Clinical Translation

The CTRL’s main focus is to identify critical barriers to the clinical translation of musculoskeletal research efforts investigated within the SCRC, and to develop methods for overcoming these barriers.

Lab Personnel

• Fabrisia Ambrosio, Ph.D., MPT, Lab Co-Director
• Vonda Wright, M.D., Lab Co-Director
• Ricardo Ferrari, P.T.
• Michelle Witt
• Josh Plassmeyer
• Giovanna Ferrari
• Elke Brown

Lab Projects

Therapeutic synergy of stem cell transplantation and motor unit activation to rescue dystrophic muscle:

Muscle cells function to contract. It is well known that environmental cues resulting from muscle injury or exercise stimulate resident satellite cells to proliferate and differentiate in order to form multinucleated myotubes. However, the mechanism underlying the signaling of stem cells remains largely unknown, and an improved understanding of the environmental cues promoting stem cell expansion and differentiation is a critical step toward using these promising cells for clinical applications.

In vitro, our laboratory has shown that mechanical strain induces an increased proliferation and increased regenerative capacity of muscle derived stem cells (MDSCs). In vivo, it is generally accepted that exercise is beneficial for improving skeletal muscle quality in healthy skeletal muscle through increases in the satellite cell count. Along these lines, we propose that, when subjected to an exercise protocol, there will be an increased contribution of transplanted MDSCs to the physiological functioning of the dystrophic muscle as a whole.

This project is unique in that it introduces rehabilitation approaches early in the development of regenerative medicine strategies to improve skeletal muscle function. The translation of this biological therapy for the treatment of DMD is promising, as MDSCs are already undergoing clinical trials for the treatment of incontinence and chronic heart failure.

The effect of gender and age on stem cell transplantation capacity for tendon tissue engineering:

Tendon injuries are common. The successful resolution of degenerative tendon injuries can be limited by a number of factors such as inherently slow healing kinetics, decreased strength and elasticity following healing, and a high injury recurrence rate. Although surgical advances continue to develop in tendon repair and reconstructive surgery, drawbacks persist. Increased healing potential may be realized via tissue engineering using stem cells.

Many cellular factors influence stem cell regenerative capacity in a tissue specific manner including stem cell and host sex, and tissue age. Although orthopaedics has recognized sex and age-related differences in the demographics and natural history of many injury states, few studies have evaluated these differences on the cellular level.

Via age- and sex-matched/mismatched experiments, we are examining the interaction of stem cell age and sex in vitro. Additionally, we are examining how the in vitro differences in stem cell response to physiologic stress translate into differences in regenerative capacity using an in vivo model. These experiments may provide a greater understanding of the specific influences of sex and age on tendon healing and may translate into more effective healing modalities for tendon injuries.

A loading-induced increase in capillarity preserves skeletal muscle regenerative capacity in aged rodents:

Aged skeletal muscle is characterized by muscle weakness, increased susceptibility to injury, and a decreased regenerative capacity. These factors may contribute to decreased balance, increased likelihood for falls, and decreased overall function in the elderly. The ability of muscle for hypertrophy or regeneration after injury is dependent on satellite cell activation and proliferation. Through this pilot study, we intend to take preliminary steps towards understanding the underlying mechanism by which exercise results in the maintenance and/or enhancement of muscle mass and regenerative capacity in aging skeletal muscle.

In this study we are investigating the role of capillarization on the loading-induced increase in satellite cell count in young and aged mice, as well as the association of a loading-induced increase in muscle capillarization and improvements in the regenerative capacity of aged skeletal muscle. Finally, we are investigating whether there is a mediation by capillarization for satellite cell count and regenerative capacity.

Achieving a mechanistic understanding of the beneficial effects of loading on muscle will provide the framework for future studies in the development of targeted rehabilitation strategies to improve skeletal muscle quality in elderly individuals. Specifically, we will investigate clinically applicable methods to stimulate angiogenesis for the maintenance of muscle mass, enhancement of muscle healing, and improvement of functional mobility in the elderly population.

<<Back to Divisions
<<Back to Molecular Therapeutics Lab
Stem Cell Ecology Lab>>