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：
9339502
负责人：
Jeffrey Martin Gimble
金额：
$ 60.99万
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 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9339502
关键词：
Address Adipose tissue Age Age-Years Aging Allogenic American Animal Model Architecture Assisted Living Facilities Biological Assay Biotechnology Blood Vessels Brain Budgets C57BL/6 Mouse Care given by nurses Cell Fraction Cell Separation Cell Therapy Cells Clinical Clinical Data Clinical Trials Collaborations Data Debridement Decubitus ulcer Dependency Dermal Detection Developed Countries Developing Countries Development Devices Diabetic wound Distant Dose Economics Elderly Etiology FDA approved Female Fibroblasts Flow Cytometry Foundations Funding Geriatrics Grant Health Care Costs Healthcare Heart Histology Hospital Costs Hospitalization Hour Human Hyperbaric Oxygen Immunocompetent In Situ In Vitro Infiltration Inflammatory Injection of therapeutic agent Injury Investigation Ischemia Joints Kidney Laboratories Length Licensing Life Link Liver Lung Lymphangiogenesis Malnutrition Manufacturer Name Manuscripts Medical Memorial Sloan-Kettering Cancer Center Molecular Profiling Monitor Morphology Mus Natural regeneration Nursing Homes Operative Surgical Procedures Organ Outcome Patients Peer Review Periodicity Phase Pilot Projects Positioning Attribute Procedures Process Protocols documentation Publishing Publishing Peer Reviews Quadriplegia Quality of life Quantitative Reverse Transcriptase PCR Recovery Reperfusion Therapy Reporting Research Design Risk SCID Beige Mouse Safety Skin Skin Temperature Skin Tissue Small Business Innovation Research Grant South Korea Spinal cord injury patients Stem cells Surface Surveys System Technology Temperature Testing Therapeutic Time Tissues Topical application Translating Translational Research Ulcer United States Food and Drug Administration Universities Validation age group angiogenesis base bench to bedside care burden clinical translation cost cytokine experience healing high risk improved mRNA Expression male man medical attention meetings migration molecular marker mouse model novel platelet-derived growth factor BB point of care pre-clinical preclinical study pressure pressure ulcer prevention public health relevance regenerative repaired response sex skin regeneration stem cell therapy wound wound closure

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由适用提供）：此II阶段SBIR扩展了最初是针对NIA的RFA-AG-12-009提交的主要研究证明的。在第一阶段，拉塞尔（Lacell）记录了一种新型脂肪衍生的细胞疗法的临床前安全性和效率，用于治疗年轻小鼠和老鼠的压溃疡。两种年龄段的雌性小鼠的鼠类ASC的注射显着加速并增强了压疮修复，这是受伤闭合，再上皮上皮化，皮肤组织结构，炎性细胞浸润性和分子生物标志物表达所证明的。拉塞尔的研究为ASC疗法的临床翻译和调节批准铺平了道路。虽然可以很好地确定预防压力溃疡需要劳动密集型护理，但辅助生活中心和护士屋的患者仍处于患压疮的高风险。超过70％的压力溃疡发生在70岁以上的美国人中，他们的医院费用每年超过110亿美元。当前压力溃疡的治疗主要依赖于手术调试，高压氧和负压装置。脂肪衍生的基于细胞的疗法有可能大大降低高速溃疡患者的住院时间和相关的医疗保健费用。 Lacell已与Tissue Genesis，Inc。合作，使用其已建立的Icellator装置获得临床级人类SVF细胞。这种战略合作伙伴关系将加速Lacell的细胞疗法到市场的临床翻译。具体目的（SA）将解决鼠模型中的药物毒理学调节问题，并在SVF细胞（SA1）（SA1）（SA2）的情况下，是对研究装置豁免的食品药品监督管理机构的确定性方案。每个SA将评估人类SVF细胞和ASC在两性的免疫缺陷和免疫能力小鼠中的鼠压力溃疡治疗方面的浓度依赖性；将评估年轻人和老年免疫能力的小鼠。单独注射PBS或用人真皮成纤维细胞注射为阴性对照，而FDA批准的糖尿病伤口疗法的局部应用Beclapermin（PDGF-BB）将作为阳性对照。定量结果将包括伤口闭合率，炎症细胞浸润，促炎性细胞因子表达以及对原位人类细胞的免疫组织化学检测。由于压力溃疡治疗占医疗保健总预算的1-4％开发国家，拉莱尔的发展技术已经考虑了市场潜力。