A Novel Method to Improve Proliferation and Neural Induction of Human MSCs

一种改善人类间充质干细胞增殖和神经诱导的新方法

• 批准号: 8315667
• 负责人: Bradley H. Garcia
• 金额: $ 34.47万
• 依托单位: PRIMORIGEN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2014-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8315667
• 关键词: Address; Amyotrophic Lateral Sclerosis; Animal Model; Astrocytes; Autologous; Back; Basic Science; Biological Markers; Bone Marrow; Carbohydrates; Cardiovascular Diseases; Cell Culture Techniques; Cell physiology; Cells; Clinical; Clinical Trials; Crowding; Culture Media; Deposition; Diabetes Mellitus; Differentiation and Growth; Disease; Disease model; Environment; Evaluation; Extracellular Matrix; Goals; Government; Harvest; Human; In Vitro; Investments; Legal patent; Limb structure; Measures; Mesenchymal Stem Cells; Methodology; Methods; Metric; Modeling; Motor; Neurodegenerative Disorders; Outcome; Parkinson Disease; Patients; Persons; Phase; Phenotype; Plastics; Population; Property; Protocols documentation; Publishing; Rattus; Research; Sensory; Skeleton; Small Business Innovation Research Grant; Solutions; Spinal cord injury; Techniques; Technology; Testing; Therapeutic; Therapeutic Effect; Time; Transplantation; Work; aqueous; base; cell type; clinical application; clinically relevant; design; human stem cells; improved; in vivo; interest; macromolecule; new technology; novel; phase 1 study; phase 2 study; pre-clinical research; preclinical study; relating to nervous system; research and development; spinal cord and brain injury; stem cell differentiation; therapeutic effectiveness

DESCRIPTION (provided by applicant): Primorigen Biosciences will develop an enhanced cell culturing technology that dramatically increases proliferative and differentiation capabilities of human bone-marrow derived mesenchymal stem cells (hMSC's) for neural induction, and ultimately for induction to other lineages for research and clinical applications. The technology consists of proprietary cell culture media additives that effectively recreate native biophysical properties of the cellular microenvironment and encourage cells to secrete and remodel extracellular matrix (ECM) using their own endogenous machinery. The net effect is to dramatically enhance proliferation and differentiation capacity. Phase I studies will assess feasibility by determining whether the proprietary additives improve expansion and neural induction of hMSCs under prolonged passaging (10+) as measured by biomarker profiling and efficacy after transplant into SCI animal models. Phase II studies will focus on increasing MMC-driven hMSC expansion and extending the Phase I studies to extending the Phase I studies to include induction, transplantation, and testing of hMSCs in additional neurodegenerative disease models, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. The new technology will be commercialized globally through Primorigen's own direct network of customers and through its major strategic partners. PUBLIC HEALTH RELEVANCE: The last two decades have seen an overwhelming amount of basic and preclinical research demonstrating the therapeutic promise of human mesenchymal stem cells (hMSCs) for neurodegenerative diseases, spinal cord and brain injuries, cardiovascular diseases, diabetes mellitus, and diseases of the skeleton. In most of these studies, treatment with hMSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide. To obtain sufficient hMSCs for these autologous clinical applications, the hMSCs must be harvested from the patient and quickly expanded in vitro before transplantation back to the patient. Recent studies suggest that neural induction of hMSCs (NI-hMSCs) prior to transplantation could provide a significant advantage over naive hMSC in treatment of animal models of spinal cord injury (SCI). Furthermore, recent studies by our collaborators reveal that the hMSCs expanded using standard cell culturing conditions lose their ability to generate NI-hMSCs after 4 passages, far short of the estimated expansion required to generate sufficient cell populations for clinical therapy. To address this problem, we have devised a proprietary, patent-pending cell culturing technology to effectively recreate native biophysical properties of the cellular microenvironment that encourages cells to secrete and remodel extracellular matrix (ECM) using their own endogenous machinery as a solution for increasing proliferation rates and maintaining differentiation capacity over a sufficient number of passages to generate the cells needed for therapeutic applications.

描述（由申请人提供）：Primorigen Biosciences将开发一种增强的细胞培养技术，该技术可显著提高人骨髓间充质干细胞（hMSC）的增殖和分化能力，用于神经诱导，并最终诱导为其他谱系，用于研究和临床应用。该技术由专有的细胞培养基添加剂组成，可有效地重建细胞微环境的天然生物物理特性，并鼓励细胞利用自身的内源性机制分泌和重塑细胞外基质（ECM）。净效应是显著增强增殖和分化能力。I期研究将通过确定专有添加剂是否在移植到SCI动物模型中后通过生物标志物分析和功效测量的延长传代（10+）下改善hMSC的扩增和神经诱导来评估可行性。II期研究将重点关注增加MMC驱动的hMSC扩增，并将I期研究扩展到包括在其他神经退行性疾病模型（如肌萎缩侧索硬化症（ALS）和帕金森病）中诱导，移植和测试hMSC。这项新技术将通过Primorigen自己的直接客户网络和主要战略合作伙伴在全球范围内商业化。 公共卫生相关性：在过去的二十年里，大量的基础和临床前研究证明了人间充质干细胞（hMSCs）对神经退行性疾病，脊髓和脑损伤，心血管疾病，糖尿病和骨骼疾病的治疗前景。在大多数这些研究中，用hMSC治疗产生了实质性的功能益处，并且这些临床前研究已经导致在世界范围内启动了许多临床试验。为了获得足够的hMSC用于这些自体临床应用，必须从患者中收获hMSC并在移植回患者之前在体外快速扩增。最近的研究表明，神经诱导的hMSC（NI-hMSC）移植前可以提供一个显着的优势，幼稚的hMSC在治疗脊髓损伤（SCI）的动物模型。此外，我们的合作者最近的研究表明，使用标准细胞培养条件扩增的hMSC在4次传代后失去了产生NI-hMSC的能力，远远低于产生足够的细胞群用于临床治疗所需的估计扩增。为了解决这个问题，我们已经设计了一种专有的、正在申请专利的细胞培养技术，以有效地重建细胞微环境的天然生物物理特性，该细胞微环境鼓励细胞使用其自身的内源性机制分泌和重塑细胞外基质（ECM），作为在足够数量的传代中增加增殖速率和维持分化能力以产生治疗应用所需的细胞的解决方案。