Adipose-Derived Stromal/Stem Cell Therapy for Pressure Ulcers

描述（由申请人提供）：该I期SBIR响应NIA的RFA-AG-12-009“T1衰老转化研究”，探索新的基于细胞的治疗方法来治疗老年人压疮和全层皮肤伤口。虽然众所周知，压疮的预防需要劳动密集型护理，但生活在辅助生活中心和疗养院的患者仍然有患压疮的高风险。事实上，超过70%的压疮发生在70岁以上的美国人身上，他们的住院费用每年超过110亿美元。目前压疮的治疗主要依靠手术清创、高压氧、生长因子和负压装置。这项“原理验证”研究将使用小鼠模型来验证LaCell的假设，即脂肪来源的基质/干细胞（ASC）疗法将加速和改善老年人压疮的愈合。研究将在年轻（3-4个月）和年老（24个月）C57Bl/6雄性小鼠中进行，使用瘦素受体缺陷（db/db）肥胖糖尿病小鼠（3-4个月）作为阳性对照。将在每只小鼠的背部制造双侧全层皮肤伤口。这些将被一个甜甜圈形状的硅夹板保护，以防止伤口边缘的自发收缩。这将允许伤口上皮化和愈合率的准确测量。从转绿色荧光蛋白（GFP）的C57Bl/6小鼠中分离脂肪基质/干细胞（ASC）。在每只动物中，将GFP+ ASC注射到一个全层缺损的伤口床上，同时将相应的伤口注射磷酸盐缓冲盐水作为对照。各组动物将在术后1、3和10天采收。定量实验结果将探讨ASC影响修复的机制，包括上皮化率、伤口愈合、细胞因子和基质金属蛋白酶表达以及免疫细胞浸润。这些结果将决定基于ASC的治疗加速老年人压疮和全层皮肤伤口修复的可行性和有效性。I期将为未来II期研究中小鼠和人ASC的药代动力学和毒理学测试奠定基础。此外，它们将为与美国食品和药物管理局进行ind前的详细讨论提供基础。LaCell LLC是一家由脂肪基质/干细胞应用于再生医学的领先研究人员和发明家创立的生物技术公司。作为顾问，LaCell得到了整形外科和伤口愈合领域专家的帮助。

DESCRIPTION (provided by applicant): This Phase I SBIR, responding to RFA-AG-12-009 entitled "T1 Translational Research on Aging" from the NIA, explores novel cell-based therapeutic approaches to the treatment of pressure ulcers and full thickness skin wounds in the elderly. Although 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. In fact, 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, growth factors, and negative pressure devices. This "proof of principle" study will use a murine model to test LaCell's hypothesis that adipose-derived stromal/stem cell (ASC) therapy will accelerate and improve pressure ulcer healing in the elderly. Studies will be conducted in young (3-4 month) and old (24 month) C57Bl/6 male mice using leptin receptor deficient (db/db) obese diabetic mice (3-4 month) as positive controls. Bilateral full thickness skin wounds will be created dorsally on each mouse. These will be protected by a silicon splint in the shape of a donut to prevent spontaneous retraction of the wound edges. This will allow for accurate measurements of the wound epithelialization and healing rates. Adipose stromal/stem cells (ASC) will be isolated from C57Bl/6 mice transgenic for the green fluorescent protein (GFP). In each animal, GFP+ ASC will be injected into the wound bed of one full thickness defect while the corresponding wound, injected with phosphate buffered saline, will serve as a control. Groups of animals will be harvested after 1, 3, and 10 days post-operatively. Quantitative experimental outcomes will address the mechanisms underlying the ASC impact on repair that will include rates of epithelialization, wound closure, cytokine and matrix metalloproteinase expression, and immune cell infiltration. These outcomes will determine the feasibility and efficacy of ASC based therapies to accelerate the repair of pressure ulcers and full thickness skin wounds in the elderly. Phase I will lay the foundation for future pharmacokinetic and toxicological testing of both murine and human ASC in Phase II studies. Additionally, they will provide the basis for detailed pre-IND discussions with the Food and Drug Administration. LaCell LLC is a biotechnology company founded by leading investigators and inventors in the application of adipose stromal/stem cells to regenerative medicine. As consultants, LaCell has enlisted the assistance of experts in the field of plastic surgery and wound healing. PUBLIC HEALTH RELEVANCE: The elderly are at high risk for the development of pressure ulcers, a debilitating and life threatening condition that remains a major health care burden in the U.S. LaCell proposes to develop an adipose stromal/stem cell therapy for pressure ulcers. This approach has the potential to accelerate and improve the rate of wound closure and long-term recovery. The outcomes of this focused "proof of principle" pre-clinical study have relevance to a clinical issue of unique importance to geriatric medicine in the U.S. and abroad. With its background in adipose stromal/stem cell biotechnology, LaCell and its consultants are uniquely positioned to address this unmet medical need.