Disease Focus: Skeletal/Smooth Muscle disorders
Identification and Generation of Long Term Repopulating Human Muscle Stem Cells from Human Pluripotent Stem Cells
Research Objective We will molecularly and functionally define muscle stem cells in human muscle in development, juvenile and adult and develop strategies to generate the most regenerative muscle stem cells from hPSCs. Impact There is no clinically relevant cell endowed with continuous repopulation ability from hPSCs. This work could provide a cell therapy for muscle […]
Stimulating endogenous muscle stem cells to counter muscle atrophy
Research Objective Intramuscular delivery of two repurposed FDA approved drugs will activate resident muscle stem cells. This therapeutic strategy will augment regeneration and restore strength to atrophied muscles. Impact Currently effective treatments are lacking for localized muscle atrophy due to nerve injury (eg., Carpal Tunnel Syndrome) or immobilization after trauma or surgery (eg., hip or […]
CRISPR/Cas9 nanoparticle enabled therapy for Duchenne Muscular Dystrophy in muscle stem cells
Research Objective Gene correction of muscle stem cells Impact These studies will develop a gene editing based therapy for one of the most prevalent lethal childhood disorders called Duchenne Muscular Dystrophy. Major Proposed Activities To identify the best MSNP-CRISPR candidates for CRISPR/Cas9 plasmid delivery in vitro to muscle stem cells To identify the best MSNP-STEM […]
Prodrug innovation to target muscle stem cells and enhance muscle regeneration
Research Objective To target therapeutics to muscle stem cells, the building blocks of skeletal muscle. Impact Drugs, genes and gene editing strategies can be delivered directly to muscle stem cells to alleviate disease. Major Proposed Activities Synthetic peptides based on the ectodomains of Myomaker will be synthesized, with a fluorophore conjugated for tracking. Alternatively, anti-Myomaker […]
Generation of expandable, self-renewing muscle stem cells for Duchenne Muscular Dystrophy
Research Objective The goal of this proposal is to define protocols to generate expandable, self-renewing human muscle stem cells (MuSC) from hiPS cells for Duchenne Muscular Dystrophy disease modeling and therapeutics. Impact The integration of STAT3i with current approaches to derive myogenic cells from hiPS cells would enable the generation of self-renewing MuSC that are […]
Novel Platforms to Enhance In Vivo Delivery of Skeletal Muscle Progenitor Cells from Human Pluripotent Stem Cells
Research Objective Delivery of muscle stem cells presents a major roadblock for therapy. We explore novel approaches to increase the efficiency of delivering and monitoring muscle stem cells derived from hPSCs. Impact Development of enhanced monitoring and delivery platforms will greatly accelerate translational strategies aimed at delivering muscle stem cells for transplantation to patients with […]
Curing bladder cancer by replacing corrupted urothelium with differentiated hES cells
Research Objective The goal of the proposed research is to use human embryonic stem cells to generate bladder epithelial progenitor cells that can be used to replace a cancerous bladder epithelium in vivo. Impact The long-term goal of the proposed research is to cure bladder cancer. Successful completion of this work may indicate that transplantation […]
Autologous iPSC-based therapy for radiation induced bladder injury
Research Objective To explore if iPSC-based therapy can prevent bladder damage due to radiation therapy, thereby limiting the unintended consequences of treatments for prostate, gynecologic and colorectal cancers. Impact This therapy impacts cancer survivors by preventing the permanent debilitating urinary symptoms due to radiation therapy. Currently there are no therapies to prevent radiation bladder damage. […]
Examining the efficacy of GDF11 antibody as a rejuvenator of aged human muscle stem cell capacity and muscle repair .
Research Objective To examine the efficacy of blocking blood borne GDF11 activity to rejuvenate aged human muscle stem cell regenerative capacity. Impact This project will provide a proof-of-principle that GDF11 inhibition can boost aged human skeletal muscle repair, and facilitate its translational potential. Major Proposed Activities Determine GDF11 protein levels in human sera as a […]
Development of MyoDys45-55, a gene editing therapy for Duchenne muscular dystrophy
Translational Candidate A gene editing therapy for Duchenne muscular dystrophy that permanently removes a hotspot region of patient mutations to restore dystrophin. Area of Impact Duchenne muscular dystrophy (DMD), a fatal muscle wasting disease with no cure. Mechanism of Action Our therapy uses CRISPR/Cas9 gene editing to permanently remove a hotspot region of DMD patient […]