This Phase II SBIR extends a Phase I proof of principle study originally submitted in response to RFA-AG-12-009 entitled T1 Translational Research on Aging from the NIA. In Phase I, LaCell has documented pre-clinical safety and efficacy of a novel adipose derived cell therapy for the treatment of pressure ulcers in young and old mice. The injection of murine ASC significantly accelerated and enhanced pressure ulcer repair in female mice of both age groups in a dose dependent manner as evidenced by the rate of wound closure, re-epithelialization, skin tissue architecture, inflammatory cell infiltratin and expression of molecular biomarkers. LaCell's studies pave the way for clinical translation and regulatory approval of ASC therapies. While it is well established that the prevention of pressure ulcers requires labor-intensive nursing care, patients in assisted living centers and nursing homes remain at high risk for developing pressure ulcers. Over 70% of pressure ulcers occur in Americans over the age of 70 and their hospital costs exceed $11 billion annually. Current treatment of pressure ulcers relies primarily on surgical debridement, hyperbaric oxygen, and negative pressure devices. The adipose derived- cell based therapies have the potential to substantially reduce the length of hospitalization and associated health care costs for pressure ulcer patients. LaCell has partnered with a Tissue Genesis, Inc., to use their established ICellator device to obtain clinical grade human SVF cells. This strategic partnership will accelerate the clinical translation of LaCell's cell therapeutic to the marketplace.
Specific Aims (SA) will address pharmacotoxicology regulatory concerns in murine models and serve as a definitive protocol to the Food and Drug Administration for an Investigational Device Exemption in the case of SVF cells (SA1) and a Biologics License Application in the case of ASC (SA2). Each SA will evaluate the concentration dependency of human SVF cells and ASC in the treatment of a murine pressure ulcer therapy in immunodeficient and immunocompetent mice of both sexes; both young and old immunocompetent mice will be evaluated. Injection of PBS alone or with human dermal fibroblasts will serve as negative controls while topical application of the FDA approved diabetic wound therapeutic, beclapermin (PDGF-BB) will serve as a positive control. Quantitative outcomes will include rate of wound closure, inflammatory cell infiltration, pro-inflammatory cytokine expression, and immunohistochemical detection of human cells in situ. Since pressure ulcer treatment accounts for 1- 4% of the total health care budget in developed nations, LaCell's developing technologies have considerable market potential.
The elderly are at high risk for the development of pressure ulcers, a life threatening condition that remains a major health care burden in the U.S. With its background in adipose stromal/stem cell biotechnology, LaCell, its strategic partner, Tissue Genesis, Inc., and its academic collaborators are uniquely positioned to address this unmet medical need. LaCell has peer review published Preliminary Data supporting the efficacy and safety of an adipose stromal/stem cell therapy for pressure ulcers. LaCell's approach has the potential to accelerate and improve the rate of wound closure and long-term recovery. This Phase II proposal will extend on LaCell's initial findings and develop essential pre-clinical data to advance adipose-derived cell therapies and translate them into an FDA approved clinical trial. LaCell's stem cell products are relevant to geriatric medicine and will improve healthcare for the rapidly growing number of elderly Americans.