Rima Gandlin, MS, Ph.D
Under the direction of Dr. Huard, the current focus of the Growth and Development Laboratory is the characterization of the relationship of the biomechanical, morphological and molecular aspects of the musculoskeletal system that pertain to tissue growth and maturation. Recently, research within the laboratory has focused on muscle-based gene therapy and tissue engineering for application to the musculoskeletal system, mainly as related to Duchenne Muscular Dystrophy and orthopedic diseases and injuries. Currently, researchers are persuing methods of characterizing novel population of muscle derived stem cells as they explore their potential uses in gene therapy and tissue engineering application for regenerative medicine. Using this technology, researchers within the lab are searching for novel ways to repair, replace, reconstruct, and regenerate damaged, diseased or absent tissues.

General highlights of the research conducted within the lab include:

  • Examining the biology of muscle derived stem cells and their potential uses in gene therapy and tissue engineering applications for Musculoskeletal Tissue regeneration.
  • Development of new biological approaches based on muscle derived stem cells to improve tissue healing and musculoskeletal, such as skeletal muscle bone healing, cartilage, ligament, meniscus.
  • Applying this technology to various forms of urological dysfunction such as stress incontinence and bladder dysfunction.
More specifically, Dr. Huard and those working in the Growth and Development Laboratory have come to focus their efforts on a several disorders in particular. These include Duchenne Muscular Dystrophy, muscle injury repair, limb lengthening, Arthritis and joint injuries and overcoming rejection in gene transfer. For more information regarding the Growth and Development Laboratory, please go to www.pitt.edu/~huardlab.

Duchenne Muscular Dystrophy
Researchers are focusing on fundamental research in muscle growth as well as in the development of applications of gene delivery systems to muscle in order to eventually apply this technology to dystrophin delivery to Duchenne Muscular Dystrophy (DMD) muscles. Efforts are aimed at defining those barriers to viral transduction of mature muscle, then investigating methods by which the barriers can be overcome. The proposed research should define and eliminate one of the major hurdles facing the application of gene therapy to DMD patients.

Muscle Injury Repair
Scientific projects are under investigation in the laboratory in order to characterize the efficiency of myoblast transplantation and autologous myoblast transfer as gene delivery systems for skeletal muscle. The development of approaches capable of improving muscle growth and regeneration also may be amenable for the improvement of muscle healing following muscle injuries. These muscle injuries are very frequent in sports medicine, and research is being pursued in our laboratory in regatrds to the development of models for different muscle injuries including, laceration, contusion and tears to increase our understanding of the cells' ability to recover. Also,many trophic factors are under investigation for their ability to promote cellular proliferation and differentiation, including: myoblasts, chondrocytes, ligament cells and meniscal cells. The characterization of trophic factors that enhance the myoblast proliferation and differentiation may be used in the future to improve the healing of such tissues following injury.

Limb Lengthening
Another major emphasis of the laboratory is to characterize the muscle behavior during limb lengthening. The aim is to investigate whether limb lengthening promotes muscle growth and/or a stretching process of the muscle fibers. Experiments suggest that induction of artificial muscle growth with trophic factors can be successful in preventing muscle contractures during limb lengthening. Researchers are investigating the ability of several trophic factors to promote muscle growth in cell culture (myoblast proliferation), to eventually deliver these trophic factors intramuscularly. Eventually, this project may require gene transfer procedures for delivering these trophic factors to the limb lengthened muscle.

Arthritis and Joint Injuries
During the last year, researchers have started some projects related to the application of new strategies to deliver genes to the joint. Recently, a project has been started aimed at determining whether muscle cells can be used as an alternative vehicle for gene transfer to the joint.

Overcoming Rejection in Gene Transfer
Researchers are also engineering cells capable of expressing various immuno-tolerant molecules such as, vIL-10, TGF-b, FasL and CTLA4Ig in an effort to bypass the immunological problems and eventually allow a persistent gene transfer to skeletal muscle and the joint.