Harnessing the synergy of perfusable muscle flap matrix and adipose-derived stem cells for prevascularization and macrophage polarization to reconstruct volumetric muscle loss.

Autor:	Zhang Q; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Chiu Y; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Chen Y; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.; Department of Plastic Surgery, Chinese PLA General Hospital, Beijing, 100853, China., Wu Y; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Dunne LW; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Largo RD; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Chang EI; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Adelman DM; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Schaverien MV; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Butler CE; Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Jazyk:	angličtina
Zdroj:	Bioactive materials [Bioact Mater] 2022 Nov 04; Vol. 22, pp. 588-614. Date of Electronic Publication: 2022 Nov 04 (Print Publication: 2023).
DOI:	10.1016/j.bioactmat.2022.10.023
Abstrakt:	Muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful engraftment. We developed porcine stomach musculofascial flap matrix (PDSF) comprising extracellular matrix (ECM) and intact vasculature. PDSF had a dominant vascular pedicle, microcirculatory vessels, a nerve network, well-retained 3-dimensional (3D) nanofibrous ECM structures, and no allo- or xenoantigenicity. In-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins (e.g., collagens, glycoproteins, proteoglycans, and ECM regulators) that, as shown by Gene Ontology term enrichment analysis, are functionally related to musculofascial biological processes. Moreover, PDSF-human adipose-derived stem cell (hASC) synergy not only induced monocytes towards IL-10-producing M2 macrophage polarization through the enhancement of hASCs' paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts (HSMMs) and human umbilical vein endothelial cells (HUVECs) in static triculture conditions. Furthermore, PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs, which integrated with PDSF and induced the maturation of vascular networks in vitro . In a xenotransplantation model, PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T cells. In a volumetric muscle loss (VML) model, prevascularized PDSF augmented neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue formation. These results indicate that hASCs' integration with PDSF enhances the cells' dual function in immunomodulation and angiogenesis. Owing in part to this PDSF-hASC synergy, our platform shows promise for vascularized muscle flap engineering for VML reconstruction. (© 2022 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu