolong cell viability and extend the therapeutic influence of the secretome. We and others demonstrated that the secretome is upregulated when MSCs are formed into spheroids. Although the efficacy of the MSC secretome has been characterized in the literature, no studies have reported the therapeutic benefit of in situ sequestration of the secretome within a wound site using engineered biomaterials. We previously demonstrated the capacity of sulfated alginate hydrogels to sequester components of the MSC secretome for prolonged presentation in vitro, yet the efficacy of this platform has not been evaluated in vivo. In this study, we used sulfated alginate hydrogels loaded with MSC spheroids to aid in the regeneration of a rat muscle crush injury. We hypothesized that the use of sulfated alginate to bind therapeutically relevant growth factors from the MSC spheroid secretome would enhance muscle regeneration by recruiting host cells into the tissue site. The combination of sulfated alginate and MSC spheroids resulted in decreased collagen deposition, improved myogenic marker expression, and increased neuromuscular junctions 2 weeks after injury. These data indicate that MSC spheroids delivered in sulfated alginate represent a promising approach for decreased fibrosis and increased functional regeneration of muscle. STATEMENT OF SIGNIFICANCE: The therapeutic efficacy of mesenchymal stromal cells (MSCs) for tissue regeneration is attributed to the complex diversity of the secretome. Cell-based approaches are limited by rapid cell death, motivating the need to extend the availability of the secretome. We previously demonstrated that sulfated alginate hydrogels sequester components of the MSC secretome for prolonged presentation in vitro, yet no studies have reported the in situ sequestration of the secretome. Herein, we transplanted MSC spheroids in sulfated alginate hydrogels to promote muscle regeneration. MSC spheroids in sulfated alginate decreased collagen deposition, improved myogenic marker expression, and increased neuromuscular junctions. These data indicate that MSC spheroids delivered in sulfated alginate represent a promising approach for decreasing fibrosis and increasing functional muscle regeneration.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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