The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural stem cells. In order to improve post-injury neuronal differentiation and/or maturation potential, cell-cell and cell-biochemical interactions have been investigated. However, little is known about the role of stem cell-matrix interactions on stem cell-mediated repair. Here, we specifically examined the effects of matrix elasticity on stem cell-mediated repair in the spinal cord, since spinal cord injury results in drastic changes in parenchyma elasticity and viscosity. Spinal cord-derived neural precursor cells (NPCs) were grown on bis-acrylamide substrates with various rigidities. NPC growth, proliferation, and differentiation were examined and optimal in the range of normal spinal cord elasticity. In conclusion, limitations in NPC growth, proliferation, and neuronal differentiation were encountered when substrate elasticity was not within normal spinal cord tissue elasticity ranges. These studies elucidate the effect injury mediated mechanical changes may have on tissue repair by stem cells. Furthermore, this information can be applied to the development of future neuroregenerative biomaterials for spinal cord repair.

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Numerous stem cells therapies have been studied for the replacement of damaged neurons due to spinal cord injury. Our laboratory’s goal is to design an implantable platform for spinal cord neuron (SCN) proliferation and differentiation in order to replace damaged neurons in the injured spinal cord. Based on previous literature, we suspect we can promote neuronal precursor cell (NPC) proliferation and differentiation utilizing elastic matrices.

Glioblastoma (GB) is the most common and aggressive form of malignant primary brain tumors in adults. Immunotherapeutics are a promising avenue of treatment, but their effectiveness can improve if we further understand the immune system's role in tumor progression. The tumor extracellular matrix (ECM) and tumor-associated macrophages promote tumor growth and invasion, but the effect of the tumor ECM on macrophage activity is unknown. We hypothesize that the physical and biological properties of the tumor ECM drive macrophage phenotypes that promote tumor growth. In this study, we investigated the ECM-macrophage interface from both a biological and physical perspective. We found that tumor ECM stiffness and composition promoted the proinflammatory activity of macrophages in short-term cultures. This is surprising considering most investigators have found that macrophages have anti-inflammatory activity in mouse tumors. We also examined whether proinflammatory mediators were present in GB tumors. We found that TNF-alpha, a proinflammatory cytokine, was present in 7 out of 7 tumors of patients with GB. Also, we found that IL-10, an anti-inflammatory cytokine, was present in 6 out of 6 tumors of patients with GB. Our results show a need to clinically define the inflammatory activity in the tumor microenvironment and identify the mechanisms that drive inflammation.