Adipose-Derived Stromal/Stem Cell Therapy for Pressure Ulcers

脂肪源性基质/干细胞治疗压疮

基本信息

批准号：
8368987
负责人：
Jeffrey Martin Gimble
金额：
$ 18.6万
依托单位：
LACELL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8368987
关键词：
Accounting Address Adipose tissue Age Age-Years Aging American Animals Assisted Living Facilities Beds Bilateral Biochemical Biomedical Research Biotechnology Budgets Bulla Care given by nurses Cell Therapy Cells Clinic Clinical Collagen Debridement Decubitus ulcer Defect Dependency Developed Countries Development Devices Diabetes Mellitus Diabetic mouse Dose Drug Kinetics Economic Burden Elderly Erythema Foundations Future Geriatrics Green Fluorescent Proteins Growth Factor Harvest Healed Healthcare Home environment Hospital Costs Hospitals Human Hyperbaric Oxygen Immobilization Immune In Vitro Incidence Infiltration Inflammatory Intellectual Property Legal patent Life Literature Matrix Metalloproteinases Measurement Medical Modeling Mus Nursing Homes Obesity Operative Surgical Procedures Outcome Patients Peripheral Vascular Diseases Pharmacology and Toxicology Phase Phosphate Buffer Plastic Surgical Procedures Positioning Attribute Pre-Clinical Model Prevention Publications Rattus Recovery Regenerative Medicine Research Personnel Risk Rodent Safety Saline Severities Shapes Silicon Skin Small Business Innovation Research Grant Solid Splint Device Stem cells Testing Therapeutic Thick Transgenic Mice Transgenic Organisms Translating Translational Research Translations Treatment Protocols Trichrome stain method Ulcer United States Food and Drug Administration Wound Healing age related base bench to bedside care burden cohort commercialization cytokine db/db mouse demographics diabetic efficacy trial experience healing high risk improved in vivo leptin receptor male novel phase 2 study preclinical study pressure prevent regenerative repaired stem cell biology stem cell technology stem cell therapy wound

项目摘要

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.

描述（由申请人提供）：该 I 期 SBIR 响应 NIA 题为“T1 衰老转化研究”的 RFA-AG-12-009，探索新的基于细胞的治疗方法来治疗压疮和全层皮肤老年人的伤口。尽管众所周知，预防压疮需要劳动密集型护理，但辅助生活中心和疗养院的患者仍然面临着发生压疮的高风险。事实上，超过 70% 的压疮发生在 70 岁以上的美国人身上，他们每年的住院费用超过 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测试 LaCell 的假设，即脂肪源性基质/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）和老年（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产生双侧全层皮肤伤口。这些将由甜甜圈形状的硅夹板保护，以防止伤口边缘自发回缩。这将允许准确测量伤口上皮化和愈合率。将从绿色荧光蛋白 (GFP) 转基因的 C57Bl/6 小鼠中分离出脂肪基质/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中，而注射磷酸盐缓冲盐水的相应伤口将作为对照。术后 1、3 和 10 天后收获各组动物。定量实验结果将解决 ASC 对修复影响的机制，包括上皮化率、伤口闭合、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 的疗法加速老年人压疮和全层皮肤伤口修复的可行性和有效性。第一阶段将为未来第二阶段研究中小鼠和人类 ASC 的药代动力学和毒理学测试奠定基础。此外，它们还将为与食品和药物管理局进行详细的 IND 前讨论提供基础。 LaCell LLC 是一家生物技术公司，由脂肪基质/干细胞在再生医学应用方面的领先研究人员和发明家创立。作为顾问，LaCell 寻求了整形外科和伤口愈合领域专家的帮助。公共健康相关性：老年人患压疮的风险很高，压疮是一种使人衰弱并危及生命的疾病，在美国仍然是主要的医疗负担。LaCell 建议开发一种用于压疮的脂肪基质/干细胞疗法。这种方法有可能加速和提高伤口闭合速度和长期恢复速度。这项重点“原理证明”临床前研究的结果与对美国和国外老年医学具有独特重要性的临床问题相关。凭借其在脂肪基质/干细胞生物技术方面的背景，LaCell 及其顾问在解决这一未满足的医疗需求方面拥有独特的优势。