Wake Forest Institute for Regenerative Medicine (WFIRM) researchers have developed a “point-of-care” processing method to create uniformly sized muscle fiber fragments that could be implanted into tissue to restore function to treat muscle loss due to traumatic injury or congenital defects.
The current treatment standard for such muscle loss is grafting of muscle flaps from the patient, but availability of graft tissue is limited and significant scarring can occur at the graft site. Alternatively, muscle fiber therapy has been attempted to treat muscle injury by transplanting single fibers into the defect site but this method has resulted in irregularly organized long fibers with low survivability due to delay in vascular and neural integration. Therapeutic efficacy was limited as a result.
The WFIRM team was looking for a solution to address these issues as well as the time and cost limitations of engineering muscle tissue for implantation. Injecting uniformly sized small muscle fiber fragments, they theorized, would induce integration of the fragments within the host muscle tissue.
“The processing method we developed will help the fragments more readily integrate with the host vascular and neural networks to restore function to patients,” said senior study author Anthony Atala, MD, director of WFIRM.
For the recently published study, the research team created several pre-clinical injury models to mimic muscle atrophy, muscle defect and stress urinary incontinence. To do so, muscle tissue was harvested from donor tissue, minced and processed in collagen breaking solution to obtain individual fragments. Subsequently, the solution was filtered to collect uniformly sized muscle fiber fragments that can be used for treatment.
he fragments were labeled with a fluorescent dye for tracking and injected into the models’ tissues. Four weeks after transplantation, the muscle fiber fragments had reassembled and integrated with the vascular and neural system of the host tissue.
Results for all three model types, were promising. In the muscle atrophy model, the fragments reassembled and organized into long muscle fibers that integrated at the recipient site. The muscle defect model showed enhanced muscle mass and function restoration. For the urinary incontinence model, sphincter contraction force was evaluated and it was found that the fragments had successfully engrafted into the damaged site and integrated with host muscle.
Current available treatments for urinary incontinence can often cause complications. Previous WFIRM cell therapy research using muscle progenitor cells to treat urinary incontinence is a promising option, but it involves culturing and expanding cells outside the body which requires lengthy time and resources.
“One of the interesting approaches studied using the muscle fiber fragment therapy is to treat urinary incontinence which is a major health issue that affects one in three individuals who have some loss of bladder control at some point in their lives,” said co-author James Yoo, MD, PhD, professor of regenerative medicine at WFIRM.
The simple processing steps involved with this technology platform, said Atala, were developed as a “point of care” treatment option “where viable tissue can be harvested, processed and applied to the patient in the same operating room setting.”
The researchers caution that there are several limitations that need to be addressed such as efficiency of the muscle fiber fragments isolation process from the donor muscle tissue as well as further optimization of the process to increase the yield of the fragments.
“Our study shows that this method may be most suitable for treating small and critical muscle defects, such as craniofacial muscle defects or the sphincter muscles related to incontinence where small amounts of donor tissue could achieve functional recovery,” Yoo said.
Co-authors include In Kap Ko, Eun Sang Yoo, Sang Mi Park, Bu-Kyu lee, Ji Hyun Kim, all of WFIRM. Authors Atala, Yoo and Ko are inventors on patent rights related to this work owned by Wake Forest University Health System. The patents, whose value may be affected by publication, have the potential to generate royalty income in which the inventors would share.
This research was funded by the Department of Defense (Grant No. W81XWII-08-1-0333, awarded by the DoD-Orthopedics Trauma Research Program). The full paper can be accessed at the Wilkey Online Library.