DOMICELL INC. — Department of Health and Human Services SBIR Phase I: NHLBI

Description

Project Summary Despite advances in the treatment of acute myocardial infarction MI many patients still experience loss of cardiac muscle with subsequent adverse cardiac remodeling and heart failure Stem cell therapy administered early after MI was designed to reduce heart failure by decreasing cell death and increasing the regeneration of new cardiac muscle and vascular cells However most trials achieved only modest clinical benefits Growing evidence suggests that many of the beneficial effects of stem cells are due to exosomes and other paracrine factors PFs they secrete These factors increase angiogenesis decrease apoptosis potentiate cell proliferation promote cell migration and as a result andquot turn onandquot and andquot turn upandquot the bodyandapos s intrinsic repair capac ity Delivery of these stem cell factors and their sustained presence at the injured site could limit damage effect repair and produce a significant and lasting clinical benefit However delivery vehicles that can sense the evolving needs of injured tissue and in response deliver the large and varying array of required factors have not been available We created the Stem Cell Implantable Bioreactor SCIB a novel removable platform for in vivo production and delivery of stem cell PFs to achieve this objective The SCIB is placed in a central vein after reperfusion therapy for acute MI and shelters stem cells within a protective semi permeable pouch shielding them from washout and immune attack but allowing nutrients to enter and PFs to pass freely into the circulation and to the injured tissue Stem cells in the SCIB act as andquot factoriesandquot that sense host signals and in response produce the entire library of potentially hundreds of PFs in the right sequence concentration combination and duration required for healing The first generation SCIB favorably reduced adverse cardiac remodeling after an anterior MI in pigs but was impermeable to exosomes had a limited stem cell capacity and was not manufactured using clinical grade materials We formed Domicell LLC to develop a refined SCIB for human testing and commercialize the technology In this SBIR Phase application we propose critical in vitro and in vivo studies that will support the development of a second generation SCIB using clinical grade materials with a higher stem cell capacity and permeability to all PFs including exosomes At the conclusion of the proposed SBIR Phase studies Domicell LLC will have a clinical grade SCIB product that will support a pivotal pre clinical large animal study in SBIR Phase the results of which will be used to apply to the FDA for first in man clinical trials In the long term Domicell LLC envisions that cell therapy based on implantable bioreactors will become a fundamentally new approach to deliver on demand cell derived PFs for the treatment of both cardiac and non cardiac diseases Project Narrative Stem cell therapy after a heart attack is designed to reduce heart failure but most trials achieved only modest clinical benefit Evidence now suggests that many of the favorable effects of stem cells are due to exosomes and other paracrine factors they secrete We designed built and tested the Stem Cell Implantable Bioreactor SCIB a novel platform for in vivo production and delivery of stem cell paracrine factors and we are seeking SBIR funds to develop a human ready product for clinical testing