I-Corps: Accelerating discovery research into neural-stem-cell-driven tissue regrowth through modeling and simulation

这个I-Corps项目的更广泛的影响/商业潜力是定义用于药物开发和/或组织修复干预策略的建模和仿真平台的要求。这些策略可能比目前通过应用实验方法获得的更具预测性和效率。最终，该工具的目标是使因创伤性脑损伤、脊髓损伤或中风而失去的神经组织再生成为可能。实现这一目标可能会改变数百万患者及其家属的生活，同时也会大大减轻社会的经济负担。翻译后的平台将为制药和生物技术公司临床前（发现）研究部门的科学家提供量身定制的服务。通过提供干细胞驱动组织再生建模领域的专业知识，客户将能够缩小潜在有效化合物或干预策略的范围，使其成为最有可能成功的治疗方法。这种策略可以加速发现过程，同时减少研发的成本和时间。这个I-Corps项目是基于推进神经组织修复药物发现平台的数学和计算模型的发展。通过全面的细胞生物学数据集，这些模型模拟了大脑和脊髓正常发育过程中干细胞驱动组织生长的动态。此外，该模型还模拟了创伤性脑损伤、脊髓损伤和中风后中枢神经系统的再生反应。近年来，有希望的治疗策略已经被开发出来，以促进组织再生，包括活化成体神经干细胞固有的病人的中枢神经系统，以及移植外源性神经干细胞到细胞丢失的部位。为开发此类干预策略而选择和设计测试目前是基于“试错法”。然而，由于成功的结构再生和功能恢复所涉及的生物因素和过程的复杂性，这种方法消耗了大量的资源，并限制了有效治疗策略的发现。这个过程可以通过建模和模拟来简化。这种策略可以帮助科学家选择最有意义的实验，从而减少与实验室工作相关的时间和成本，同时提高研究质量。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is to define the requirements of modeling and simulation platforms for drug development and/or intervention strategies used in tissue repair. These strategies may be more predictive and efficient than currently available through application of experimental approaches. Ultimately, the goal for this tool is to make possible regeneration of neural tissue lost to traumatic brain injury, spinal cord injury, or stroke. Reaching this goal may transform the lives of millions of patients and their families while also substantially reducing the financial burdens to society. The translation will offer the platform as a service tailored to the needs of scientists in preclinical (discovery) research departments of pharmaceutical and biotech companies. By providing domain expertise in the modeling of stem-cell-driven tissue regeneration, clients will be enabled to narrow down the range of potentially effective compounds or intervention strategies to those treatments with the highest probability to succeed. This strategy could accelerate the discovery process, while reducing the costs and time involved in research and development.This I-Corps project is based on advancing the development of mathematical and computational models for a drug discovery platform aimed at neural tissue repair. Informed by comprehensive cell-biological data sets, these models simulate the dynamics of stem cell-driven tissue growth during the normal development of the brain and spinal cord. In addition, the models simulate the regenerative response of the central nervous system after traumatic brain injury, spinal cord injury, and stroke. In recent years, promising therapeutic strategies have been developed to promote tissue regrowth, including activation of adult neural stem cells intrinsic to the patient’s central nervous system, and the transplantation of extrinsic neural stem cells to the site of cell loss. The selection and design of tests for development of such intervention strategies is currently based on “trial and error.” However, due to the complexity of biological factors and processes involved in successful structural regeneration and functional recovery, this approach consumes considerable resources and curtails progress in the discovery of effective treatment strategies. This process may be streamlined by employing modeling and simulations. Such a strategy may help scientists to select the most meaningful experiments, thereby reducing time and costs associated with lab work, while at the same time raising the quality of the research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.