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Engineering an Injectable Muscle-Specific Microenvironment for Improved Cell Delivery Using a Nanofibrous
Nikhil Rao1, Gillie Agmon1, Matthew T Tierney
1Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego , La Jolla, California 92037, United States.
ACS Nano
|March 22, 2017
Summary
Engineering a muscle microenvironment using extracellular matrix hydrogels and fibroblasts significantly improves the survival and vascularization of transplanted skeletal muscle progenitors, offering a promising therapeutic approach.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Tissue Engineering
Background:
- Skeletal muscle progenitor cell transplantation shows promise for treating diseases affecting vasculature and muscle, such as peripheral artery disease.
- Limited success is attributed to poor cell survival caused by needle injection, ischemic host environments, immune responses, and lack of biophysical cues.
- Developing strategies to enhance cell survival and integration is crucial for effective cell-based therapies.
Purpose of the Study:
- To engineer a muscle-specific microenvironment to improve the viability and maturation of transplanted skeletal muscle progenitors.
- To evaluate the efficacy of this engineered microenvironment in enhancing cell survival, engraftment, and vascularization in vivo.
Main Methods:
- Utilized a nanofibrous decellularized skeletal muscle extracellular matrix hydrogel combined with skeletal muscle fibroblasts to create an engineered microenvironment.
- Assessed myoblast viability and maturation in vitro within this engineered environment.
- Evaluated the in vivo outcomes, including cell survival, engraftment, and vascularization, following transplantation.
Main Results:
- The engineered muscle-specific microenvironment significantly improved myoblast viability and maturation in vitro.
- In vivo studies demonstrated enhanced survival and engraftment of transplanted cells.
- Increased perfusion and vascularization were observed in the host tissue, indicating successful integration and therapeutic effect.
Conclusions:
- A combinatorial delivery system that recapitulates the native tissue microenvironment can overcome barriers to successful cell delivery to skeletal muscle.
- Engineering the microenvironment is a viable strategy to enhance the therapeutic potential of skeletal muscle progenitor cell transplantation.
- This approach holds promise for treating conditions characterized by vascular and skeletal muscle damage.
