ASC101 Enhancement of Regenerative Capacity of Amniotic Fluid-derived Stem Cells

ASC101增强羊水干细胞的再生能力

基本信息

批准号：
8253016
负责人：
LEONARD P MILLER
金额：
$ 15.68万
依托单位：
TARGAZYME, INC.
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：
2012-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8253016
关键词：
Address Affect Americas Amniotic Fluid Anatomy Animal Disease Models Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Area Bathing Beds Blood Circulation Blood Vessels Bone Marrow Burn injury Cell Therapy Cells Centers for Disease Control and Prevention (U.S.)Clinical Contralateral Contusions Crush Injury Development Disease Dose Environment Evaluation Event Exhibits Fracture Functional disorder Gene Expression Harvest Hematopoietic Hemorrhage Histologic Homing Human Immune In Vitro Injection of therapeutic agent Injury Institutes Laboratories Lead Life Limb structure Malignant - descriptor Measurement Mediating Medicine Mesenchymal Stem Cells Modeling Multiple Trauma Mus Muscle Muscle function Musculoskeletal Diseases Operative Surgical Procedures Organ Pharmacologic Substance Physiological Population Process Rattus Recovery Recovery of Function Regenerative Medicine Reporting Residencies Selectins Site Skeletal Muscle Small Business Technology Transfer Research Solutions Stem cells Syndrome Technology Teratoma Testing Therapeutic Time Tissues Trauma United States adult stem cell amniotic fluid derived stem cell base cell motility cost disability forest improved injured new technology novel novel strategies pre-clinical regenerative relating to nervous system repaired research study stem cell population

项目摘要

DESCRIPTION (provided by applicant): In the present STTR we propose to investigate two novel approaches in our exploration of the therapeutic and regenerative potential of cell-based medicine. Furthermore, we will utilize a preclinical animal model of compression syndrome (CS) that mimics the pathophysiology of multiple injuries such as crush injuries, burns, circulation blockage, fractures, hemorrhage, severely bruised muscles, surgery and other trauma which lead to devastating tissue damage with potential loss of limb or life. These injuries result in damage to the muscular, neural and vascular components of the skeletal muscle compartment. We will examine amniotic fluid-derived (AFS) stem cells in combination with ASC101 in this small animal CS model. The important features of AFS cells that underscore their therapeutic potential include (1) ability to be expanded to a greater extent than other adult stem cells, (2) anti-inflammatory and (3) have multipotential differentiation capabilities but (4) do not show signs of malignant transformation in culture or form teratomas. The development of these novel stem cells has been pioneered by Dr. Soker and his colleagues at the Wake Forest Institute of Regenerative Medicine for the past 10 years. ASC101 is a new technology developed by America Stem Cell (ASC). ASC has shown the ability for ASC101 treatment to enhance selectin-mediated homing of specific stem cells to the bone marrow and ischemic tissue bed. Use of this technology involves a simple incubation of the stem cells with ASC101 just prior to injection. Our presently proposed studies are divided into two Specific Aims (SA). In SA#1 we will identify the parameters required for optimal delivery of AFS cells to the damaged tissue and assess whether ASC101 enhances cell homing. These parameters include time of injection post injury, optimal dose and residency time of the injected stem cells in the damaged tissue. In SA#2 we will utilize these parameters in a CS model that mimics the pathophysiology of multiple injuries. We will conduct not only anatomical analyses of various cell populations in the injured area post trauma but also functional tests to assess muscle functional recovery. The successful implementation of ASC101 with AFS cells to treat injuries associated with CS would be directly relevant to improving our understanding of the muscle recovery processes that occur following multiple types of injuries. In addition, the combination of ASC101 with AFS cells could enhance the therapeutic and regenerative capacity of these cells and most importantly provide an off-the shelf, effective solution for tissue damage due to multiple types of injuries or diseases. PUBLIC HEALTH RELEVANCE: A variety of injuries, such as crush injuries, burns, circulation blockage, fractures, hemorrhage, severely bruised muscles, surgery and other trauma lead to devastating tissue damage with potential loss of limb or life. To address the complexity of the events underlying the pathophysiology of these injuries we will explore the therapeutic potential of a cell-based approach. We will utilize a novel type of stem cell exhibiting multilineage differentiation potential in combination with a novel technology that can enhance the migration of cells to the site of damage. The potential for broad therapeutic application of this combination approach underscores the importance of these proposed studies.

描述（由申请人提供）：在本 STTR 中，我们建议在探索细胞医学的治疗和再生潜力时研究两种新方法。此外，我们将利用压缩综合征（CS）的临床前动物模型，模拟多种损伤的病理生理学，例如挤压伤、烧伤、循环阻塞、骨折、出血、肌肉严重擦伤、手术和其他导致破坏性组织损伤的创伤可能会失去肢体或生命。这些损伤会导致骨骼肌室的肌肉、神经和血管成分受损。我们将在这个小动物 CS 模型中检查羊水源性 (AFS) 干细胞与 ASC101 的结合。 AFS 细胞强调其治疗潜力的重要特征包括（1）比其他成体干细胞具有更大程度的扩增能力，（2）抗炎性和（3）具有多向分化能力，但（4）不显示培养中恶性转化的迹象或形成畸胎瘤。过去 10 年来，维克森林再生医学研究所的 Soker 博士及其同事率先开发了这些新型干细胞。 ASC101是美国干细胞公司（ASC）开发的一项新技术。 ASC 已显示出 ASC101 治疗能够增强选择素介导的特定干细胞归巢至骨髓和缺血组织床的能力。使用该技术需要在注射前将干细胞与 ASC101 进行简单的孵育。我们目前提出的研究分为两个具体目标（SA）。在 SA#1 中，我们将确定将 AFS 细胞最佳递送至受损组织所需的参数，并评估 ASC101 是否增强细胞归巢。这些参数包括损伤后注射时间、注射干细胞在受损组织中的最佳剂量和停留时间。在 SA#2 中，我们将在模拟多重损伤的病理生理学的 CS 模型中利用这些参数。我们不仅会对创伤后受伤区域的各种细胞群进行解剖分析，还会进行功能测试以评估肌肉功能恢复情况。使用 AFS 细胞成功实施 ASC101 来治疗 CS 相关损伤，将直接关系到提高我们对多种类型损伤后发生的肌肉恢复过程的理解。此外，ASC101与AFS细胞的组合可以增强这些细胞的治疗和再生能力，最重要的是，为多种类型的损伤或疾病引起的组织损伤提供现成的有效解决方案。公众健康相关性：各种伤害，如挤压伤、烧伤、循环阻塞、骨折、出血、肌肉严重擦伤、手术和其他创伤，会导致毁灭性的组织损伤，可能导致肢体或生命丧失。为了解决这些损伤病理生理学背后事件的复杂性，我们将探索基于细胞的方法的治疗潜力。我们将利用一种具有多谱系分化潜力的新型干细胞，结合一种可以增强细胞向损伤部位迁移的新技术。这种组合方法的广泛治疗应用的潜力强调了这些拟议研究的重要性。