Adipose vs Bone Marrow Derived Stromal cells for Treatment of Stroke in the Aged

脂肪与骨髓基质细胞治疗老年人中风的比较

• 批准号: 7107641
• 负责人: SMITA I SAVANT-BHONSALE
• 金额: $ 13.24万
• 依托单位: THERADIGM, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107641
• 关键词: adipose tissue; alkaline phosphatase; animal old age; biomarker; brain; cell population study; chemotaxis; disease /disorder model; genetically modified animals; hematopoietic stem cells; histology; human therapy evaluation; immunocytochemistry; laboratory rat; neuroprotectants; nonhuman therapy evaluation; phenotype; stem cell transplantation; stroke therapy; stromal cells; therapy design /development; tissue /cell culture

DESCRIPTION (provided by applicant): Stroke is the leading cause of long term disability with majority of strokes occuring in the aged. There is a great need for therapies that can reduce neurological deficits from stroke and extend the healthy, active years of life of the affected patients. Thus the long term objective of this proposal is to develop a cellular therapeutic product that can be administered beyond the acute period after stroke for the purpose of restoring neurological function. Adult Bone Marrow derived Stromal/Stem Cells (BMSCs) have been shown to improve neurological function in animal models of stroke and a recent small clinical trial, even when the cells were administered well beyond the 3 hour window mandated for currently approved treatments of stroke patients. Adipose derived Stromal/Stem cells (ASCs) are similar to BMSCs in some ways but unique in other ways, and can be easily isolated in large quantities from lipoaspirates obtained during elective liposuction procedures. Theradigm has gained both the knowledge and intellectual property to produce and use both BMSCs and ASCs for the treatment of neurological diseases. We hypothesize that ASCs will display greater efficacy relative to BMSCs for treatment of stroke. In this Phase-1 proposal ASCs and BMSCs will be isolated from transgenic rats expressing a human alkaline phosphatase (AP) marker. The cells will be delivered intravenously to aged rats subjected to stroke to determine which cell type is more efficacious in improving neurological function after stroke. The distribution of the transplanted cells in the brain will be assessed histologically using the AP marker. Additionally, migration of ASCs or BMSCs towards components of ischemic brain tissue obtained from rats at various time points after stroke will be measured in vitro to determine the optimal therapeutic window for delivering the cells, which can be subsequently confirmed in the rat stroke model with the chosen cell type. Results from this Phase-1 study will be used in Phase-2 to further investigate either human ASCs or human BMSCs in suitable animal models in terms of both efficacy and safety, along with process development for manufacture of large scale clinical grade human cells. Adult derived cells such as ASCs and BMSCs that are immunologically inert could potentially be developed into an off the shelf product that can improve the quality of life of millions of stroke survivors living with a wide range of neurological deficits.

描述（由申请人提供）：中风是导致长期残疾的主要原因，其中大多数发生在老年人身上。我们迫切需要一种治疗方法，可以减少中风造成的神经功能缺陷，延长受影响患者的健康、活跃的生活时间。因此，这项建议的长期目标是开发一种细胞治疗产品，可以在中风后的急性期以外进行管理，以恢复神经功能。在中风动物模型和最近的一项小型临床试验中，成人骨髓来源基质/干细胞（BMSCs）已被证明可以改善神经功能，即使这些细胞的使用时间远远超过目前批准的中风患者治疗规定的3小时。脂肪源性基质/干细胞（ASCs）在某些方面与骨髓间充质干细胞相似，但在其他方面又很独特，可以很容易地从选择性抽脂过程中获得的抽脂物中大量分离出来。Theradigm已经获得了生产和使用骨髓间充质干细胞和造血干细胞治疗神经系统疾病的知识和知识产权。我们假设ASCs相对于骨髓间充质干细胞在治疗中风方面表现出更大的疗效。在这个第一阶段的提议中，ASCs和BMSCs将从表达人碱性磷酸酶（AP）标记的转基因大鼠中分离出来。这些细胞将被静脉注射到中风的老年大鼠体内，以确定哪种细胞类型在改善中风后的神经功能方面更有效。使用AP标记物对移植细胞在脑内的分布进行组织学评估。此外，将在体外测量脑卒中后不同时间点ASCs或BMSCs向大鼠缺血脑组织组分的迁移，以确定输送细胞的最佳治疗窗口，随后可在具有所选细胞类型的大鼠脑卒中模型中证实。第一阶段研究的结果将用于第二阶段，在合适的动物模型中进一步研究人类ASCs或人骨髓间充质干细胞的有效性和安全性，以及大规模临床级人类细胞制造的工艺开发。免疫惰性的成体衍生细胞，如ASCs和骨髓间充质干细胞，可能被开发成一种现成的产品，可以改善数百万患有各种神经功能缺陷的中风幸存者的生活质量。