Muscle tissue has the ability for spontaneous regeneration, recovering from stress and strain. However, serious incidents such as trauma or tumor resection, which causes volumetric muscle loss (VML), creates damage far from the muscles' natural capacity to recover.
A new study proposes a new technique for artificial muscle regeneration, using direct cell reprograming methods together with a natural-synthetic hybrid scaffolding. It was successfully used in a VML treatment in a mouse model. Details of the novel protocol are published in the latest Advanced Materials.
Advancing VML Treatments
In currently existing VML treatments, the method usually involves surgical interventions that rely on autologous muscle flaps - samples coming from other parts of the same person - which are grafter and later guided to recovery by physical therapy programs. Unfortunately, surgical procedures could result in reduced muscular function. Worse, there have been cases when the operation leads to graft failure - when the host rejects the donor tissues. This creates the interest for therapeutic alternatives that could offer better muscle loss recovery odds.
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One of the potentials explored is the induction of de novo regeneration of skeleton muscles by integrating transplanted cells. This approach has seen the use of different cell types - satellite cells or muscle stem cells, myoblasts, and even mesenchymal stem cells (adult stem cells in an extracellular matrix). However, its feasibility has been largely hampered by poor cell availability, invasive muscle biopsies, and the required long-term maintenance. Up to billions of mature cells might be required to deliver observable therapeutic effects.
Another critical parameter is the total control of the microenvironment surrounding the injury site. Successful VML treatments must ensure that the introduced cells could adapt to the needed muscle tissues with compatible and reliable structures. While various natural and synthetic materials have encouraged recovery, there remains a few problems concerning tissue scaffolding. Natural scaffolds have high cell recognition and affinity for binding; they start failing in mechanical robustness for large lesions requiring long-term support. On the other hand, synthetic scaffolding exhibits better mechanical properties yet suffers from cell recruitment and poor host tissue integration.
Using Direct Cell Programming and Hybrid Scaffolds
Researchers' strategy in the new VML treatment technique involves direct cell reprogramming or direct cell conversion. It offers cell therapy by allowing the rapid generation of target cells using autologous cells derived from a tissue biopsy. In this method, the usually-used cell types are fibroblasts, commonly found in connective tissues and used in wound regeneration. With the use of additional transcription factors, fibroblasts can be turned into induced myogenic progenitor cells (iMPC), especially since recovered fibroblasts are not yet terminally-differentiated cells, allowing them to be engineered.
As for the structural support for the introduced muscle cells, researchers used polycaprolactone (PCL). The highly biocompatible material also allows for the fabrication of porous scaffolding. Conventional fabrication methods such as salt leaching, however, only allow for closed porous structure. To achieve the porosity required to make PCL scaffolds work, researchers augmented salt leaching with thermal drawing, resulting in customized scaffolds made from PCL fibers.
It resulted in muscle fiber constructs that have a mechanical stiffness close to muscle tissues, enhanced muscle differentiation, and exhibited in vitro elongated muscle alignment. However, Professor Cho Seung-Woo, who led the study, noted that "further studies are required to elucidate the mechanisms of muscle regeneration by our hybrid constructs and to empower the clinical translation of cell-instructive delivery platforms."
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