Evaluation of adipose-derived stem cells for tissue-engineered muscle repair construct-mediated repair of a murine model of volumetric muscle loss injury

Abstract

Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR–MDC constructs as previously reported.

Extracellular matrix scaffolds for treatment of large volume muscle injuries: A review

“…The addition of autologous or allogeneic muscle progenitor cells, satellite cells, mesenchymal stem cells, or adipose‐derived stem cells to ECM has been explored for VML treatment . Cell‐seeded ECM scaffolds seek to combine the proregenerative features of cellular and matrix factors to enhance overall regenerative capacity.…”

“…Most studies were conducted in rodents (88%); however, a few used larger species such as dogs, pigs, and rabbits (12%) . Muscles targeted for VML repair have included abdominal wall muscles (33%), cranial tibial (33%), latissimus dorsi (10%), quadriceps (10%), gastrocnemius/musculotendinous junction (8%), vastus lateralis , and peroneus tertius …”

“…Muscle progenitor cells (MPC) derived from muscle biopsies are challenging because of marked heterogeneity, phenotypic instability, and difficulty in expanding sufficient cell numbers . These cell types were compared for their ability to populate a porcine urinary bladder ECM construct in a mouse full‐thickness latissimus dorsi muscle model and were associated with histological evidence of regeneration . Although present across the scaffold surface, ASC were less frequently incorporated into new myofibers than were MPC.…”

Myogenic differentiation of primary myoblasts and mesenchymal stromal cells under serum-free conditions on PCL-collagen I-nanoscaffolds

“…These cells can differentiate spontaneously into skeletal myoblasts, expressing myogenic markers and forming multinucleated myotubes when co-cultured with myogenic cells [ 11 ]. Tissue-engineered muscle constructs incorporating ADSC have displayed skeletal muscle regeneration potential [ 12 ].…”

Adipose Stem Cell Translational Applications: From Bench-to-Bedside

“…Skeletal muscle is characterized by a remarkable regenerative capacity. However, if extensive damage exceeds the self-regenerating capacity of the muscle it can lead to the formation of irreversible fibrosis and scarring with significant loss of function [ 315 ]. In this context, benefit was gained by ASCs transplanted with a collagen hydrogel into the crushed tibial muscle [ 297 ].…”